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HIV molecular biology
BTY328 Virology wstafforduwcacza
Retroviruses
Oncoviruses cancer causing eg HTLV Lentiviruses slow virus diseases eg HIV-1
and HIV-2 Spumaviruses not associated with human
disease Retroviruses such as HIV are so named
because they reverse the usual flow of genetic information within host cell in order to reproduce themselves (Central dogma DNA-RNA-protein)
Reverse transcriptase and HIV integration into the host genome
Retroviral RNA is copied using the enzyme reverse transcriptase (RT) into a complementary DNA strand this is copied into dsDNA and this migrates to the host nucleus and becomes integrated into the host cell DNA as a provirusFrom this point on the process is irreversible as the viral genes are part of the cells genetic information (essentially an acquired genetic disease)
Active and latent HIV infection of CD4
HIV recognition of CD4 T-cell
Recognition attachment
HIV surface membrane has glycoproteins gp41 and gp120
1048698 gp120 binds to CD4 receptor on CD4+ cell (T lymphocytes)
1048698 gp41 binds to a cytokine receptor either CCR5 or CXCR4 fusing viral envelope with cell membrane and releases the capsid into the cell
Reverse transcription and integration into the host genome
Nucleocapsid contains two single stranded RNA molecules as well as reverse transcriptase which makes dsDNA from the RNA
1048698 dsDNA is transported to nucleus by viral protein R (VPR)
1048698 HIV integrase iserts viral dsDNA into host cell
HIV genome replication and protein production
Incorporated viral DNA is transcribed onto two mRNAs
1048698 one strand contains information for HIV structural proteins
1048698 other serves as genetic material of new virus
Translated polypeptide is cleaved by protease making functional HIV proteins
Assembly of HIV particles
HIV Structural proteins spontaneously assemble
around RNA and viral proteins forming new virus
1048698 Virus is encapsulated by cell membrane and buds off (exocytosis)
1048698 Through mechanisms not understood (adoptosis) host cells die
HI V genome replication
Reverse transcriptase (RT)
Reverse Transcriptase Heterodimer consisting of a full 66kDa RT monomer with RNaseH domain and a 51kDa RT monomer from which the RNaseH domain has been cleaved
HIV RT is a RNA-dependant DNA polymerase transcribing ssDNA from RNA template
It has a subunit with RNaseH activity- hydrolysing the retroviral RNA from the RNA-DNA complex
Also acts as a DNA-dependant polymerase to transcribe the second DNA strand complementary to the first DNA strand
Integration in to the host genomeIntegration in to the host genome
HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product and is an attractive target for new anti-HIV drugs
Integrase catalyzes two reactions 3-end processing in which two
deoxynucleotides are removed from the 3 ends of the viral DNA
the strand transfer reaction in which the processed 3 ends of the viral DNA are covalently ligated to the host chromosomal DNA
Integrase is a key step in allowing viral DNA to become a permanent member of the host genome
Production of Viral RNA transcriptsProduction of Viral RNA transcripts
Before HIVs provirus genes can be expressed RNA copies that can be read by host cells protein-making machinery must be producedProviral DNA produces new strands of RNA some behave like mRNA to produce proteins essential for HIV production others become encased with viral core proteins to become new viruses
HIV genes
All retroviruses contain RNA sequences that code for same three genes Flanking these genes is a sequence of similar nucleotides (LTRs)The LTR functions as a promoter5ndashLTR-- GAG POL ENV ndashLTR--3
There are 9 HIV genes encoding proteinsStructural proteins GAG POL and ENVRegulatory proteins Tat and RevAccessory proteins Nef Vif Vpu Vpr
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
Retroviruses
Oncoviruses cancer causing eg HTLV Lentiviruses slow virus diseases eg HIV-1
and HIV-2 Spumaviruses not associated with human
disease Retroviruses such as HIV are so named
because they reverse the usual flow of genetic information within host cell in order to reproduce themselves (Central dogma DNA-RNA-protein)
Reverse transcriptase and HIV integration into the host genome
Retroviral RNA is copied using the enzyme reverse transcriptase (RT) into a complementary DNA strand this is copied into dsDNA and this migrates to the host nucleus and becomes integrated into the host cell DNA as a provirusFrom this point on the process is irreversible as the viral genes are part of the cells genetic information (essentially an acquired genetic disease)
Active and latent HIV infection of CD4
HIV recognition of CD4 T-cell
Recognition attachment
HIV surface membrane has glycoproteins gp41 and gp120
1048698 gp120 binds to CD4 receptor on CD4+ cell (T lymphocytes)
1048698 gp41 binds to a cytokine receptor either CCR5 or CXCR4 fusing viral envelope with cell membrane and releases the capsid into the cell
Reverse transcription and integration into the host genome
Nucleocapsid contains two single stranded RNA molecules as well as reverse transcriptase which makes dsDNA from the RNA
1048698 dsDNA is transported to nucleus by viral protein R (VPR)
1048698 HIV integrase iserts viral dsDNA into host cell
HIV genome replication and protein production
Incorporated viral DNA is transcribed onto two mRNAs
1048698 one strand contains information for HIV structural proteins
1048698 other serves as genetic material of new virus
Translated polypeptide is cleaved by protease making functional HIV proteins
Assembly of HIV particles
HIV Structural proteins spontaneously assemble
around RNA and viral proteins forming new virus
1048698 Virus is encapsulated by cell membrane and buds off (exocytosis)
1048698 Through mechanisms not understood (adoptosis) host cells die
HI V genome replication
Reverse transcriptase (RT)
Reverse Transcriptase Heterodimer consisting of a full 66kDa RT monomer with RNaseH domain and a 51kDa RT monomer from which the RNaseH domain has been cleaved
HIV RT is a RNA-dependant DNA polymerase transcribing ssDNA from RNA template
It has a subunit with RNaseH activity- hydrolysing the retroviral RNA from the RNA-DNA complex
Also acts as a DNA-dependant polymerase to transcribe the second DNA strand complementary to the first DNA strand
Integration in to the host genomeIntegration in to the host genome
HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product and is an attractive target for new anti-HIV drugs
Integrase catalyzes two reactions 3-end processing in which two
deoxynucleotides are removed from the 3 ends of the viral DNA
the strand transfer reaction in which the processed 3 ends of the viral DNA are covalently ligated to the host chromosomal DNA
Integrase is a key step in allowing viral DNA to become a permanent member of the host genome
Production of Viral RNA transcriptsProduction of Viral RNA transcripts
Before HIVs provirus genes can be expressed RNA copies that can be read by host cells protein-making machinery must be producedProviral DNA produces new strands of RNA some behave like mRNA to produce proteins essential for HIV production others become encased with viral core proteins to become new viruses
HIV genes
All retroviruses contain RNA sequences that code for same three genes Flanking these genes is a sequence of similar nucleotides (LTRs)The LTR functions as a promoter5ndashLTR-- GAG POL ENV ndashLTR--3
There are 9 HIV genes encoding proteinsStructural proteins GAG POL and ENVRegulatory proteins Tat and RevAccessory proteins Nef Vif Vpu Vpr
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
Reverse transcriptase and HIV integration into the host genome
Retroviral RNA is copied using the enzyme reverse transcriptase (RT) into a complementary DNA strand this is copied into dsDNA and this migrates to the host nucleus and becomes integrated into the host cell DNA as a provirusFrom this point on the process is irreversible as the viral genes are part of the cells genetic information (essentially an acquired genetic disease)
Active and latent HIV infection of CD4
HIV recognition of CD4 T-cell
Recognition attachment
HIV surface membrane has glycoproteins gp41 and gp120
1048698 gp120 binds to CD4 receptor on CD4+ cell (T lymphocytes)
1048698 gp41 binds to a cytokine receptor either CCR5 or CXCR4 fusing viral envelope with cell membrane and releases the capsid into the cell
Reverse transcription and integration into the host genome
Nucleocapsid contains two single stranded RNA molecules as well as reverse transcriptase which makes dsDNA from the RNA
1048698 dsDNA is transported to nucleus by viral protein R (VPR)
1048698 HIV integrase iserts viral dsDNA into host cell
HIV genome replication and protein production
Incorporated viral DNA is transcribed onto two mRNAs
1048698 one strand contains information for HIV structural proteins
1048698 other serves as genetic material of new virus
Translated polypeptide is cleaved by protease making functional HIV proteins
Assembly of HIV particles
HIV Structural proteins spontaneously assemble
around RNA and viral proteins forming new virus
1048698 Virus is encapsulated by cell membrane and buds off (exocytosis)
1048698 Through mechanisms not understood (adoptosis) host cells die
HI V genome replication
Reverse transcriptase (RT)
Reverse Transcriptase Heterodimer consisting of a full 66kDa RT monomer with RNaseH domain and a 51kDa RT monomer from which the RNaseH domain has been cleaved
HIV RT is a RNA-dependant DNA polymerase transcribing ssDNA from RNA template
It has a subunit with RNaseH activity- hydrolysing the retroviral RNA from the RNA-DNA complex
Also acts as a DNA-dependant polymerase to transcribe the second DNA strand complementary to the first DNA strand
Integration in to the host genomeIntegration in to the host genome
HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product and is an attractive target for new anti-HIV drugs
Integrase catalyzes two reactions 3-end processing in which two
deoxynucleotides are removed from the 3 ends of the viral DNA
the strand transfer reaction in which the processed 3 ends of the viral DNA are covalently ligated to the host chromosomal DNA
Integrase is a key step in allowing viral DNA to become a permanent member of the host genome
Production of Viral RNA transcriptsProduction of Viral RNA transcripts
Before HIVs provirus genes can be expressed RNA copies that can be read by host cells protein-making machinery must be producedProviral DNA produces new strands of RNA some behave like mRNA to produce proteins essential for HIV production others become encased with viral core proteins to become new viruses
HIV genes
All retroviruses contain RNA sequences that code for same three genes Flanking these genes is a sequence of similar nucleotides (LTRs)The LTR functions as a promoter5ndashLTR-- GAG POL ENV ndashLTR--3
There are 9 HIV genes encoding proteinsStructural proteins GAG POL and ENVRegulatory proteins Tat and RevAccessory proteins Nef Vif Vpu Vpr
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
Active and latent HIV infection of CD4
HIV recognition of CD4 T-cell
Recognition attachment
HIV surface membrane has glycoproteins gp41 and gp120
1048698 gp120 binds to CD4 receptor on CD4+ cell (T lymphocytes)
1048698 gp41 binds to a cytokine receptor either CCR5 or CXCR4 fusing viral envelope with cell membrane and releases the capsid into the cell
Reverse transcription and integration into the host genome
Nucleocapsid contains two single stranded RNA molecules as well as reverse transcriptase which makes dsDNA from the RNA
1048698 dsDNA is transported to nucleus by viral protein R (VPR)
1048698 HIV integrase iserts viral dsDNA into host cell
HIV genome replication and protein production
Incorporated viral DNA is transcribed onto two mRNAs
1048698 one strand contains information for HIV structural proteins
1048698 other serves as genetic material of new virus
Translated polypeptide is cleaved by protease making functional HIV proteins
Assembly of HIV particles
HIV Structural proteins spontaneously assemble
around RNA and viral proteins forming new virus
1048698 Virus is encapsulated by cell membrane and buds off (exocytosis)
1048698 Through mechanisms not understood (adoptosis) host cells die
HI V genome replication
Reverse transcriptase (RT)
Reverse Transcriptase Heterodimer consisting of a full 66kDa RT monomer with RNaseH domain and a 51kDa RT monomer from which the RNaseH domain has been cleaved
HIV RT is a RNA-dependant DNA polymerase transcribing ssDNA from RNA template
It has a subunit with RNaseH activity- hydrolysing the retroviral RNA from the RNA-DNA complex
Also acts as a DNA-dependant polymerase to transcribe the second DNA strand complementary to the first DNA strand
Integration in to the host genomeIntegration in to the host genome
HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product and is an attractive target for new anti-HIV drugs
Integrase catalyzes two reactions 3-end processing in which two
deoxynucleotides are removed from the 3 ends of the viral DNA
the strand transfer reaction in which the processed 3 ends of the viral DNA are covalently ligated to the host chromosomal DNA
Integrase is a key step in allowing viral DNA to become a permanent member of the host genome
Production of Viral RNA transcriptsProduction of Viral RNA transcripts
Before HIVs provirus genes can be expressed RNA copies that can be read by host cells protein-making machinery must be producedProviral DNA produces new strands of RNA some behave like mRNA to produce proteins essential for HIV production others become encased with viral core proteins to become new viruses
HIV genes
All retroviruses contain RNA sequences that code for same three genes Flanking these genes is a sequence of similar nucleotides (LTRs)The LTR functions as a promoter5ndashLTR-- GAG POL ENV ndashLTR--3
There are 9 HIV genes encoding proteinsStructural proteins GAG POL and ENVRegulatory proteins Tat and RevAccessory proteins Nef Vif Vpu Vpr
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
HIV recognition of CD4 T-cell
Recognition attachment
HIV surface membrane has glycoproteins gp41 and gp120
1048698 gp120 binds to CD4 receptor on CD4+ cell (T lymphocytes)
1048698 gp41 binds to a cytokine receptor either CCR5 or CXCR4 fusing viral envelope with cell membrane and releases the capsid into the cell
Reverse transcription and integration into the host genome
Nucleocapsid contains two single stranded RNA molecules as well as reverse transcriptase which makes dsDNA from the RNA
1048698 dsDNA is transported to nucleus by viral protein R (VPR)
1048698 HIV integrase iserts viral dsDNA into host cell
HIV genome replication and protein production
Incorporated viral DNA is transcribed onto two mRNAs
1048698 one strand contains information for HIV structural proteins
1048698 other serves as genetic material of new virus
Translated polypeptide is cleaved by protease making functional HIV proteins
Assembly of HIV particles
HIV Structural proteins spontaneously assemble
around RNA and viral proteins forming new virus
1048698 Virus is encapsulated by cell membrane and buds off (exocytosis)
1048698 Through mechanisms not understood (adoptosis) host cells die
HI V genome replication
Reverse transcriptase (RT)
Reverse Transcriptase Heterodimer consisting of a full 66kDa RT monomer with RNaseH domain and a 51kDa RT monomer from which the RNaseH domain has been cleaved
HIV RT is a RNA-dependant DNA polymerase transcribing ssDNA from RNA template
It has a subunit with RNaseH activity- hydrolysing the retroviral RNA from the RNA-DNA complex
Also acts as a DNA-dependant polymerase to transcribe the second DNA strand complementary to the first DNA strand
Integration in to the host genomeIntegration in to the host genome
HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product and is an attractive target for new anti-HIV drugs
Integrase catalyzes two reactions 3-end processing in which two
deoxynucleotides are removed from the 3 ends of the viral DNA
the strand transfer reaction in which the processed 3 ends of the viral DNA are covalently ligated to the host chromosomal DNA
Integrase is a key step in allowing viral DNA to become a permanent member of the host genome
Production of Viral RNA transcriptsProduction of Viral RNA transcripts
Before HIVs provirus genes can be expressed RNA copies that can be read by host cells protein-making machinery must be producedProviral DNA produces new strands of RNA some behave like mRNA to produce proteins essential for HIV production others become encased with viral core proteins to become new viruses
HIV genes
All retroviruses contain RNA sequences that code for same three genes Flanking these genes is a sequence of similar nucleotides (LTRs)The LTR functions as a promoter5ndashLTR-- GAG POL ENV ndashLTR--3
There are 9 HIV genes encoding proteinsStructural proteins GAG POL and ENVRegulatory proteins Tat and RevAccessory proteins Nef Vif Vpu Vpr
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
Recognition attachment
HIV surface membrane has glycoproteins gp41 and gp120
1048698 gp120 binds to CD4 receptor on CD4+ cell (T lymphocytes)
1048698 gp41 binds to a cytokine receptor either CCR5 or CXCR4 fusing viral envelope with cell membrane and releases the capsid into the cell
Reverse transcription and integration into the host genome
Nucleocapsid contains two single stranded RNA molecules as well as reverse transcriptase which makes dsDNA from the RNA
1048698 dsDNA is transported to nucleus by viral protein R (VPR)
1048698 HIV integrase iserts viral dsDNA into host cell
HIV genome replication and protein production
Incorporated viral DNA is transcribed onto two mRNAs
1048698 one strand contains information for HIV structural proteins
1048698 other serves as genetic material of new virus
Translated polypeptide is cleaved by protease making functional HIV proteins
Assembly of HIV particles
HIV Structural proteins spontaneously assemble
around RNA and viral proteins forming new virus
1048698 Virus is encapsulated by cell membrane and buds off (exocytosis)
1048698 Through mechanisms not understood (adoptosis) host cells die
HI V genome replication
Reverse transcriptase (RT)
Reverse Transcriptase Heterodimer consisting of a full 66kDa RT monomer with RNaseH domain and a 51kDa RT monomer from which the RNaseH domain has been cleaved
HIV RT is a RNA-dependant DNA polymerase transcribing ssDNA from RNA template
It has a subunit with RNaseH activity- hydrolysing the retroviral RNA from the RNA-DNA complex
Also acts as a DNA-dependant polymerase to transcribe the second DNA strand complementary to the first DNA strand
Integration in to the host genomeIntegration in to the host genome
HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product and is an attractive target for new anti-HIV drugs
Integrase catalyzes two reactions 3-end processing in which two
deoxynucleotides are removed from the 3 ends of the viral DNA
the strand transfer reaction in which the processed 3 ends of the viral DNA are covalently ligated to the host chromosomal DNA
Integrase is a key step in allowing viral DNA to become a permanent member of the host genome
Production of Viral RNA transcriptsProduction of Viral RNA transcripts
Before HIVs provirus genes can be expressed RNA copies that can be read by host cells protein-making machinery must be producedProviral DNA produces new strands of RNA some behave like mRNA to produce proteins essential for HIV production others become encased with viral core proteins to become new viruses
HIV genes
All retroviruses contain RNA sequences that code for same three genes Flanking these genes is a sequence of similar nucleotides (LTRs)The LTR functions as a promoter5ndashLTR-- GAG POL ENV ndashLTR--3
There are 9 HIV genes encoding proteinsStructural proteins GAG POL and ENVRegulatory proteins Tat and RevAccessory proteins Nef Vif Vpu Vpr
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
Reverse transcription and integration into the host genome
Nucleocapsid contains two single stranded RNA molecules as well as reverse transcriptase which makes dsDNA from the RNA
1048698 dsDNA is transported to nucleus by viral protein R (VPR)
1048698 HIV integrase iserts viral dsDNA into host cell
HIV genome replication and protein production
Incorporated viral DNA is transcribed onto two mRNAs
1048698 one strand contains information for HIV structural proteins
1048698 other serves as genetic material of new virus
Translated polypeptide is cleaved by protease making functional HIV proteins
Assembly of HIV particles
HIV Structural proteins spontaneously assemble
around RNA and viral proteins forming new virus
1048698 Virus is encapsulated by cell membrane and buds off (exocytosis)
1048698 Through mechanisms not understood (adoptosis) host cells die
HI V genome replication
Reverse transcriptase (RT)
Reverse Transcriptase Heterodimer consisting of a full 66kDa RT monomer with RNaseH domain and a 51kDa RT monomer from which the RNaseH domain has been cleaved
HIV RT is a RNA-dependant DNA polymerase transcribing ssDNA from RNA template
It has a subunit with RNaseH activity- hydrolysing the retroviral RNA from the RNA-DNA complex
Also acts as a DNA-dependant polymerase to transcribe the second DNA strand complementary to the first DNA strand
Integration in to the host genomeIntegration in to the host genome
HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product and is an attractive target for new anti-HIV drugs
Integrase catalyzes two reactions 3-end processing in which two
deoxynucleotides are removed from the 3 ends of the viral DNA
the strand transfer reaction in which the processed 3 ends of the viral DNA are covalently ligated to the host chromosomal DNA
Integrase is a key step in allowing viral DNA to become a permanent member of the host genome
Production of Viral RNA transcriptsProduction of Viral RNA transcripts
Before HIVs provirus genes can be expressed RNA copies that can be read by host cells protein-making machinery must be producedProviral DNA produces new strands of RNA some behave like mRNA to produce proteins essential for HIV production others become encased with viral core proteins to become new viruses
HIV genes
All retroviruses contain RNA sequences that code for same three genes Flanking these genes is a sequence of similar nucleotides (LTRs)The LTR functions as a promoter5ndashLTR-- GAG POL ENV ndashLTR--3
There are 9 HIV genes encoding proteinsStructural proteins GAG POL and ENVRegulatory proteins Tat and RevAccessory proteins Nef Vif Vpu Vpr
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
HIV genome replication and protein production
Incorporated viral DNA is transcribed onto two mRNAs
1048698 one strand contains information for HIV structural proteins
1048698 other serves as genetic material of new virus
Translated polypeptide is cleaved by protease making functional HIV proteins
Assembly of HIV particles
HIV Structural proteins spontaneously assemble
around RNA and viral proteins forming new virus
1048698 Virus is encapsulated by cell membrane and buds off (exocytosis)
1048698 Through mechanisms not understood (adoptosis) host cells die
HI V genome replication
Reverse transcriptase (RT)
Reverse Transcriptase Heterodimer consisting of a full 66kDa RT monomer with RNaseH domain and a 51kDa RT monomer from which the RNaseH domain has been cleaved
HIV RT is a RNA-dependant DNA polymerase transcribing ssDNA from RNA template
It has a subunit with RNaseH activity- hydrolysing the retroviral RNA from the RNA-DNA complex
Also acts as a DNA-dependant polymerase to transcribe the second DNA strand complementary to the first DNA strand
Integration in to the host genomeIntegration in to the host genome
HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product and is an attractive target for new anti-HIV drugs
Integrase catalyzes two reactions 3-end processing in which two
deoxynucleotides are removed from the 3 ends of the viral DNA
the strand transfer reaction in which the processed 3 ends of the viral DNA are covalently ligated to the host chromosomal DNA
Integrase is a key step in allowing viral DNA to become a permanent member of the host genome
Production of Viral RNA transcriptsProduction of Viral RNA transcripts
Before HIVs provirus genes can be expressed RNA copies that can be read by host cells protein-making machinery must be producedProviral DNA produces new strands of RNA some behave like mRNA to produce proteins essential for HIV production others become encased with viral core proteins to become new viruses
HIV genes
All retroviruses contain RNA sequences that code for same three genes Flanking these genes is a sequence of similar nucleotides (LTRs)The LTR functions as a promoter5ndashLTR-- GAG POL ENV ndashLTR--3
There are 9 HIV genes encoding proteinsStructural proteins GAG POL and ENVRegulatory proteins Tat and RevAccessory proteins Nef Vif Vpu Vpr
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
Assembly of HIV particles
HIV Structural proteins spontaneously assemble
around RNA and viral proteins forming new virus
1048698 Virus is encapsulated by cell membrane and buds off (exocytosis)
1048698 Through mechanisms not understood (adoptosis) host cells die
HI V genome replication
Reverse transcriptase (RT)
Reverse Transcriptase Heterodimer consisting of a full 66kDa RT monomer with RNaseH domain and a 51kDa RT monomer from which the RNaseH domain has been cleaved
HIV RT is a RNA-dependant DNA polymerase transcribing ssDNA from RNA template
It has a subunit with RNaseH activity- hydrolysing the retroviral RNA from the RNA-DNA complex
Also acts as a DNA-dependant polymerase to transcribe the second DNA strand complementary to the first DNA strand
Integration in to the host genomeIntegration in to the host genome
HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product and is an attractive target for new anti-HIV drugs
Integrase catalyzes two reactions 3-end processing in which two
deoxynucleotides are removed from the 3 ends of the viral DNA
the strand transfer reaction in which the processed 3 ends of the viral DNA are covalently ligated to the host chromosomal DNA
Integrase is a key step in allowing viral DNA to become a permanent member of the host genome
Production of Viral RNA transcriptsProduction of Viral RNA transcripts
Before HIVs provirus genes can be expressed RNA copies that can be read by host cells protein-making machinery must be producedProviral DNA produces new strands of RNA some behave like mRNA to produce proteins essential for HIV production others become encased with viral core proteins to become new viruses
HIV genes
All retroviruses contain RNA sequences that code for same three genes Flanking these genes is a sequence of similar nucleotides (LTRs)The LTR functions as a promoter5ndashLTR-- GAG POL ENV ndashLTR--3
There are 9 HIV genes encoding proteinsStructural proteins GAG POL and ENVRegulatory proteins Tat and RevAccessory proteins Nef Vif Vpu Vpr
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
HI V genome replication
Reverse transcriptase (RT)
Reverse Transcriptase Heterodimer consisting of a full 66kDa RT monomer with RNaseH domain and a 51kDa RT monomer from which the RNaseH domain has been cleaved
HIV RT is a RNA-dependant DNA polymerase transcribing ssDNA from RNA template
It has a subunit with RNaseH activity- hydrolysing the retroviral RNA from the RNA-DNA complex
Also acts as a DNA-dependant polymerase to transcribe the second DNA strand complementary to the first DNA strand
Integration in to the host genomeIntegration in to the host genome
HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product and is an attractive target for new anti-HIV drugs
Integrase catalyzes two reactions 3-end processing in which two
deoxynucleotides are removed from the 3 ends of the viral DNA
the strand transfer reaction in which the processed 3 ends of the viral DNA are covalently ligated to the host chromosomal DNA
Integrase is a key step in allowing viral DNA to become a permanent member of the host genome
Production of Viral RNA transcriptsProduction of Viral RNA transcripts
Before HIVs provirus genes can be expressed RNA copies that can be read by host cells protein-making machinery must be producedProviral DNA produces new strands of RNA some behave like mRNA to produce proteins essential for HIV production others become encased with viral core proteins to become new viruses
HIV genes
All retroviruses contain RNA sequences that code for same three genes Flanking these genes is a sequence of similar nucleotides (LTRs)The LTR functions as a promoter5ndashLTR-- GAG POL ENV ndashLTR--3
There are 9 HIV genes encoding proteinsStructural proteins GAG POL and ENVRegulatory proteins Tat and RevAccessory proteins Nef Vif Vpu Vpr
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
Reverse transcriptase (RT)
Reverse Transcriptase Heterodimer consisting of a full 66kDa RT monomer with RNaseH domain and a 51kDa RT monomer from which the RNaseH domain has been cleaved
HIV RT is a RNA-dependant DNA polymerase transcribing ssDNA from RNA template
It has a subunit with RNaseH activity- hydrolysing the retroviral RNA from the RNA-DNA complex
Also acts as a DNA-dependant polymerase to transcribe the second DNA strand complementary to the first DNA strand
Integration in to the host genomeIntegration in to the host genome
HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product and is an attractive target for new anti-HIV drugs
Integrase catalyzes two reactions 3-end processing in which two
deoxynucleotides are removed from the 3 ends of the viral DNA
the strand transfer reaction in which the processed 3 ends of the viral DNA are covalently ligated to the host chromosomal DNA
Integrase is a key step in allowing viral DNA to become a permanent member of the host genome
Production of Viral RNA transcriptsProduction of Viral RNA transcripts
Before HIVs provirus genes can be expressed RNA copies that can be read by host cells protein-making machinery must be producedProviral DNA produces new strands of RNA some behave like mRNA to produce proteins essential for HIV production others become encased with viral core proteins to become new viruses
HIV genes
All retroviruses contain RNA sequences that code for same three genes Flanking these genes is a sequence of similar nucleotides (LTRs)The LTR functions as a promoter5ndashLTR-- GAG POL ENV ndashLTR--3
There are 9 HIV genes encoding proteinsStructural proteins GAG POL and ENVRegulatory proteins Tat and RevAccessory proteins Nef Vif Vpu Vpr
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
Integration in to the host genomeIntegration in to the host genome
HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product and is an attractive target for new anti-HIV drugs
Integrase catalyzes two reactions 3-end processing in which two
deoxynucleotides are removed from the 3 ends of the viral DNA
the strand transfer reaction in which the processed 3 ends of the viral DNA are covalently ligated to the host chromosomal DNA
Integrase is a key step in allowing viral DNA to become a permanent member of the host genome
Production of Viral RNA transcriptsProduction of Viral RNA transcripts
Before HIVs provirus genes can be expressed RNA copies that can be read by host cells protein-making machinery must be producedProviral DNA produces new strands of RNA some behave like mRNA to produce proteins essential for HIV production others become encased with viral core proteins to become new viruses
HIV genes
All retroviruses contain RNA sequences that code for same three genes Flanking these genes is a sequence of similar nucleotides (LTRs)The LTR functions as a promoter5ndashLTR-- GAG POL ENV ndashLTR--3
There are 9 HIV genes encoding proteinsStructural proteins GAG POL and ENVRegulatory proteins Tat and RevAccessory proteins Nef Vif Vpu Vpr
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
Production of Viral RNA transcriptsProduction of Viral RNA transcripts
Before HIVs provirus genes can be expressed RNA copies that can be read by host cells protein-making machinery must be producedProviral DNA produces new strands of RNA some behave like mRNA to produce proteins essential for HIV production others become encased with viral core proteins to become new viruses
HIV genes
All retroviruses contain RNA sequences that code for same three genes Flanking these genes is a sequence of similar nucleotides (LTRs)The LTR functions as a promoter5ndashLTR-- GAG POL ENV ndashLTR--3
There are 9 HIV genes encoding proteinsStructural proteins GAG POL and ENVRegulatory proteins Tat and RevAccessory proteins Nef Vif Vpu Vpr
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
HIV genes
All retroviruses contain RNA sequences that code for same three genes Flanking these genes is a sequence of similar nucleotides (LTRs)The LTR functions as a promoter5ndashLTR-- GAG POL ENV ndashLTR--3
There are 9 HIV genes encoding proteinsStructural proteins GAG POL and ENVRegulatory proteins Tat and RevAccessory proteins Nef Vif Vpu Vpr
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
Proteins produced from HIV and their respective genes
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
Structural Genes
GAG- group specific antigens make up viral nucleocapsid- cylindrical core proteins (p24 a nucleoid shell protein with mol wt 24000) and several internal proteinsWhen GAG is non-functional HIV loses ability to bud out of cell
POL codes for the following HIV enzymes P10 protease reverse transcriptase endonuclease integrase
ENV codes for two major HIV surface proteins- gp120 located on external spikes of HIV and gp 41 transmembrane protein that attaches gp120 to surface of HIV
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
Regulatory Genes
TAT A transactivator protein that exerts its effect on
viral replication Tat protein interacts with a short nucleotide
sequence called TAR located within the 5LTR region of HIV mRNA transcripts
Once Tat protein binds to TAR sequence transcription of provirus by cellular RNA polymerase II accelerates 1000 times in absence of Tat viral transcription usually terminates prematurely
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
REV
Regulator of Expression of Viral proteins Selectively increases synthesis of HIV structural
proteins in latter stages of HIV disease thereby maximising production of new virus
Functions by transporting spliced amp unspliced RNAs from nucleus to cytoplasm
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
Accesory Genes
Nef N-myristylated and anchored to inner surface of plasma membrane probably in a complex with a cellular serine kinase
Makes cell more capable of producing HIV progeny
Decreasing cell surface expression of CD4 (prevent host cell re-infection with HIV)
Decreases cell surface expression of MHC in infected lymphocytes and this reduces the cytotoxic T cells response to HIV
Increases transcriptional activator Nf-kb thereby augmenting viral expression
SummarySummary
SummarySummary
