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Virus Infection. Major responses of plants and animals to virus infections The scientific basis for prevention and treatment of virus diseases. Transmission of plant viruses. Mechanical Seeds Vegetative propagation/grafting Vectors - PowerPoint PPT Presentation
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Principles of Molecular Virology © Elsevier, 2011.
Virus InfectionVirus Infection
• Major responses of plants and animals to virus
infections
• The scientific basis for prevention and treatment of
virus diseases
Principles of Molecular Virology © Elsevier, 2011.
Transmission of plant virusesTransmission of plant viruses
• Mechanical• Seeds• Vegetative propagation/grafting• Vectors• Bacteria (e.g. Agrobacterium tumefaciens - Ti plasmid)• Fungi• Nematodes• Arthropods:
– insects– arachnids
Principles of Molecular Virology © Elsevier, 2011.
Movement ProteinsMovement Proteins
Principles of Molecular Virology © Elsevier, 2011.
Symptoms of virus infection in Symptoms of virus infection in plantsplants
• Growth retardation• Distortion• Mosaic patterning on leaves• Yellowing• Wilting
Resulting from:– Necrosis– Hypoplasia– Hyperplasia
Principles of Molecular Virology © Elsevier, 2011.
The hypersensitive responseThe hypersensitive response
• Pathogenesis-related (PR) proteins
• Production of cell wall phenolic substances
• Release of active oxygen species
• Production of phytoalexins
• Accumulation of salicylic acid
Principles of Molecular Virology © Elsevier, 2011.
Virus-resistant plantsVirus-resistant plants
• Traditional plant breeding• Transgenic plants expressing:
– Virus coat proteins– Intact or partial virus replicases– Antisense RNAs– Defective virus genomes– Satellite sequences– Catalytic RNA sequences (ribozymes)– Modified movement proteins
Principles of Molecular Virology © Elsevier, 2011.
Immune Responses to Virus Immune Responses to Virus Infections in AnimalsInfections in Animals
Humoral immune response
Principles of Molecular Virology © Elsevier, 2011.
Cell-mediated immunityCell-mediated immunity
Principles of Molecular Virology © Elsevier, 2011.
Recognition of virus-infected cellsRecognition of virus-infected cells
Principles of Molecular Virology © Elsevier, 2011.
Viruses and ApoptosisViruses and Apoptosis
Principles of Molecular Virology © Elsevier, 2011.
InterferonsInterferons
1957, Alick Issacs and Jean Lindenmann
Principles of Molecular Virology © Elsevier, 2011.
Different types of interferon (IFN)Different types of interferon (IFN)
• IFN-α
• IFN-β
• Other interferons
Principles of Molecular Virology © Elsevier, 2011.
Induction of interferon synthesisInduction of interferon synthesis
• Virus infection
• Double-stranded (ds) RNA
• Metabolic inhibitors
Principles of Molecular Virology © Elsevier, 2011.
Interferon Antiviral MechanismsInterferon Antiviral Mechanisms
Induction of 2',5'-oligo A synthetase
Principles of Molecular Virology © Elsevier, 2011.
Interferon Antiviral MechanismsInterferon Antiviral Mechanisms
Activation of PKR
Principles of Molecular Virology © Elsevier, 2011.
Evasion of Immune Responses by Evasion of Immune Responses by VirusesViruses
• Inhibition of MHC-I-restricted antigen presentation
• Inhibition of MHC-II-restricted antigen presentation
• Inhibition of natural killer cell lysis
• Interference with apoptosis
• Inhibition of cytokine action
• Evasion of humoral immunity
• Evasion of the complement cascade
Principles of Molecular Virology © Elsevier, 2011.
Virus–Host InteractionsVirus–Host Interactions
Site of virus entry
into the body
Principles of Molecular Virology © Elsevier, 2011.
Transmission of viruses through Transmission of viruses through the environmentthe environment
Principles of Molecular Virology © Elsevier, 2011.
Local infectionLocal infection
Virus infection of polarized epithelial cells
Principles of Molecular Virology © Elsevier, 2011.
Outcome of infectionOutcome of infection
• Clearance vs. persistence• Antigenic variation• Antigenic drift• Antigenic shift
Principles of Molecular Virology © Elsevier, 2011.
The Course of Virus InfectionsThe Course of Virus Infections
• Abortive Infection• Acute Infection• Chronic Infection• Persistent Infection• Latent Infection
Principles of Molecular Virology © Elsevier, 2011.
Prevention and Therapy of Virus Prevention and Therapy of Virus InfectionInfection
• Drugs (cure) versus vaccines (prevention)
– Synthetic vaccines
– Recombinant vaccines
– DNA vaccines
– Subunit vaccines
– Virus vectors are recombinant viruses
– Inactivated vaccines
– Attenuated vaccines
Principles of Molecular Virology © Elsevier, 2011.
RNA interference (RNAi)RNA interference (RNAi)
Principles of Molecular Virology © Elsevier, 2011.
Virus Vectors and Gene TherapyVirus Vectors and Gene Therapy
• Delivery of large biomolecules to cells
• The possibility of targeting a specific cell type
• High potency of action due to replication of vector
• Potential to treat cancer
Principles of Molecular Virology © Elsevier, 2011.
Chemotherapy of Virus InfectionsChemotherapy of Virus Infections
Chemotherapeutic index:
Dose of drug that inhibits virus replication
Dose of drug that is toxic to host
• The process targeted by a drug must be essential for
replication• The drug is active against the virus but has
‘acceptable toxicity’ to the host
Principles of Molecular Virology © Elsevier, 2011.
Chemotherapy of Virus InfectionsChemotherapy of Virus Infections
• Attachment
• Penetration/uncoating - Amantadine
• Genome replication -
Acyclovir, reverse transcriptase inhibitors
• Gene expression, release - ?
• Maturation - protease inhibitors
Principles of Molecular Virology © Elsevier, 2011.
SummarySummary
Virus infection is a complex, multistage interaction between the virus and the host organism.
The course and outcome of any infection are the result of a balance between host and virus.
Host factors include route of virus transmission and the immune response.
Virus processes include site of initial infection, spread throughout the host, regulation of gene expression to evade the immune response.
Principles of Molecular Virology © Elsevier, 2011.
Further ReadingFurther Reading
Aliyari, R. & Ding S.W. (2009) RNA-based viral immunity initiated by the Dicer family of host immune receptors. Immunol Rev. 227(1): 176-188Crotty, S. and Andino, R. (2002) Implications of high RNA virus mutation rates: lethal mutagenesis and the antiviral drug ribavirin. Microbes and Infection, 4: 1301–1307Coiras, M., López-Huertas, M.R., Pérez-Olmeda, M. and Alcamí, J. (2009) Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs. Nat Rev Microbiol. 7(11): 798-812Cullen, B.R. (2010) Five Questions about Viruses and MicroRNAs. PLoS Pathog 6(2): e1000787Ding, S.W. & Voinnet. O. (2007) Antiviral immunity directed by small RNAs. Cell 130(3): 413-426Kindt, T.J., Goldsby, R.A., Osborne, B.A. & Kuby, J. (2007) Kuby Immunology. W.H. Freeman, ISBN1429202114.Kutzler, M.A. & Weiner, D.B. (2008) DNA vaccines: ready for prime time? Nature Reviews Genetics 9: 776-788Lisnića, V.J., Krmpotića, A. and Jonjića, S. (2010) Modulation of natural killer cell activity by viruses. Current Opinion in Microbiology 13(4): 530-539Liu, T.C. & Kirn, D. (2008) Gene therapy progress and prospects cancer: oncolytic viruses. Gene Ther 15(12): 877-884Lu, L.F. & Liston A. (2009) MicroRNA in the immune system, microRNA as an immune system. Immunology 127(3): 291-298Mallery, D.L. et al (2010) Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21) PNAS USA 107(46): 19985-19990Palese P. (2006) Making better influenza virus vaccines? Emerg Infect Dis. http://www.cdc.gov/ncidod/EID/vol12no01/05-1043.htmRandall, R.E. and Goodbourn, S. (2008) Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol. 89(1)Sen, G.C. (2001) Viruses and interferons. Annual Review of Microbiology, 55: 255–281Tortorella, D. et al. (2000) Viral subversion of the immune system. Annual Review of Immunology, 18: 861–926Welsh, R.M. et al. (2004) Immunological memory to viral infections. Annual Review of Immunology, 22: 711–743