© Elsevier, 2011.Principles of Molecular Virology Virus Infection Major responses of plants and animals to virus infections The scientific basis for prevention

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


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


Movement ProteinsMovement Proteins


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


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


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


Immune Responses to Virus Immune Responses to Virus Infections in AnimalsInfections in Animals

Humoral immune response


Cell-mediated immunityCell-mediated immunity


Recognition of virus-infected cellsRecognition of virus-infected cells


Viruses and ApoptosisViruses and Apoptosis


InterferonsInterferons

1957, Alick Issacs and Jean Lindenmann


Different types of interferon (IFN)Different types of interferon (IFN)

• IFN-α

• IFN-β

• Other interferons


Induction of interferon synthesisInduction of interferon synthesis

• Virus infection

• Double-stranded (ds) RNA

• Metabolic inhibitors


Interferon Antiviral MechanismsInterferon Antiviral Mechanisms

Induction of 2',5'-oligo A synthetase


Interferon Antiviral MechanismsInterferon Antiviral Mechanisms

Activation of PKR


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


Virus–Host InteractionsVirus–Host Interactions

Site of virus entry

into the body


Transmission of viruses through Transmission of viruses through the environmentthe environment


Local infectionLocal infection

Virus infection of polarized epithelial cells


Outcome of infectionOutcome of infection

• Clearance vs. persistence• Antigenic variation• Antigenic drift• Antigenic shift


The Course of Virus InfectionsThe Course of Virus Infections

• Abortive Infection• Acute Infection• Chronic Infection• Persistent Infection• Latent Infection


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


RNA interference (RNAi)RNA interference (RNAi)


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


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


Chemotherapy of Virus InfectionsChemotherapy of Virus Infections

• Attachment

• Penetration/uncoating - Amantadine

• Genome replication -

Acyclovir, reverse transcriptase inhibitors

• Gene expression, release - ?

• Maturation - protease inhibitors


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.


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

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© Elsevier, 2011.Principles of Molecular Virology Virus Infection Major responses of plants and animals to virus infections The scientific basis for prevention