Virus 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 viruses
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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 Proteins
Principles of Molecular Virology
© Elsevier, 2011.
Symptoms of virus infection in
plants
• Growth retardation
• Distortion
• Mosaic patterning on leaves
• Yellowing
• Wilting
Resulting from:
– Necrosis
– Hypoplasia
– Hyperplasia
Principles of Molecular Virology
© Elsevier, 2011.
The 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 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
Infections in Animals
Humoral immune response
Principles of Molecular Virology
© Elsevier, 2011.
Cell-mediated immunity
Principles of Molecular Virology
© Elsevier, 2011.
Recognition of virus-infected cells
Principles of Molecular Virology
© Elsevier, 2011.
Viruses and Apoptosis
Principles of Molecular Virology
© Elsevier, 2011.
Interferons
1957, Alick Issacs and Jean Lindenmann
Principles of Molecular Virology
© Elsevier, 2011.
Different types of interferon (IFN)
• IFN-α
• IFN-β
• Other interferons
Principles of Molecular Virology
© Elsevier, 2011.
Induction of interferon synthesis
• Virus infection
• Double-stranded (ds) RNA
• Metabolic inhibitors
Principles of Molecular Virology
© Elsevier, 2011.
Interferon Antiviral Mechanisms
Induction of 2',5'-oligo A synthetase
Principles of Molecular Virology
© Elsevier, 2011.
Interferon Antiviral Mechanisms
Activation of PKR
Principles of Molecular Virology
© Elsevier, 2011.
Evasion of Immune Responses by
Viruses
• 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 Interactions
Site of virus entry
into the body
Principles of Molecular Virology
© Elsevier, 2011.
Transmission of viruses through
the environment
Principles of Molecular Virology
© Elsevier, 2011.
Local infection
Virus infection of polarized epithelial cells
Principles of Molecular Virology
© Elsevier, 2011.
Outcome of infection
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Clearance vs. persistence
Antigenic variation
Antigenic drift
Antigenic shift
Principles of Molecular Virology
© Elsevier, 2011.
The Course of Virus Infections
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Abortive Infection
Acute Infection
Chronic Infection
Persistent Infection
Latent Infection
Principles of Molecular Virology
© Elsevier, 2011.
Prevention and Therapy of Virus
Infection
• 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)
Principles of Molecular Virology
© Elsevier, 2011.
Virus 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 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 Infections
• Attachment
• Penetration/uncoating - Amantadine
• Genome replication Acyclovir, reverse transcriptase inhibitors
• Gene expression, release - ?
• Maturation - protease inhibitors
Principles of Molecular Virology
© Elsevier, 2011.
Summary
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 Reading
Aliyari, R. & Ding S.W. (2009) RNA-based viral immunity initiated by the Dicer family of host immune receptors. Immunol
Rev. 227(1): 176-188
Crotty, S. and Andino, R. (2002) Implications of high RNA virus mutation rates: lethal mutagenesis and the antiviral drug
ribavirin. Microbes and Infection, 4: 1301–1307
Coiras, 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): 798-812
Cullen, B.R. (2010) Five Questions about Viruses and MicroRNAs. PLoS Pathog 6(2): e1000787
Ding, S.W. & Voinnet. O. (2007) Antiviral immunity directed by small RNAs. Cell 130(3): 413-426
Kindt, T.J., Goldsby, R.A., Osborne, B.A. & Kuby, J. (2007) Kuby Immunology. W.H. Freeman, ISBN
1429202114.
Kutzler, M.A. & Weiner, D.B. (2008) DNA vaccines: ready for prime time? Nature Reviews Genetics 9: 776-788
Lisnića, V.J., Krmpotića, A. and Jonjića, S. (2010) Modulation of natural killer cell activity by viruses. Current Opinion in
Microbiology 13(4): 530-539
Liu, T.C. & Kirn, D. (2008) Gene therapy progress and prospects cancer: oncolytic viruses. Gene Ther 15(12): 877-884
Lu, L.F. & Liston A. (2009) MicroRNA in the immune system, microRNA as an immune system. Immunology 127(3): 291298
Mallery, D.L. et al (2010) Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21) PNAS
USA 107(46): 19985-19990
Palese P. (2006) Making better influenza virus vaccines? Emerg Infect Dis. http://www.cdc.gov/ncidod/EID/vol12no01/051043.htm
Randall, 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: 255–281
Tortorella, D. et al. (2000) Viral subversion of the immune system. Annual Review of Immunology, 18: 861–926
Welsh, R.M. et al. (2004) Immunological memory to viral infections. Annual Review of Immunology, 22: 711–743
Principles of Molecular Virology
© Elsevier, 2011.