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Poxviruses and immune evasion
Bruce T Seet1, J B Johnston, Craig R Brunetti
1Department of Microbiology and Immunology, University of Western Ontario, London, Canada. btseet@mshri.ca
Abstract:
Large DNA viruses defend against hostile assault executed by the host immune system by producing an array of gene products that systematically sabotage key components of the inflammatory response. Poxviruses target many of the primary mediators of innate immunity including interferons, tumor necrosis factors, interleukins, complement, and chemokines. Poxviruses also manipulate a variety of intracellular signal transduction pathways such as the apoptotic response. Many of the poxvirus genes that disrupt these pathways have been hijacked directly from the host immune system, while others have demonstrated no clear resemblance to any known host genes. Nonetheless, the immunological targets and the diversity of strategies used by poxviruses to disrupt these host pathways have provided important insights into diverse aspects of immunology, virology, and inflammation. Furthermore, because of their anti-inflammatory nature, many of these poxvirus proteins hold promise as potential therapeutic agents for acute or chronic inflammatory conditions.
Insights
Large DNA viruses like poxviruses produce proteins to evade the host immune system, targeting inflammation and immunity. These viral proteins offer potential anti-inflammatory therapies for various conditions.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Large DNA viruses, particularly poxviruses, possess sophisticated mechanisms to counteract host immune defenses.
- These viruses produce gene products that interfere with critical components of the inflammatory and innate immune responses.
Purpose of the Study:
- To elucidate the strategies employed by poxviruses to subvert host immunity and inflammation.
- To explore the potential therapeutic applications of poxviral anti-inflammatory proteins.
Main Methods:
- Analysis of poxvirus genomes and gene products targeting host immune pathways.
- Investigation of viral manipulation of intracellular signaling, including apoptosis.
- Comparison of viral immune evasion genes with host counterparts.
Main Results:
- Poxviruses target key immune mediators such as interferons, tumor necrosis factors, interleukins, complement, and chemokines.
- Viral proteins disrupt intracellular signaling pathways, including apoptotic responses.
- Some viral immune evasion genes are derived from the host, while others are novel.
Conclusions:
- Poxviruses utilize diverse strategies, including gene acquisition from the host, to disable innate immunity and inflammation.
- Understanding these viral mechanisms provides crucial insights into immunology, virology, and inflammatory processes.
- Poxviral proteins exhibiting anti-inflammatory properties represent promising candidates for therapeutic development.