Technical knockout: understanding poxvirus pathogenesis by selectively deleting viral immunomodulatory genes

Cellular Microbiology
J B Johnston, G McFadden

Abstract

The study of viral pathogens with genomes as large and complex as poxviruses represents a constant experimental challenge. Advances in recombinant DNA technologies have provided sophisticated methods to produce mutants defective in one or more viral genes, termed knockout (KO) viruses, thereby facilitating research into the impact of specific gene products on viral pathogenesis. Such strategies have rapidly advanced the systematic mining of many poxvirus genomes and enabled researchers to identify and characterize poxvirus genes whose functions represent the culmination of host and pathogen coevolution. Of particular interest are the multiple classes of virus-encoded immunomodulatory proteins that have evolved specifically to allow poxviruses to evade, obstruct or subvert critical elements within the host innate and acquired immune responses. Functional characterization of these viral genes by generating KO viruses and investigating the phenotypic changes that result is an important tool for understanding the molecular mechanisms underlying poxvirus replication and pathogenesis. Moreover, the insights gained have led to new developments in basic and clinical virology, provided a basis for the design of new vaccines and antivira...Continue Reading

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Citations

Jan 18, 2007·Immunology and Cell Biology·Marianne M StanfordGeeta Chaudhri
Oct 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Grant McFadden
Aug 31, 2007·Journal of Virology·Marianne M StanfordGrant McFadden
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