title: Comparison of host cell gene expression in cowpox, monkeypox or vaccinia virus-infected cells reveals virus-specific regulation of immune response genes.
abstract: BACKGROUND
  Animal-borne orthopoxviruses, like monkeypox, vaccinia and the closely related cowpox virus, are all capable of causing zoonotic infections in humans, representing a potential threat to human health. The disease caused by each virus differs in terms of symptoms and severity, but little is yet know about the reasons for these varying phenotypes. They may be explained by the unique repertoire of immune and host cell modulating factors encoded by each virus. In this study, we analysed the specific modulation of the host cell's gene expression profile by cowpox, monkeypox and vaccinia virus infection. We aimed to identify mechanisms that are either common to orthopoxvirus infection or specific to certain orthopoxvirus species, allowing a more detailed description of differences in virus-host cell interactions between individual orthopoxviruses. To this end, we analysed changes in host cell gene expression of HeLa cells in response to infection with cowpox, monkeypox and vaccinia virus, using whole-genome gene expression microarrays, and compared these to each other and to non-infected cells.
  
  
  RESULTS
  Despite a dominating non-responsiveness of cellular transcription towards orthopoxvirus infection, we could identify several clusters of infection-modulated genes. These clusters are either commonly regulated by orthopoxvirus infection or are uniquely regulated by infection with a specific orthopoxvirus, with major differences being observed in immune response genes. Most noticeable was an induction of genes involved in leukocyte migration and activation in cowpox and monkeypox virus-infected cells, which was not observed following vaccinia virus infection.
  
  
  CONCLUSIONS
  Despite their close genetic relationship, the expression profiles induced by infection with different orthopoxviruses vary significantly. It may be speculated that these differences at the cellular level contribute to the individual characteristics of cowpox, monkeypox and vaccinia virus infections in certain host species.
authors: Centre for Biological Threats and Special Pathogens 1, Robert Koch Institute, Nordufer 20, Berlin, Germany. nitschea@rki.de
authors: Daniel
authors: D
authors: Bourquain
authors: Piotr Wojtek
authors: PW
authors: Dabrowski
authors: Andreas
authors: A
authors: Nitsche
mesh_terms: D015608:Cowpox virus / Q000276:immunology*; D004847:Epithelial Cells / Q000821:virology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D046228:Microarray Analysis; D008993:Monkeypox virus / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*