Genome-wide analysis of the host response to variola infection

Overview

Rubins, K.¹, Whitney, A.¹, Jahrling, P.², Hensley, L.², Huggins, J.² LeDuc, J.³, Brown, P.¹, Relman, D.¹

¹ Stanford University, CA, USA ² United States Army Research Institute of Infectious Diseases, Frederick, MD, USA³ CDC, Atlanta, USA

Variola and related poxvirus possess a variety of potential mechanisms for interfering with host innate immune defense mechanisms. In order to improve our understanding of variola pathogenesis and variola-host interactions we have examined the molecular features of smallpox infection in vivo. Using high-density cDNA microarrays we have analyzed genome-wide host expression patterns in sequential blood samples from lethally infected cynomolgus macaques in an animal model of smallpox.

Three separate studies of macaque variola infection provided data involving different routes of infection and different doses. These data revealed dramatic, highly choreographed patterns of gene expression response to variola infection. Of particular interest were features of the data that may reflect viral modulation of the host immune response, immunoglobulin gene expression, the interferon response, TNFα /NFκ B pathways, and a cell proliferatio/cell cycle response.

Further analysis and additional experiments may elucidate correlates and mechanisms of host defense subversion, viral tropism, and suggest new dignostic, prognostic, therapeutic and prophylactic approaches.

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