The host response to smallpox: Analysis of the gene expression program in peripheral blood cells in a nonhuman primate model

Kathleen H. Rubins, Lisa E. Hensley, Peter B. Jahrling, Adeline R. Whitney, Thomas Geisbert, John W. Huggins, Art Owen, James LeDuc, Patrick O. Brown, David A. Relman

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Smallpox has played an unparalleled role in human history and remains a significant potential threat to public health. Despite the historical significance of this disease, we know little about the underlying pathophysiology or the virulence mechanisms of the causative agent, variola virus. To improve our understanding of variola pathogenesis and variola-host interactions, we examined the molecular and cellular features of hemorrhagic smallpox in cynomolgus macaques. We used cDNA microarrays to analyze host gene expression patterns in sequential blood samples from each of 22 infected animals. Variola infection elicited striking and temporally coordinated patterns of gene expression in peripheral blood. Of particular interest were features that appear to represent an IFN response, cell proliferation, immunoglobulin gene expression, viral dose-dependent gene expression patterns, and viral modulation of the host immune response. The virtual absence of a tumor necrosis factor α/NF-κB-activated transcriptional program in the face of an overwhelming systemic infection suggests that variola gene products may ablate this response. These results provide a detailed picture of the host transcriptional response during smallpox infection, and may help guide the development of diagnostic, therapeutic, and prophylactic strategies.

Original languageEnglish (US)
Pages (from-to)15190-15195
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number42
DOIs
StatePublished - Oct 19 2004
Externally publishedYes

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Smallpox
Primates
Blood Cells
Gene Expression
Infection
Variola virus
Immunoglobulin Genes
Macaca
Cerebral Palsy
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Virulence
Public Health
Tumor Necrosis Factor-alpha
History
Cell Proliferation
Genes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The host response to smallpox : Analysis of the gene expression program in peripheral blood cells in a nonhuman primate model. / Rubins, Kathleen H.; Hensley, Lisa E.; Jahrling, Peter B.; Whitney, Adeline R.; Geisbert, Thomas; Huggins, John W.; Owen, Art; LeDuc, James; Brown, Patrick O.; Relman, David A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 42, 19.10.2004, p. 15190-15195.

Research output: Contribution to journalArticle

Rubins, Kathleen H. ; Hensley, Lisa E. ; Jahrling, Peter B. ; Whitney, Adeline R. ; Geisbert, Thomas ; Huggins, John W. ; Owen, Art ; LeDuc, James ; Brown, Patrick O. ; Relman, David A. / The host response to smallpox : Analysis of the gene expression program in peripheral blood cells in a nonhuman primate model. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 42. pp. 15190-15195.
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