Roles of substrate availability and infection of resting and activated CD4+ T cells in transmission and acute simian immunodeficiency virus infection

Zhi Qiang Zhang, Stephen W. Wietgrefe, Qingsheng Li, Marta Dykhuizen Shore, Lijie Duan, Cavan Reilly, Jeffrey D. Lifson, Ashley T. Haase

Research output: Contribution to journalArticle

167 Citations (Scopus)

Abstract

In studies of sexual mucosal transmission and early stages of simian immunodeficiency virus (SIV) and HIV infections, productive infection predominates in CD4+ T cell populations, in both ostensibly resting and activated cells. The surprising ability of SIV and HIV to replicate in resting cells in vivo, in contrast to propagation of infection in vitro, suggested a model in which during the early stages of infection these viruses exploit the greater availability of resting cells to maintain unbroken chains of transmission from an infected resting cell to another resting cell nearby. Because immune activation in response to infection provides more activated CD4+ T cells, these viruses take advantage of the greater efficiency of virus production and spread in activated cells for propagation and dissemination of infection. In this article, we report the results of experimental tests of this model, including visualization at the light microscopic level and direct analysis of virus production by cells in tissues. Analysis of tissues of rhesus macaques inoculated intravaginally or i.v. with SIV supports the proposed roles of target cell availability, susceptibility, and virus production by infected resting and activated CD4+ T cells in mucosal transmission and early infection, and points to a potential role for topical antiinflammatory agents in moderating the initial propagation of infection.

Original languageEnglish (US)
Pages (from-to)5640-5645
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number15
DOIs
StatePublished - Apr 13 2004

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Simian Immunodeficiency Virus
Virus Diseases
T-Lymphocytes
Infection
Viruses
Infectious Disease Transmission
Macaca mulatta
HIV Infections
Anti-Inflammatory Agents
Theoretical Models
HIV
Light

ASJC Scopus subject areas

  • General

Cite this

Roles of substrate availability and infection of resting and activated CD4+ T cells in transmission and acute simian immunodeficiency virus infection. / Zhang, Zhi Qiang; Wietgrefe, Stephen W.; Li, Qingsheng; Shore, Marta Dykhuizen; Duan, Lijie; Reilly, Cavan; Lifson, Jeffrey D.; Haase, Ashley T.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 15, 13.04.2004, p. 5640-5645.

Research output: Contribution to journalArticle

Zhang, Zhi Qiang ; Wietgrefe, Stephen W. ; Li, Qingsheng ; Shore, Marta Dykhuizen ; Duan, Lijie ; Reilly, Cavan ; Lifson, Jeffrey D. ; Haase, Ashley T. / Roles of substrate availability and infection of resting and activated CD4+ T cells in transmission and acute simian immunodeficiency virus infection. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 15. pp. 5640-5645.
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