Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus

Christopher J. Miller, Qingsheng Li, Kristina Abel, Eun Young Kim, Zhong Min Ma, Stephen Wietgrefe, Lisa La Franco-Scheuch, Lara Compton, Lijie Duan, Marta Dykhuizen Shore, Mary Zupancic, Marc Busch, John Carlis, Steven Wolinksy, Ashley T. Haase

Research output: Contribution to journalArticle

337 Scopus citations

Abstract

In the current global AIDS pandemic, more than half of new human immunodeficiency virus type 1 (HFV-I) infections are acquired by women through intravaginal HIV exposure. For this study, we explored pathogenesis issues relevant to the development of effective vaccines to prevent infection by this route, using an animal model in which female rhesus macaques were exposed intravaginally to a high dose of simian immunodeficiency virus (STV). We examined in detail the events that transpire from hours to a few days after intravaginal SIV exposure through week 4 to provide a framework for understanding the propagation, dissemination, and establishment of infection in lymphatic tissues (LTs) during the acute stage of infection. We show that the mucosal barrier greatly limits the infection of cervicovaginal tissues, and thus the initial founder populations of infected cells are small. While there was evidence of rapid dissemination to distal sites, we also show that continuous seeding from an expanding source of production at the portal of entry is likely critical for the later establishment of a productive infection throughout the systemic LTs. The initially small founder populations and dependence on continuous seeding to establish a productive infection in systemic LTs define a small window of maximum vulnerability for the virus in which there is an opportunity for the host, vaccines, or other interventions to prevent or control infection.

Original languageEnglish (US)
Pages (from-to)9217-9227
Number of pages11
JournalJournal of virology
Volume79
Issue number14
DOIs
StatePublished - Jul 2005

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Miller, C. J., Li, Q., Abel, K., Kim, E. Y., Ma, Z. M., Wietgrefe, S., La Franco-Scheuch, L., Compton, L., Duan, L., Shore, M. D., Zupancic, M., Busch, M., Carlis, J., Wolinksy, S., & Haase, A. T. (2005). Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. Journal of virology, 79(14), 9217-9227. https://doi.org/10.1128/JVI.79.14.9217-9227.2005