A limited number of Simian Immunodeficiency Virus (SIV) env variants are transmitted to rhesus macaques vaginally inoculated with SIVmac251

Mars Stone, Brandon F. Keele, Zhong Min Ma, Elizabeth Bailes, Joseph Dutra, Beatrice H. Hahn, George M. Shaw, Chris J Miller

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Single-genome amplification (SGA) and sequencing of HIV-1 RNA in plasma of acutely infected humans allows the identification and enumeration of transmitted/founder viruses responsible for productive systemic infection. Use of this strategy as a means for identifying transmitted viruses suggested that intrarectal simian immunodeficiency virus (SIV) inoculation of macaques recapitulates key features of human rectal infection. However, no studies have used the SGA strategy to identify vaginally transmitted virus(es) in macaques or to determine how early SIV diversification in vaginally infected animals compares with HIV-1 in humans. We used SGA to amplify 227 partial env sequences from a SIVmac251 challenge stock and from seven rhesus macaques at the earliest plasma viral RNA-positive time point after low- and high-dose intravaginal inoculation. Sequences were analyzed phylogenetically to determine the relationship of transmitted/founder viruses within and between each animal and the challenge stock. In each animal, discrete low-diversity env sequence lineages were evident, and these coalesced phylogenetically to identical or near-identical env sequences in the challenge stock, thus confirming the validity of the SGA sequencing and modeling strategy for identifying vaginally transmitted SIV. Between 1 and 10 viruses were responsible for systemic infection, similar to humans infected by sexual contact, and the set of viruses transmitted to the seven animals studied represented the full genetic constellation of the challenge stock. These findings recapitulate many of the features of sexual HIV-1 transmission in women. Furthermore, the SIV rhesus macaque model can be used to understand the factors that influence the transmission of single versus multiple SIV variants.

Original languageEnglish (US)
Pages (from-to)7083-7095
Number of pages13
JournalJournal of Virology
Volume84
Issue number14
DOIs
StatePublished - Jul 2010

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
Macaca mulatta
Viruses
viruses
Human immunodeficiency virus 1
Genome
HIV-1
genome
Macaca
animals
Infection
infection
RNA
Forensic Anthropology
Viral RNA
dosage

ASJC Scopus subject areas

  • Immunology
  • Virology

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A limited number of Simian Immunodeficiency Virus (SIV) env variants are transmitted to rhesus macaques vaginally inoculated with SIVmac251. / Stone, Mars; Keele, Brandon F.; Ma, Zhong Min; Bailes, Elizabeth; Dutra, Joseph; Hahn, Beatrice H.; Shaw, George M.; Miller, Chris J.

In: Journal of Virology, Vol. 84, No. 14, 07.2010, p. 7083-7095.

Research output: Contribution to journalArticle

Stone, Mars ; Keele, Brandon F. ; Ma, Zhong Min ; Bailes, Elizabeth ; Dutra, Joseph ; Hahn, Beatrice H. ; Shaw, George M. ; Miller, Chris J. / A limited number of Simian Immunodeficiency Virus (SIV) env variants are transmitted to rhesus macaques vaginally inoculated with SIVmac251. In: Journal of Virology. 2010 ; Vol. 84, No. 14. pp. 7083-7095.
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