Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1

Brandon F. Keele, Hui Li, Gerald H. Learn, Peter Hraber, Elena E. Giorgi, Truman Grayson, Chuanxi Sun, Yalu Chen, Wendy W. Yeh, Norman L. Letvin, John R. Mascola, Gary J. Nabel, Barton F. Haynes, Tanmoy Bhattacharya, Alan S. Perelson, Bette T. Korber, Beatrice H. Hahn, George M. Shaw

Research output: Contribution to journalArticle

Abstract

We recently developed a novel strategy to identify transmitted HIV-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. Here, we used this approach to determine the molecular features of simian immunodeficiency virus (SIV) transmission in 18 experimentally infected Indian rhesus macaques. Animals were inoculated intrarectally (i.r.) or intravenously (i.v.) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV-1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA 1-5 wk after infection. i.r. inoculation was followed by productive infection by one or a few viruses (median 1; range 1-5) that diversified randomly with near starlike phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or a few nucleotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder viruses. i.v. infection was >2,000-fold more efficient than i.r. infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV-1, and thus validate the SIV-macaque mucosal infection model for HIV-1 vaccine and microbicide research.

Original languageEnglish (US)
Pages (from-to)1117-1134
Number of pages18
JournalJournal of Experimental Medicine
Volume206
Issue number5
DOIs
StatePublished - May 11 2009
Externally publishedYes

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Simian Immunodeficiency Virus
Macaca mulatta
HIV-1
Viruses
Infection
Genome
Poisson Distribution
AIDS Vaccines
Architectural Accessibility
Viremia
Consensus Sequence
Macaca
Virus Diseases
Phylogeny
Anti-Infective Agents
Virion
HIV Infections
Nucleotides
RNA
Mutation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. / Keele, Brandon F.; Li, Hui; Learn, Gerald H.; Hraber, Peter; Giorgi, Elena E.; Grayson, Truman; Sun, Chuanxi; Chen, Yalu; Yeh, Wendy W.; Letvin, Norman L.; Mascola, John R.; Nabel, Gary J.; Haynes, Barton F.; Bhattacharya, Tanmoy; Perelson, Alan S.; Korber, Bette T.; Hahn, Beatrice H.; Shaw, George M.

In: Journal of Experimental Medicine, Vol. 206, No. 5, 11.05.2009, p. 1117-1134.

Research output: Contribution to journalArticle

Keele, BF, Li, H, Learn, GH, Hraber, P, Giorgi, EE, Grayson, T, Sun, C, Chen, Y, Yeh, WW, Letvin, NL, Mascola, JR, Nabel, GJ, Haynes, BF, Bhattacharya, T, Perelson, AS, Korber, BT, Hahn, BH & Shaw, GM 2009, 'Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1', Journal of Experimental Medicine, vol. 206, no. 5, pp. 1117-1134. https://doi.org/10.1084/jem.20082831
Keele, Brandon F. ; Li, Hui ; Learn, Gerald H. ; Hraber, Peter ; Giorgi, Elena E. ; Grayson, Truman ; Sun, Chuanxi ; Chen, Yalu ; Yeh, Wendy W. ; Letvin, Norman L. ; Mascola, John R. ; Nabel, Gary J. ; Haynes, Barton F. ; Bhattacharya, Tanmoy ; Perelson, Alan S. ; Korber, Bette T. ; Hahn, Beatrice H. ; Shaw, George M. / Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. In: Journal of Experimental Medicine. 2009 ; Vol. 206, No. 5. pp. 1117-1134.
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AU - Hraber, Peter

AU - Giorgi, Elena E.

AU - Grayson, Truman

AU - Sun, Chuanxi

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AU - Yeh, Wendy W.

AU - Letvin, Norman L.

AU - Mascola, John R.

AU - Nabel, Gary J.

AU - Haynes, Barton F.

AU - Bhattacharya, Tanmoy

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