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

Publication ,  Journal Article
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 ...
Published in: J Exp Med
May 11, 2009

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.

Duke Scholars

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

May 11, 2009

Volume

206

Issue

5

Start / End Page

1117 / 1134

Location

United States

Related Subject Headings

  • Viremia
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • SAIDS Vaccines
  • Mutation
  • Macaca mulatta
  • Intestinal Mucosa
  • Immunology
  • Humans
 

Citation

APA
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MLA
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Keele, B. F., Li, H., Learn, G. H., Hraber, P., Giorgi, E. E., Grayson, T., … Shaw, G. M. (2009). Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J Exp Med, 206(5), 1117–1134. https://doi.org/10.1084/jem.20082831
Keele, Brandon F., Hui Li, Gerald H. Learn, Peter Hraber, Elena E. Giorgi, Truman Grayson, Chuanxi Sun, et al. “Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1.J Exp Med 206, no. 5 (May 11, 2009): 1117–34. https://doi.org/10.1084/jem.20082831.
Keele BF, Li H, Learn GH, Hraber P, Giorgi EE, Grayson T, et al. Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J Exp Med. 2009 May 11;206(5):1117–34.
Keele, Brandon F., et al. “Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1.J Exp Med, vol. 206, no. 5, May 2009, pp. 1117–34. Pubmed, doi:10.1084/jem.20082831.
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. Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J Exp Med. 2009 May 11;206(5):1117–1134.

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

May 11, 2009

Volume

206

Issue

5

Start / End Page

1117 / 1134

Location

United States

Related Subject Headings

  • Viremia
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • SAIDS Vaccines
  • Mutation
  • Macaca mulatta
  • Intestinal Mucosa
  • Immunology
  • Humans