Low dose rectal inoculation of rhesus macaques by SIV SME660 or SIV MAC251 recapitulates human mucosal infection by HIV-1

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Recently, we developed a novel approach to the identification of transmitted or early founder HIV -1 genomes in acutely infected humans based on single genome amplification and sequencing. Here we tested this approach in 18 acutely infected Indian rhesus macaques to determine the molecular features of SIV transmission. Animals were inoculated intrarectally (IR) or intravenously (IV) 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 one to five weeks after infection. IR inoculation was followed by productive ... continued below

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Koraber, Bette; Perelson, Alan; Hraber, Peter; Giorgi, E & Bhattacharya, T January 1, 2009.

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Recently, we developed a novel approach to the identification of transmitted or early founder HIV -1 genomes in acutely infected humans based on single genome amplification and sequencing. Here we tested this approach in 18 acutely infected Indian rhesus macaques to determine the molecular features of SIV transmission. Animals were inoculated intrarectally (IR) or intravenously (IV) 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 one to five weeks after infection. IR inoculation was followed by productive infection by one or few viruses (median 1; range 1-5) that diversified randomly with near star-like 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 few nuc1eotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder virus( es). IV infection was approximately 10,000-fold more efficient than IR 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.

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  • Journal Name: Journal of Experimental Medicine

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  • Report No.: LA-UR-09-00061
  • Report No.: LA-UR-09-61
  • Grant Number: AC52-06NA25396
  • Office of Scientific & Technical Information Report Number: 956474
  • Archival Resource Key: ark:/67531/metadc927588

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  • January 1, 2009

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  • Nov. 13, 2016, 7:26 p.m.

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  • Dec. 12, 2016, 12:21 p.m.

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Koraber, Bette; Perelson, Alan; Hraber, Peter; Giorgi, E & Bhattacharya, T. Low dose rectal inoculation of rhesus macaques by SIV SME660 or SIV MAC251 recapitulates human mucosal infection by HIV-1, article, January 1, 2009; [New Mexico]. (digital.library.unt.edu/ark:/67531/metadc927588/: accessed September 25, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.