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

Journal Article · Thu Jan 01 04:00:00 EST 2009 · Journal of Experimental Medicine

OSTI ID:956474

Koraber, Bette ^[1]; Perelson, Alan ^[1]; Hraber, Peter ^[1]; Giorgi, E ^[1]; Bhattacharya, T ^[1]

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1. Los Alamos National Laboratory

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.

• Research Organization: Los Alamos National Laboratory (LANL)
• Sponsoring Organization: DOE
• DOE Contract Number: AC52-06NA25396
• OSTI ID: 956474
• Report Number(s): LA-UR-09-00061; LA-UR-09-61
• Journal Information: Journal of Experimental Medicine, Journal Name: Journal of Experimental Medicine; ISSN 0022-1007; ISSN JEMEAV
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AIDS VIRUS
AMPLIFICATION
ANIMALS
DISTRIBUTION
DIVERSIFICATION
GENETICS
INOCULATION
MACACUS
MUTATIONS
PLASMA
RNA
SIMIAN VIRUS
SPECTRA
VIRUSES