Show simple item record

dc.contributor.authorKeele, Brandon F.
dc.contributor.authorLearn, Gerald H.
dc.contributor.authorHraber, Peter
dc.contributor.authorGiorgi, Elena E.
dc.contributor.authorGrayson, Truman
dc.contributor.authorSun, Chuanxi
dc.contributor.authorChen, Yalu
dc.contributor.authorMascola, John R.
dc.contributor.authorNabel, Gary J.
dc.contributor.authorHaynes, Barton F.
dc.contributor.authorBhattacharya, Tanmoy
dc.contributor.authorPerelson, Alan S.
dc.contributor.authorKorber, Bette T.
dc.contributor.authorHahn, Beatrice H.
dc.contributor.authorShaw, George M.
dc.contributor.authorLi, Hui
dc.contributor.authorYeh, Wendy Wen-Li
dc.contributor.authorLetvin, Norman Lee
dc.date.accessioned2010-12-08T20:29:23Z
dc.date.issued2009
dc.identifier.citationKeele, Brandon F., Hui Li, Gerald H. Learn, Peter Hraber, Elena E. Giorgi, Truman Grayson, Chuanxi Sun, et al. 2009. Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. Journal of Experimental Medicine 206(5): 1117-1134.en_US
dc.identifier.issn0022-1007en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4621131
dc.description.abstractWe 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.en_US
dc.language.isoen_USen_US
dc.publisherRockefeller University Pressen_US
dc.relation.isversionofdoi: 10.1084/jem.20082831en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715022/pdf/en_US
dash.licenseLAA
dc.titleLow-Dose Rectal Inoculation of Rhesus Macaques by SIVsmE660 or SIVmac251 Recapitulates Human Mucosal Infection by HIV-1en_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalJournal of Experimental Medicineen_US
dash.depositing.authorLetvin, Norman Lee
dc.date.available2010-12-08T20:29:23Z
dash.affiliation.otherHMS^Medicine- Beth Israel-Deaconessen_US
dash.affiliation.otherHMS^Medicine- Beth Israel-Deaconessen_US
dc.identifier.doi10.1084/jem.20082831*
dash.authorsorderedfalse
dash.contributor.affiliatedYeh, Wendy Wen-Li
dash.contributor.affiliatedLetvin, Norman Lee


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record