Identification of full-length transmitted/founder viruses and their progeny in primary HIV-1 infection

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Identification of transmitted/founder virus genomes and their progeny by is a novel strategy for probing the molecular basis of HIV-1 transmission and for evaluating the genetic imprint of viral and host factors that act to constrain or facilitate virus replication. Here, we show in a cohort of twelve acutely infected subjects (9 clade B; 3 clade C), that complete genomic sequences of transmitted/founder viruses could be inferred using single genome amplification of plasma viral RNA, direct amplicon sequencing, and a model of random virus evolution. This allowed for the precise identification, chemical synthesis, molecular cloning, and biological analysis of those ... continued below

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Korber, Bette; Hraber, Peter; Giorgi, Elena & Bhattacharya, T January 1, 2009.

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Identification of transmitted/founder virus genomes and their progeny by is a novel strategy for probing the molecular basis of HIV-1 transmission and for evaluating the genetic imprint of viral and host factors that act to constrain or facilitate virus replication. Here, we show in a cohort of twelve acutely infected subjects (9 clade B; 3 clade C), that complete genomic sequences of transmitted/founder viruses could be inferred using single genome amplification of plasma viral RNA, direct amplicon sequencing, and a model of random virus evolution. This allowed for the precise identification, chemical synthesis, molecular cloning, and biological analysis of those viruses actually responsible for productive clinical infection and for a comprehensive mapping of sequential viral genomes and proteomes for mutations that are necessary or incidental to the establishment of HIV-1 persistence. Transmitted/founder viruses were CD4 and CCR5 tropic, replicated preferentially in activated primary T-Iymphocytes but not monocyte-derived macrophages, and were effectively shielded from most heterologous or broadly neutralizing antibodies. By 3 months of infection, the evolving viral quasispecies in three subjects showed mutational fixation at only 2-5 discreet genomic loci. By 6-12 months, mutational fixation was evident at 18-27 genomic loci. Some, but not all, of these mutations were attributable to virus escape from cytotoxic Tlymphocytes or neutralizing antibodies, suggesting that other viral or host factors may influence early HIV -1 fitness.

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  • Journal Name: Journal of Experimental Medicine

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  • Report No.: LA-UR-09-00147
  • Report No.: LA-UR-09-147
  • Grant Number: AC52-06NA25396
  • Office of Scientific & Technical Information Report Number: 956487
  • Archival Resource Key: ark:/67531/metadc930043

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Office of Scientific & Technical Information Technical Reports

Reports, articles and other documents harvested from the Office of Scientific and Technical Information.

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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, 3:57 p.m.

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Korber, Bette; Hraber, Peter; Giorgi, Elena & Bhattacharya, T. Identification of full-length transmitted/founder viruses and their progeny in primary HIV-1 infection, article, January 1, 2009; [New Mexico]. (digital.library.unt.edu/ark:/67531/metadc930043/: accessed November 19, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.