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- Title
Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection.
- Authors
Salazar-Gonzalez, Jesus F; Salazar, Maria G; Keele, Brandon F; Learn, Gerald H; Giorgi, Elena E; Li, Hui; Decker, Julie M; Wang, Shuyi; Baalwa, Joshua; Kraus, Matthias H; Parrish, Nicholas F; Shaw, Katharina S; Guffey, M Brad; Bar, Katharine J; Davis, Katie L; Ochsenbauer-Jambor, Christina; Kappes, John C; Saag, Michael S; Cohen, Myron S; Mulenga, Joseph; Derdeyn, Cynthia A; Allen, Susan; Hunter, Eric; Markowitz, Martin; Hraber, Peter; Perelson, Alan S; Bhattacharya, Tanmoy; Haynes, Barton F; Korber, Bette T; Hahn, Beatrice H; Shaw, George M
- Abstract
Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 acutely infected subjects (9 clade B and 3 clade C) that complete HIV-1 genomes of transmitted/founder viruses can be inferred by single genome amplification and sequencing of plasma virion RNA. This allowed for the molecular cloning and biological analysis of transmitted/founder viruses and a comprehensive genome-wide assessment of the genetic imprint left on the evolving virus quasispecies by a composite of host selection pressures. Transmitted viruses encoded intact canonical genes (gag-pol-vif-vpr-tat-rev-vpu-env-nef) and replicated efficiently in primary human CD4(+) T lymphocytes but much less so in monocyte-derived macrophages. Transmitted viruses were CD4 and CCR5 tropic and demonstrated concealment of coreceptor binding surfaces of the envelope bridging sheet and variable loop 3. 2 mo after infection, transmitted/founder viruses in three subjects were nearly completely replaced by viruses differing at two to five highly selected genomic loci; by 12-20 mo, viruses exhibited concentrated mutations at 17-34 discrete locations. These findings reveal viral properties associated with mucosal HIV-1 transmission and a limited set of rapidly evolving adaptive mutations driven primarily, but not exclusively, by early cytotoxic T cell responses.
- Publication
The Journal of experimental medicine, 2009, Vol 206, Issue 6, p1273
- ISSN
1540-9538
- Publication type
Journal Article
- DOI
10.1084/jem.20090378