Unknown

Dataset Information

0

Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection.


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.

SUBMITTER: Salazar-Gonzalez JF 

PROVIDER: S-EPMC2715054 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection.

Salazar-Gonzalez Jesus F JF   Salazar Maria G MG   Keele Brandon F BF   Learn Gerald H GH   Giorgi Elena E EE   Li Hui H   Decker Julie M JM   Wang Shuyi S   Baalwa Joshua J   Kraus Matthias H MH   Parrish Nicholas F NF   Shaw Katharina S KS   Guffey M Brad MB   Bar Katharine J KJ   Davis Katie L KL   Ochsenbauer-Jambor Christina C   Kappes John C JC   Saag Michael S MS   Cohen Myron S MS   Mulenga Joseph J   Derdeyn Cynthia A CA   Allen Susan S   Hunter Eric E   Markowitz Martin M   Hraber Peter P   Perelson Alan S AS   Bhattacharya Tanmoy T   Haynes Barton F BF   Korber Bette T BT   Hahn Beatrice H BH   Shaw George M GM  

The Journal of experimental medicine 20090601 6


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 biologic  ...[more]

Similar Datasets

| S-EPMC2976391 | biostudies-literature
| S-EPMC6922402 | biostudies-literature
| S-EPMC10208420 | biostudies-literature
| S-EPMC3637789 | biostudies-literature
| S-EPMC5908066 | biostudies-literature
| S-EPMC6893788 | biostudies-literature
| S-EPMC4280322 | biostudies-literature
| S-EPMC5899188 | biostudies-literature
| S-EPMC2387184 | biostudies-literature
| S-EPMC5067802 | biostudies-literature