Phenotypic and immunologic comparison of clade B transmitted/founder and chronic HIV-1 envelope glycoproteins.

Published

Journal Article

Sexual transmission of human immunodeficiency virus type 1 (HIV-1) across mucosal barriers is responsible for the vast majority of new infections. This relatively inefficient process results in the transmission of a single transmitted/founder (T/F) virus, from a diverse viral swarm in the donor, in approximately 80% of cases. Here we compared the biological activities of 24 clade B T/F envelopes (Envs) with those from 17 chronic controls to determine whether the genetic bottleneck that occurs during transmission is linked to a particular Env phenotype. To maximize the likelihood of an intact mucosal barrier in the recipients and to enhance the sensitivity of detecting phenotypic differences, only T/F Envs from individuals infected with a single T/F variant were selected. Using pseudotyping to assess Env function in single-round infectivity assays, we compared coreceptor tropism, CCR5 utilization efficiencies, primary CD4(+) T cell subset tropism, dendritic cell trans-infections, fusion kinetics, and neutralization sensitivities. T/F and chronic Envs were phenotypically equivalent in most assays; however, T/F Envs were modestly more sensitive to CD4 binding site antibodies b12 and VRC01, as well as pooled human HIV Ig. This finding was independently validated with a panel of 14 additional chronic HIV-1 Env controls. Moreover, the enhanced neutralization sensitivity was associated with more efficient binding of b12 and VRC01 to T/F Env trimers. These data suggest that there are subtle but significant structural differences between T/F and chronic clade B Envs that may have implications for HIV-1 transmission and the design of effective vaccines.

Full Text

Duke Authors

Cited Authors

  • Wilen, CB; Parrish, NF; Pfaff, JM; Decker, JM; Henning, EA; Haim, H; Petersen, JE; Wojcechowskyj, JA; Sodroski, J; Haynes, BF; Montefiori, DC; Tilton, JC; Shaw, GM; Hahn, BH; Doms, RW

Published Date

  • September 2011

Published In

Volume / Issue

  • 85 / 17

Start / End Page

  • 8514 - 8527

PubMed ID

  • 21715507

Pubmed Central ID

  • 21715507

Electronic International Standard Serial Number (EISSN)

  • 1098-5514

Digital Object Identifier (DOI)

  • 10.1128/JVI.00736-11

Language

  • eng

Conference Location

  • United States