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

J Virol. 2011 Sep;85(17):8514-27. doi: 10.1128/JVI.00736-11. Epub 2011 Jun 29.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Dendritic Cells / virology
  • Female
  • HIV Antibodies / immunology*
  • HIV Infections / virology*
  • HIV-1 / immunology*
  • HIV-1 / isolation & purification
  • HIV-1 / pathogenicity*
  • Humans
  • Male
  • Viral Tropism*
  • Virus Internalization
  • env Gene Products, Human Immunodeficiency Virus / immunology*
  • env Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • Antibodies, Neutralizing
  • HIV Antibodies
  • env Gene Products, Human Immunodeficiency Virus