Molecular identification, cloning and characterization of transmitted/founder HIV-1 subtype A, D and A/D infectious molecular clones

Virology. 2013 Feb 5;436(1):33-48. doi: 10.1016/j.virol.2012.10.009. Epub 2012 Nov 1.

Abstract

We report the molecular identification, cloning and initial biological characterization of 12 full-length HIV-1 subtype A, D and A/D recombinant transmitted/founder (T/F) genomes. T/F genomes contained intact canonical open reading frames and all T/F viruses were replication competent in primary human T-cells, although subtype D virus replication was more efficient (p<0.05). All 12 viruses utilized CCR5 but not CXCR4 as a co-receptor for entry and exhibited a neutralization profile typical of tier 2 primary virus strains, with significant differences observed between subtype A and D viruses with respect to sensitivity to monoclonal antibodies VRC01, PG9 and PG16 and polyclonal subtype C anti-HIV IgG (p<0.05 for each). The present report doubles the number of T/F HIV-1 clones available for pathogenesis and vaccine research and extends their representation to include subtypes A, B, C and D.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Cells, Cultured
  • Cloning, Molecular*
  • Female
  • Founder Effect
  • Genome, Viral*
  • HIV Antibodies / immunology
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / classification*
  • HIV-1 / genetics*
  • HIV-1 / immunology
  • Humans
  • Male
  • Open Reading Frames / genetics
  • Receptors, CCR5 / metabolism
  • Sequence Alignment
  • Sequence Analysis, DNA
  • T-Lymphocytes / virology
  • Virus Replication

Substances

  • Antibodies, Monoclonal
  • HIV Antibodies
  • Receptors, CCR5