4.4 Article

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

Journal

VIROLOGY
Volume 436, Issue 1, Pages 33-48

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2012.10.009

Keywords

HIV-1; Transmitted/founder virus; Single genome sequencing; HIV-1 transmission; HIV-1 subtype A; HIV-1 subtype D; Neutralizing antibodies

Categories

Funding

  1. NIH [AI067854, AI100645]
  2. Bill and Melinda Gates Foundation [37874]
  3. United States Agency for International Development [GPO-A-00-06-00006-00]
  4. MRC [MC_U950097144, MC_U950080938] Funding Source: UKRI
  5. Medical Research Council [MC_U950080938, MC_U950097144] Funding Source: researchfish

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We report the molecular identification, cloning and initial biological characterization of 12 full-length HIV-1 subtype A, D and AID recombinant transmitted/founder (T/F) genomes. T/F genomes contained intact canonical open reading frames and all TIP 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. (C) 2012 Elsevier Inc. All rights reserved.

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