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

• Type of Material: Article
• Authors: Ling Yue, Emory University; Eric Hunter, Emory University; Susan Allen, Emory University; Etienne Karita, Emory University; Joshua Baalwa, University of Alabama Birmingham; Shuyi Wang, University of Pennsylvania; Nicholas Parrish, University of Pennsylvania; Julie M. Decker, University of Alabama Birmingham; Brandon F. Keele, SAIC Frederick Inc; Gerald H. Learn, University of Pennsylvania; Eugene Ruzagira, Uganda Virus Research Institute; Deogratius Ssemwanga, Uganda Virus Research Institute; Anatoli Kamali, Uganda Virus Research Institute; Pauli N. Amornkul, International AIDS Vaccine Initiative, New York; Matt A. Price, International AIDS Vaccine Initiative, New York; John C. Kappes, University of Alabama Birmingham; Pontiano Kaleebu, Uganda Virus Research Institute; Eduard Sanders, International AIDS Vaccine Initiative, New York; Jill Gilmour, International AIDS Vaccine Initiative, New York; David C. Montefiori, Duke University; Barton F. Haynes, Duke University; Emmanuel Cormier, International AIDS Vaccine Initiative, New York; Beatrice H. Hahn, University of Pennsylvania; George M. Shaw, University of Pennsylvania
• Language: English
• Date: 2013-02-05
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.virol.2012.10.009
• Title of Journal or Parent Work: Virology
• ISSN: 0042-6822
• Volume: 436
• Issue: 1
• Start Page: 33
• End Page: 48
• Grant/Funding Information: This work was supported by grants from the NIH (AI067854 and AI100645), the Bill and Melinda Gates Foundation (37874), and the United States Agency for International Development (GPO-A-00-06-00006-00).
• Keywords: ENVELOPE GLYCOPROTEINS; Single genome sequencing; Virology; HIV-1 subtype D; CORECEPTOR TROPISM; HUMAN-IMMUNODEFICIENCY-VIRUS; FASTER DISEASE PROGRESSION; HETEROSEXUAL TRANSMISSION; Science & Technology; GENOTYPIC CHARACTERISTICS; TYPE-1 SUBTYPE; NEUTRALIZING ANTIBODIES; Life Sciences & Biomedicine; Transmitted/founder virus; 2ND CODING EXON; GP41 CYTOPLASMIC TAIL; HIV-1 subtype A; HIV-1 transmission; Neutralizing antibodies; HIV-1
• Research Categories: Biology, Virology; Chemistry, Biochemistry; Health Sciences, Immunology

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.