The envelope gene is a cytopathic determinant of CCR5 tropic HIV-1

• Published in: Virology (New York, N.Y.) Vol. 358; no. 1; pp. 23 - 38
• Main Authors: Olivieri, Kevin, Scoggins, Robert M, Bor, Yeou-cherng, Matthews, Aprille, Mark, David, Taylor, James R, Chernauskas, David, Hammarskjöld, Marie-Louise, Rekosh, David, Camerini, David
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.02.2007
• Subjects: Amides - pharmacology; Anti-HIV Agents - pharmacology; Antibodies, Monoclonal - immunology; CCR5; CCR5 Receptor Antagonists; Cell Line; Cells, Cultured; Cytopathogenic Effect, Viral; env; Fetal thymic organ culture; Genes, env; HIV Envelope Protein gp120 - genetics; HIV Envelope Protein gp120 - physiology; HIV Envelope Protein gp41 - genetics; HIV Envelope Protein gp41 - physiology; HIV-1 - genetics; HIV-1 - pathogenicity; Human immunodeficiency virus 1; Humans; Infectious Disease; Mutation; Organ Culture Techniques; Quaternary Ammonium Compounds - pharmacology; R5 HIV-1; Receptors, CCR5 - physiology; Reverse Transcription; SCID-hu mice; Thymocyte; Thymus Gland - virology; Viral Load; Virus Replication - physiology; Fetal thymic organ culture; R5 HIV-1; SCID-hu mice; env; CCR5; Thymocyte
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2006.08.027

Abstract Late stage AIDS associated CCR5 tropic HIV-1 clones (R5-AIDS HIV-1) exhibit greater cytopathic effects (CPE) than earlier isolates from the same patients. In this study, envelopes from a series of three biological clones derived from the same patient were evaluated as a cytopathic determinant of R5-AIDS HIV-1 for thymocytes. In a single round of replication in thymocytes, the AIDS associated clone mediated greater initiation of reverse transcription. This enhancement was not due to broadened coreceptor tropism, as all clones studied were exclusively R5 tropic. The full-length R5-AIDS env mediated greater infectivity than R5 pre-AIDS env when used to pseudotype a reporter virus. R5-AIDS env pseudotypes were more resistant to TAK-779 and showed more rapid infection kinetics but similar resistance to a CD4 blocking mAb. We conclude that the enhanced thymic replication and CPE shown by the R5-AIDS clone is due to enhanced efficiency of Env-mediated entry via CCR5.