The envelope gene is a cytopathic determinant of CCR5 tropic HIV-1.
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.
Olivieri
Kevin
K
Department of Microbiology and Myles H. Thaler Center for AIDS and Human Retrovirus Research, University of Virginia, Charlottesville, VA 22908, USA.
Scoggins
Robert M
RM
Bor
Yeou-cherng
YC
Matthews
Aprille
A
Mark
David
D
Taylor
James R
JR
Chernauskas
David
D
Hammarskjöld
Marie-Louise
ML
Rekosh
David
D
Camerini
David
D
D000577:Amides / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D065100:CCR5 Receptor Antagonists; D002460:Cell Line; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D015752:Genes, env; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000502:physiology*; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D009154:Mutation; D009924:Organ Culture Techniques; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000502:physiology; D048348:Reverse Transcription; D013950:Thymus Gland / Q000821:virology; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology*
D000577:Amides; D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D065100:CCR5 Receptor Antagonists; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D000644:Quaternary Ammonium Compounds; D019713:Receptors, CCR5; C119369:TAK 779