PMID: 9643373Jun 27, 1998Paper

Neutralizing antibodies directed against the V3 loop select for different escape variants in a virus with mutated reverse transcriptase (M184V) than in wild-type human immunodeficiency virus type 1

AIDS Research and Human Retroviruses
P InouyeM A Wainberg

Abstract

The M184V substitution in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) encodes high-level resistance to the (-)-enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC) and low-level resistance to each of 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI). This mutation also results in decreased HIV replication fitness in primary cells, diminished RT processivity, and increased RT fidelity. To assess the effect of this substitution on genetic variation in the HIV env region, we cultured both M184V-containing and wild-type BH10 in MT-4 cells in the presence of the neutralizing monoclonal antibody 447-52D, targeted to the GPGR epitope within the V3 loop of gp120. Outgrowth of viruses resistant to neutralization was followed by sequence analysis of the V3 loop by standard methodology. Wild-type HIV first showed escape after 15-22 days in culture. Sequence analysis revealed an arginine-to-lysine change within the GPGR epitope in the V3 loop (R20K, AGA --> AAA) in six of six clones sequenced after day 36. In contrast, M184V-containing HIV first showed escape between days 25 and 32 and sequence analysis revealed an aspartate-to-tyrosine change at amino acid 5 in V3 (N5Y; AAC --> TAC) in two of six clones at...Continue Reading

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Citations

Jun 17, 2000·Journal of Virological Methods·S C HsuW J Syu
Aug 28, 2001·AIDS Research and Human Retroviruses·S D'CostaJ L Hurwitz
Feb 15, 2001·AIDS Research and Human Retroviruses·N KochC Tamalet
Oct 25, 2003·Antimicrobial Agents and Chemotherapy·Karidia DialloM A Wainberg
Oct 16, 2004·Expert Review of Anti-infective Therapy·Mark A Wainberg
Nov 13, 2004·Antiviral Chemistry & Chemotherapy·Dan TurnerMark A Wainberg
Nov 11, 2003·Clinical and Diagnostic Laboratory Immunology·Dan TurnerMark A Wainberg

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