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Journal of Clinical Microbiology, February 2000, p. 773-780, Vol. 38, No. 2
0095-1137/00/$04.00+0

Analysis of Genetic Variability within the Immunodominant Epitopes of Envelope gp41 from Human Immunodeficiency Virus Type 1 (HIV-1) Group M and Its Impact on HIV-1 Antibody Detection

Jonathan Dorn,1 Silvina Masciotra,1 Chunfu Yang,1 Robert Downing,2 Benon Biryahwaho,2 Timothy D. Mastro,3 John Nkengasong,4 Danuta Pieniazek,5 Mark A. Rayfield,5 Dale J. Hu,6 and Renu B. Lal1,*

HIV Immunology and Diagnostics Branch,1 and HIV and Retroviruses Diseases Branch,5 Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, and International Activities Branch, Division of HIV/AIDS Prevention-Surveillance and Epidemiology Branch, National Center for HIV, STD and TB Prevention,6 Centers for Disease Control and Prevntion, Atlanta, Georgia 30333; Uganda Virus Research Institute, Entebbe, Uganda2; HIV/AIDS Collaboration, Nonthaburi, Thailand3; and Projet RETRO-CI, Abidjan, Côte d'Ivoire4

Received 26 August 1999/Returned for modification 11 October 1999/Accepted 11 November 1999

The serodiagnosis of human immunodeficiency virus type 1 (HIV-1) infection primarily relies on the detection of antibodies, most of which are directed against the immunodominant regions (IDR) of HIV-1 structural proteins. Among these, the N-terminal region of gp41 contains cluster I (amino acids [aa] 580 to 623), comprising the cytotoxic T-lymphocyte epitope (AVERYLKDQQLL) and the cysteine loop (CSGKLIC), and cluster II (aa 646 to 682), comprising an ectodomain region (ELDKWA). To delineate the epitope diversity within clusters I and II and to determine whether the diversity affects serologic detection by U.S. Food and Drug Administration (FDA)-licensed enzyme immunoassay (EIA) kits, gp41 Env sequences from 247 seropositive persons infected with HIV-1 group M, subtypes A (n = 42), B (n = 62), B' (n = 13), C (n = 38), D (n = 41), E (n = 18), F (n = 27), and G (n = 6), and 6 HIV-1-infected but persistently seronegative (HIPS) persons were analyzed. While all IDR were highly conserved among both seropositive and HIPS persons, minor amino acid substitutions (<20% for any one residue, mostly conservative) were observed for all subtypes, except for B', in comparison with the consensus sequence for each subtype. Most importantly, none of the observed substitutions among the group M plasma specimens affected antibody detection, since all specimens (n = 152) tested positive with all five FDA-licensed EIA kits. Furthermore, all specimens reacted with a group M consensus gp41 peptide (WGIKQLQARVLAVERYLKDQQLLGIWGCSGKLICTTAVPWNASW), and high degrees of cross-reactivity (>80%) were observed with an HIV-1 group N peptide, an HIV-1 group O peptide, and a peptide derived from the homologous region of gp41 from simian immunodeficiency virus from chimpanzee (SIVcpz). Taken together, these data indicate that the minor substitutions observed within the IDR of gp41 of HIV-1 group M subtypes do not affect antibody recognition and that all HIV-1-seropositive specimens containing the observed substitutions react with the FDA-licensed EIA kits regardless of viral genotype and geographic origin.

* Corresponding author. Mailing address: HIV Immunology and Diagnostics Branch, DASTLR/NCID, Centers for Disease Control and Prevention, Mail Stop D12, 1600 Clifton Rd., Atlanta, GA 30333. Phone: (404) 639-1036. Fax: (404) 639-2660. E-mail: rbl3{at}cdc.gov.

Journal of Clinical Microbiology, February 2000, p. 773-780, Vol. 38, No. 2
0095-1137/00/$04.00+0


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