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Journal of Clinical Microbiology, February 2000, p. 773-780, Vol. 38, No. 2
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.
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
*
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.
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