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Journal of Virology, August 2000, p. 7096-7107, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Conserved and Exposed Epitopes on Intact, Native, Primary Human
Immunodeficiency Virus Type 1 Virions of Group M
Phillipe N.
Nyambi,1
Henry A.
Mbah,1
Sherri
Burda,1
Constance
Williams,1
Miroslaw K.
Gorny,1
Arthur
Nádas,2 and
Susan
Zolla-Pazner1,3,*
Department of
Pathology1 and Institute of
Environmental Medicine,2 New York University
School of Medicine, New York, New York 10016, and Research
Center for AIDS and HIV Infection, VA Medical Center, New York, New
York 100103
Received 1 February 2000/Accepted 4 May 2000
We have examined the exposure and conservation of antigenic
epitopes on the surface envelope glycoproteins (gp120 and gp41) of 26 intact, native, primary human immunodeficiency virus type 1 (HIV-1)
group M virions of clades A to H. For this, 47 monoclonal antibodies
(MAbs) derived from HIV-1-infected patients were used which were
directed at epitopes of gp120 (specifically V2, C2, V3, the CD4-binding
domain [CD4bd], and C5) and epitopes of gp41 (clusters I and II). Of
the five regions within gp120 examined, MAbs bound best to epitopes in
the V3 and C5 regions. Only moderate to weak binding was observed by
most MAbs to epitopes in the V2, C2, and CD4bd regions. Two anti-gp41
cluster I MAbs targeted to a region near the tip of the hydrophilic
immunodominant domain bound strongly to >90% of isolates tested. On
the other hand, binding of anti-gp41 cluster II MAbs was poor to
moderate at best. Binding was dependent on conformational as well as
linear structures on the envelope proteins of the virions. Further
studies of neutralization demonstrated that MAbs that bound to virions
did not always neutralize but all MAbs that neutralized bound to the
homologous virus. This study demonstrates that epitopes in the V3 and
C5 regions of gp120 and in the cluster I region of gp41 are well
exposed on the surface of intact, native, primary HIV-1 isolates and
that cross-reactive epitopes in these regions are shared by many
viruses from clades A to H. However, only a limited number of MAbs to
these epitopes on the surface of HIV-1 isolates can neutralize primary isolates.
*
Corresponding author. Mailing address: Veterans Affairs
Medical Center, 423 E. 23rd St., Room 18124N, New York, NY 10010. Phone: (212) 263-6769. Fax: (212) 951-6321. E-mail:
Zollas01{at}popmail.med.nyu.edu.
Journal of Virology, August 2000, p. 7096-7107, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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