Conserved and exposed epitopes on intact, native, primary human immunodeficiency virus type 1 virions of group M.
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.
Nyambi
P N
PN
Department of Pathology, New York University School of Medicine, New York, New York 10016, USA.
Mbah
H A
HA
Burda
S
S
Williams
C
C
Gorny
M K
MK
Nádas
A
A
Zolla-Pazner
S
S
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D017124:Conserved Sequence; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011487:Protein Conformation; D014771:Virion / Q000276:immunology* / Q000472:pathogenicity
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41