Antibody binding and neutralization of primary and T-cell line-adapted isolates of human immunodeficiency virus type 1.
The relative resistance of human immunodeficiency virus type 1 (HIV-1) primary isolates (PIs) to neutralization by a wide range of antibodies remains a theoretical and practical barrier to the development of an effective HIV vaccine. One model to account for the differential neutralization sensitivity between Pls and laboratory (or T-cell line-adapted [TCLA]) strains of HIV suggests that the envelope protein (Env) complex is made more accessible to antibody binding as a consequence of adaptation to growth in established cell lines. Here, we revisit this question using genetically related PI and TCLA viruses and molecularly cloned env genes. By using complementary techniques of flow cytometry and virion binding assays, we show that monoclonal antibodies targeting the V3 loop, CD4-binding site, CD4-induced determinant of gp120, or the ectodomain of gp41 bind equally well to PI and TCLA Env complexes, despite large differences in neutralization outcome. The data suggest that the differential neutralization sensitivity of PI and TCLA viruses may derive not from differences in the initial antibody binding event but rather from differences in the subsequent functioning of the PI and TCLA Envs during virus entry. An understanding of these as yet undefined differences may enhance our ability to generate broadly neutralizing HIV vaccine immunogens.
Montana Biotechnology Center, The University of Montana, Missoula, Montana 59812, USA.
J
J
York
K E
KE
Follis
M
M
Trahey
P N
PN
Nyambi
S
S
Zolla-Pazner
J H
JH
Nunberg
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D002460:Cell Line; D005434:Flow Cytometry; D015686:Gene Products, env / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000821:virology; D014162:Transfection; D014771:Virion / Q000276:immunology / Q000472:pathogenicity
D000911:Antibodies, Monoclonal; D015686:Gene Products, env; D015483:HIV Antibodies