Anti-idiotypic antibody to the V3 domain of gp120 binds to vimentin: a possible role of intermediate filaments in the early steps of HIV-1 infection cycle.
Although the CD4 molecule is the major cellular receptor for human immunodeficiency virus (HIV), several lines of evidence suggest participation of additional molecules that are engaged after the binding of HIV to the CD4 receptor and that may facilitate viral entry into the target cell. Some of the post-CD4 binding, perfusion events involve the third hypervariable region (V3 loop) of the viral envelope protein gp120. To identify cellular proteins that interact with the V3 loop, we chose as a probe an antiidiotypic monoclonal antibody (MAb), anti-id2, which was prepared against the neutralizing MAb 110.4 that binds the V3 domain in the envelope glycoprotein gp120 of the LAI isolate of HIV-1. Anti-id2 reacted specifically with a 55- to 60-kDa protein in human T cell and monocytoid cell lines, and in a mouse melanoma cell line. This protein was identified immunologically and by protein sequence analysis as vimentin, an intermediate filament protein of lymphoid and other cells of mesodermal origin. Antiserum raised against vimentin inhibited nuclear translocation of HIV-1 DNA following infection of monocytes and CD4+ T cells with live virus, and reduced the amount of HIV-1 gag-specific RNA in the nuclei of monocytes following inoculation with HIV-1 pseudovirions. These data suggest that vimentin may participate in the early steps of HIV-1 replication, perhaps during the uptake of HIV-1 preintegration complexes into the nuclear compartment.
Thomas
E K
EK
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
Connelly
R J
RJ
Pennathur
S
S
Dubrovsky
L
L
Haffar
O K
OK
Bukrinsky
M I
MI
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D002461:Cell Line, Transformed; D004279:DNA, Viral / Q000378:metabolism; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007382:Intermediate Filaments / Q000276:immunology; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology*; D011233:Precipitin Tests; D014746:Vimentin / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D014746:Vimentin