ANTIIDIOTYPIC 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 imm unodeficiency virus (HIV), several lines of evidence suggest participa tion of additional molecules that are engaged after the binding of HIV to the CD4 receptor and that may facilitate viral entry into the targ et cell. Some of the post-CD4 binding, prefusion events involve the th ird hypervariable region (V3 loop) of the viral envelope protein gp120 . To identify cellular proteins that interact with the V3 loop, we cho se as a probe an antiidiotypic monoclonal antibody (MAb), anti-id2, wh ich 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. Th is protein was identified immunologically and by protein sequence anal ysis as vimentin, an intermediate filament protein of lymphoid and oth er cells of mesodermal origin. Antiserum raised against vimentin inhib ited nuclear translocation of HIV-1 DNA following infection of monocyt es and CD4(+) T cells with live virus, and reduced the amount of HIV-1 gag-specific RNA in the nuclei of monocytes following inoculation wit h HIV-1 pseudovirions. These data suggest that vimentin may participat e in the early steps of HIV-1 replication, perhaps during the uptake o f HIV-1 preintegration complexes into the nuclear compartment.