ENHANCED IN-VITRO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION IN B-CELLS EXPRESSING SURFACE ANTIBODY TO THE TM ENV PROTEIN

The human immunodeficiency virus type 1 (HIV-1) external envelope glyc oprotein gp120 tightly binds CD4 as its principal cellular receptor, e xplaining the tropism of HIV-1 for CD4(+) cells. Nevertheless, reports documenting HIV infection or HIV binding in cells lacking CD4 surface expression have raised the possibility that cellular receptors in add ition to CD4 mag interact with HIV envelope. Moreover, the lymphocyte adhesion molecule LFA-1 appears to play an important role in augmentin g HIV-1 viral spread and cytopathicity in vitro, although the mechanis m of this function is still not completely defined. In the course of c haracterizing a human anti-HN gp41 monoclonal antibody, we transfected a CD4-negative, LFA-1-negative B cell line to express an anti-gp41 im munoglobulin receptor (surface immunoglobulin [sIg]/gp41). Despite acq uiring the ability to bind HIV envelope, such transfected B cells coul d not be infected by HIV-1. These cells were not intrinsically defecti ve for supporting HIV-1 infection, because when directed to produce su rface CD4 by using retroviral constructs, they acquired the ability to replicate HIV-1. Interestingly, transfected cells expressing both sur face CD4 and sIg/gp41 receptors replicated HIV much better than cells expressing only CD4. The enhancement resided specifically in sIg/gp41, because isotype-specific, anti-IgG1 antibodies directed against sIg/g p41 blocked the enhancement. These data directly establish the ability of a cell surface anti-gp41 receptor to enhance HIV-1 replication.