CELLULAR ADHERENCE ENHANCES HIV REPLICATION IN MONOCYTIC CELLS

Cellular adherence is important for monocyte migration and function an d is known to induce monocyte activation, leading to the production of mRNA for several protooncogenes and cytokines. In addition, since cel lular adherence has important intracellular signalling function, it ha s the potential to enhance human immunodeficiency virus (HIV) replicat ion in monocytic cells. We have investigated the effects of adhesion o f the monocytic cell line THP-1 transfected with HIV1 or HIV2 long ter minal repeat chloramphenicol acetyltransferase (LTR CAT) constructs. T hese studies have shown that adherence to tissue culture plastic or co nfluent endothelial cells is essential for enhanced HIV LTR CAT expres sion in lipopolysaccharide-stimulated cells. In addition, we have inve stigated the effects of engagement of specific adhesion molecules, usi ng immobilized antibodies, on HIV replication in the promonocytic cell line OM101, which contains a single latent proviral copy of HIV. Such studies have demonstrated that engagement of CD18, the beta subunit o f the lymphocyte function-related antigen-1 (LFA-1) and major histocom patibility complex class II (MHC II) enhanced HIV replication. LFA-1 i s involved in both monocyte-endothelial cell interactions and monocyte -T-cell interactions, and MHC II is involved in monocyte interaction w ith antigen-specific T cells. These data suggest that such interaction s of membrane adhesion molecules with their appropriate ligand enhance HIV replication in vivo. Thus, this study has demonstrated that cellu lar adherence is a key regulatory factor of HIV replication in monocyt ic cells.