Human immunodeficiency virus-1 infection requires pertussis toxin sensitive G-protein-coupled signalling and mediates cAMP downregulation

The human immunodeficiency virus-1 (HIV-1) utilises CD4 and certain beta-ch emokine receptors, mainly CCR-5 and CXCR4, for attachment and virus entry i nto T-lymphocytes and monocytes/maerophages. CD4 and beta-chemokine recepto rs participate in intracellular signalling via protein tyrosine kinases and G-protein-coupled signalling, The factors which influence HIV-1 replicatio n and the intracellular signalling mechanisms elicited by the virus are not well understood. In this study, it was demonstrated that exposure of perip heral blood lymphocytes (PBLs) to a T-cell tropic strain of HIV-1 evokes si gnal(s) which results in downregulation of intracellular cAMP. In addition, preincubation of PBLs with the G(i)-protein inhibitor Pertussis toxin medi ated a significant inhibition of HIV-1 replication. These data strongly sug gest that HIV-1 employs CD4 receptors and Gi-coupled proteins for entry int o target cells and that productive HIV-1 infection is dependent on an activ e signalling event. (C) 1999 Academic Press.