DISTINCT EFFECTS IN PRIMARY MACROPHAGES AND LYMPHOCYTES OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACCESSORY GENES VPR, VPU, AND NEF - MUTATIONAL ANALYSIS OF A PRIMARY HIV-1 ISOLATE

Macrophages and lymphocytes are the two main targets for productive HI V-1 infection in vivo. To compare the effects of the ''nonessential'' HIV-1 accessory genes vpr, vpu, and nef on Viral replication in these primary cell types, we generated a panel of mutant viruses derived fro m a molecularly cloned macrophage-tropic HIV-1 primary isolate. Mutant viruses had markedly different patterns of replication in macrophages , in contrast to lymphocytes in which differences were modest. Loss of vpr or vpu reduced viral antigen production in macrophages by up to 1 000-fold, while replication in lymphocytes was only marginally affecte d. Loss of nef did not affect lymphocyte infection, but decreased repl ication in macrophages to a small extent. Mutation of multiple accesso ry genes restricted replication in both cell types, but to a much grea ter extent in macrophages, and frequently resulted in nonproductive in fection. The degree to which replication depended on intact accessory genes varied in macrophages from different donors. The essential funct ions of these accessory genes in HIV-1 infection may be related to the ir combined effects in facilitating productive infection of macrophage s. (C) 1994 Academic Press, Inc.