INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-I MULTIPLICATION BY TRANSFORMING GROWTH-FACTOR BETA(1) AND AZT IN HIV-1-INFECTED MYELOID CELLS

Myeloid cells are important reservoirs of HIV-1 infection, In response to pathogenic agents, macrophages secrete inflammatory cytokines that can modulate viral replication and contribute to AIDS pathogenesis, B ecause HIV replication Is dependent on cellular activation, immunosupp ressive cytokines that deactivate macrophages and T cells may be impor tant modulators of an antiviral effect, We tested the anti-HIV potenti al of the immunosuppressive cytokine-transforming growth factor beta ( TGF-beta(1)) alone and in combination with AZT in a new monomyeloblast ic model of HIV-1 infection, The PLB-985 cell model was infected with HIV IIIB strain, and the course of HIV-1 infection and replication was monitored by reverse transcriptase assay, p24 immunofluorescence, and northern blot analysis of HN-l-specific mRNA, TGF-beta(1) as a single agent had no effect on the multiplication of HIV-IIIB in de novo-infe cted PLB 985 monomyeloblastic cells, However, cotreatment with TGF-bet a(1) and AZT synergistically slowed virus multiplication within the fi rst week following infection, as determined by reverse transcriptase m easurement, p24 antigen detection, and northern blot analysis of viral RNA, The synergistic actions of TGF-beta(1) and AZT were also observe d in PLB 985 cells infected with an AZT-resistant strain of HIV-1 (HN 1393), Synergism between nucleoside analogs and cytokines may be an im portant therapeutic approach to HIV-1 infection, Elucidation of the ro le of cytokines in controlling the degree of HIV multiplication may ha ve an impact on both clinical treatments and understanding the progres sion to AIDS.