Inhibition of human immunodeficiency virus type 1 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. Because HIV replication is dependent on cellular activation, immunosuppressive cytokines that deactivate macrophages and T cells may be important modulators of an antiviral effect. We tested the anti-HIV potential of the immunosuppressive cytokine-transforming growth factor beta (TGF-beta 1) alone and in combination with AZT in a new monomyeloblastic 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 HIV-1-specific mRNA. TGF-beta 1 as a single agent had no effect on the multiplication of HIV-IIIB in de novo-infected PLB 985 monomyeloblastic cells. However, cotreatment with TGF-beta 1 and AZT synergistically slowed virus multiplication within the first week following infection, as determined by reverse transcriptase measurement, p24 antigen detection, and northern blot analysis of viral RNA. The synergistic actions of TGF-beta 1 and AZT were also observed in PLB 985 cells infected with an AZT-resistant strain of HIV-1 (HIV 1393). Synergism between nucleoside analogs and cytokines may be an important therapeutic approach to HIV-1 infection. Elucidation of the role of cytokines in controlling the degree of HIV multiplication may have an impact on both clinical treatments and understanding the progression to AIDS.