Seth P, Wasson DB, Carson DA, Lotz M; International Conference on AIDS.
Int Conf AIDS. 1991 Jun 16-21; 7: 164 (abstract no. W.A.1290).
University of California, San Diego, La Jolla, CA 92093-0945 USA
We recently reported that transforming growth factor-beta (TGFbeta) is overexpressed in HIV infection and that this cytokine contributes to immune defects through a noncytopathic mechanism. It was then shown that TGFbeta and the HIV regulatory protein tat have similar effects on cell functions and that tat can induce TGFbeta production. The present study characterizes the effects of HIV tat, and TGFbeta, on peripheral blood monocyte-derived macrophage activation, and on virus replication. The addition of recombinant or synthetic HIV-1 tat or TGFbeta to human monocyte-derived macrophages that were infected with vaccinia virus (VV) resulted in 2-3 fold enhanced viral yield. VV replication was reduced by IFNgamma, and tat antagonized the antiviral effects of IFNgamma. Additional effects of IFNgamma that are important in host defense responses include macrophage activation, a process that correlates with increased neopterin synthesis and the induction of HLA Class II antigens. These functions were also inhibited in a dose-dependent fashion by HIV tat and in these as well as in the antiviral assays TGFbeta had qualitatively similar effects as tat. In contrast to these inhibitory effects, both tat and TGFbeta enhanced monocyte expression of the Fc receptor, CD16, thereby indicating that macrophage functions are differentially regulated by these agents. These results show that HIV tat has effects similar to TGFbeta, a potent immunosuppressive cytokine. Thus, both tat and TGFbeta block IFNgamma-induced activation and antiviral activity in macrophages, and enhance virus replication and CD16 expression. These findings provide a novel mechanism for interference with antiviral immune responses in HIV infection.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Antiviral Agents
- Gene Products, tat
- Genes, tat
- HIV Infections
- HIV Seropositivity
- HIV-1
- Humans
- Macrophage Activation
- Macrophages
- Monocytes
- Motor Activity
- Transforming Growth Factor beta
- Virus Replication
- genetics
- immunology
- virology
Other ID:
UI: 102192497
From Meeting Abstracts