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J Infect Dis. 2002 Jun 1;185(11):1561-6. Epub 2002 May 17.

The replication of human immunodeficiency virus type 1 in macrophages is enhanced after phagocytosis of apoptotic cells.

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Laboratório Avançado de Saúde Pública, Instituto de Investigação em Imunologia, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Universidade Federal da Bahia, Salvador, Brazil.


Clearance of apoptotic cells increases macrophage secretion of antiinflammatory mediators and might modulate viral replication in human immunodeficiency virus (HIV) type 1-infected macrophages. To study this, primary macrophages were infected with HIV-1 and exposed to apoptotic cells. It was found that phagocytosis of apoptotic cells potently enhanced HIV-1 growth. The peptide Arg-Gly-Asp-Ser, which binds to integrin receptors, inhibited the uptake of apoptotic cells and the subsequent enhancement of HIV-1 replication. Viral replication was preceded by increased secretion of transforming growth factor (TGF)-beta1 and partially reverted by anti-TGF-beta1 antibodies. Moreover, anti-TGF-beta1 antibodies inhibited HIV-1 replication in macrophages not exposed to apoptotic cells. A positive correlation was observed between TGF-beta1 production and HIV-1 growth, and the addition of TGF-beta1 amplified HIV-1 replication in macrophages from low TGF-beta1 producers. The findings suggest that TGF-beta1 favors HIV-1 replication in macrophages and that the clearance of apoptotic cells by HIV-1-infected macrophages contributes to persistent viremia in patients infected with HIV-1.

[Indexed for MEDLINE]

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