title: The replication of human immunodeficiency virus type 1 in macrophages is enhanced after phagocytosis of apoptotic cells.
abstract: 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.
authors.affiliation: Laboratório Avançado de Saúde Pública, Instituto de Investigação em Imunologia, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Universidade Federal da Bahia, Salvador, Brazil. rosangela@cpqgm.fiocruz.br
authors.forename: Rosangela G
authors.initials: RG
authors.lastname: Lima
authors.forename: Johan
authors.initials: J
authors.lastname: Van Weyenbergh
authors.forename: Elvira M B
authors.initials: EM
authors.lastname: Saraiva
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
authors.forename: Bernardo
authors.initials: B
authors.lastname: Galvão-Castro
authors.forename: Dumith Chequer
authors.initials: DC
authors.lastname: Bou-Habib
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D010587:Phagocytosis; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014779:Virus Replication
chemical_list: C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1