title: Restriction of HIV-1 replication in primary macrophages by IL-12 and IL-18 through the upregulation of SAMHD1.
abstract: Monocyte-derived macrophages (MDM) can polarize into different subsets depending on the environment and the activation signal to which they are submitted. Differentiation into macrophages allows HIV-1 strains to infect cells of the monocytic lineage. In this study, we show that culture of monocytes with a combination of IL-12 and IL-18 led to macrophage differentiation that was resistant to HIV-1 infection. In contrast, M-CSF-derived MDM were readily infected by HIV-1. When monocytes were differentiated in the presence of M-CSF and then further treated with IL-12/IL-18, cells became resistant to infection. The restriction on HIV-1 replication was not dependent on virus entry or coreceptor expression, as vesicular stomatitis virus-pseudotyped HIV-1 replication was also blocked by IL-12/IL-18. The HIV-1 restriction factor sterile α motif and HD domain-containing protein-1 (SAMHD1) was significantly overexpressed in IL-12/IL-18 MDM compared with M-CSF MDM, and degradation of SAMHD1 by RNA interference or viral-like particles carrying the lentiviral protein Vpx restored HIV-1 infectivity of IL-12/IL-18 MDM. SAMHD1 overexpression induced by IL-12/IL-18 was not dependent on IFN-γ. Thus, we conclude that IL-12 and IL-18 may contribute to the response against HIV-1 infection through the induction of restriction factors such as SAMHD1.
authors.affiliation: IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pauls
authors.forename: Esther
authors.initials: E
authors.lastname: Jimenez
authors.forename: Alba
authors.initials: A
authors.lastname: Ruiz
authors.forename: Marc
authors.initials: M
authors.lastname: Permanyer
authors.forename: Ester
authors.initials: E
authors.lastname: Ballana
authors.forename: Helena
authors.initials: H
authors.lastname: Costa
authors.forename: Rute
authors.initials: R
authors.lastname: Nascimiento
authors.forename: R Michael
authors.initials: RM
authors.lastname: Parkhouse
authors.forename: Ruth
authors.initials: R
authors.lastname: Peña
authors.forename: Eva
authors.initials: E
authors.lastname: Riveiro-Muñoz
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martinez
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: José A
authors.initials: JA
authors.lastname: Esté
authors.forename: Margarida
authors.initials: M
authors.lastname: Bofill
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000076106:SAM Domain and HD Domain-Containing Protein 1; D015854:Up-Regulation; D014779:Virus Replication / Q000235:genetics*
chemical_list: D020382:Interleukin-18; D018664:Interleukin-12; D016173:Macrophage Colony-Stimulating Factor; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins