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: Eduardo Pauls, Esther Jimenez, Alba Ruiz, Marc Permanyer, Ester Ballana, Helena Costa, Rute Nascimiento, R Michael Parkhouse, Ruth Peña, Eva Riveiro-Muñoz, Miguel A Martinez, Bonaventura Clotet, José A Esté, Margarida Bofill
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 190 Issue 9 Pg. 4736-41 (May 01 2013) ISSN: 1550-6606 [Electronic] United States
• PMID: 23526823 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-18
• Interleukin-12
• Macrophage Colony-Stimulating Factor
• SAM Domain and HD Domain-Containing Protein 1
• SAMHD1 protein, human
• Monomeric GTP-Binding Proteins

Topics

• Cell Differentiation (genetics)
• HIV-1 (genetics, metabolism, physiology)
• Humans
• Interleukin-12 (genetics, immunology, metabolism)
• Interleukin-18 (genetics, immunology, metabolism)
• Macrophage Colony-Stimulating Factor (genetics, immunology, metabolism)
• Macrophages (immunology, metabolism, virology)
• Monocytes (immunology, metabolism, virology)
• Monomeric GTP-Binding Proteins (genetics, immunology, metabolism)
• SAM Domain and HD Domain-Containing Protein 1
• Up-Regulation
• Virus Replication (genetics)