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IL-27 inhibits HIV-1 infection in human macrophages by down-regulating host factor SPTBN1 during monocyte to macrophage differentiation
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2013
- Publisher :
- Rockefeller University Press, 2013.
-
Abstract
- IL-27 promotes the differentiation of monocytes to HIV-resistant macrophages by down-regulating host factor SPTBN1.<br />The susceptibility of macrophages to HIV-1 infection is modulated during monocyte differentiation. IL-27 is an anti-HIV cytokine that also modulates monocyte activation. In this study, we present new evidence that IL-27 promotes monocyte differentiation into macrophages that are nonpermissive for HIV-1 infection. Although IL-27 treatment does not affect expression of macrophage differentiation markers or macrophage biological functions, it confers HIV resistance by down-regulating spectrin β nonerythrocyte 1 (SPTBN1), a required host factor for HIV-1 infection. IL-27 down-regulates SPTBN1 through a TAK-1–mediated MAPK signaling pathway. Knockdown of SPTBN1 strongly inhibits HIV-1 infection of macrophages; conversely, overexpression of SPTBN1 markedly increases HIV susceptibility of IL-27–treated macrophages. Moreover, we demonstrate that SPTBN1 associates with HIV-1 gag proteins. Collectively, our results underscore the ability of IL-27 to protect macrophages from HIV-1 infection by down-regulating SPTBN1, thus indicating that SPTBN1 is an important host target to reduce HIV-1 replication in one major element of the viral reservoir.
- Subjects :
- Anti-HIV Agents
medicine.medical_treatment
Cellular differentiation
Immunology
Down-Regulation
Biology
gag Gene Products, Human Immunodeficiency Virus
Article
Monocytes
SAM Domain and HD Domain-Containing Protein 1
Downregulation and upregulation
medicine
Humans
Immunology and Allergy
Macrophage
Monomeric GTP-Binding Proteins
Host factor
Gene knockdown
Interleukins
Macrophages
Monocyte
Spectrin
virus diseases
Cell Differentiation
MAP Kinase Kinase Kinases
Cell biology
medicine.anatomical_structure
Cytokine
Monocyte differentiation
HIV-1
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 210
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....3b0bb35f78a37605327416b174ece37c