title: IL-27 inhibits HIV-1 infection in human macrophages by down-regulating host factor SPTBN1 during monocyte to macrophage differentiation.
abstract: 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.
authors: Applied and Developmental Directorate, Science Applications International Corporation-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors: Lue
authors: L
authors: Dai
authors: Kristy B
authors: KB
authors: Lidie
authors: Qian
authors: Q
authors: Chen
authors: Joseph W
authors: JW
authors: Adelsberger
authors: Xin
authors: X
authors: Zheng
authors: DaWei
authors: D
authors: Huang
authors: Jun
authors: J
authors: Yang
authors: Richard A
authors: RA
authors: Lempicki
authors: Tauseef
authors: T
authors: Rehman
authors: Robin L
authors: RL
authors: Dewar
authors: Yanmei
authors: Y
authors: Wang
authors: Ronald L
authors: RL
authors: Hornung
authors: Kelsey A
authors: KA
authors: Canizales
authors: Stephen J
authors: SJ
authors: Lockett
authors: H Clifford
authors: HC
authors: Lane
authors: Tomozumi
authors: T
authors: Imamichi
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007378:Interleukins / Q000494:pharmacology*; D020930:MAP Kinase Kinase Kinases / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000821:virology*; D009000:Monocytes / Q000166:cytology*; D020559:Monomeric GTP-Binding Proteins / Q000502:physiology; D000076106:SAM Domain and HD Domain-Containing Protein 1; D013049:Spectrin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D019380:Anti-HIV Agents; D007378:Interleukins; D020930:MAP Kinase Kinase Kinases; D020559:Monomeric GTP-Binding Proteins; D000076106:SAM Domain and HD Domain-Containing Protein 1; D013049:Spectrin; D054301:gag Gene Products, Human Immunodeficiency Virus; D000099151:MAP Kinase Kinase Kinase 7; C464565:MYDGF protein, human; C452439:SPTBN1 protein, human; C484280:SAMHD1 protein, human