title: Interleukin-27 is a potent inhibitor of cis HIV-1 replication in monocyte-derived dendritic cells via a type I interferon-independent pathway.
abstract: IL-27, a member of the IL-12 family of cytokines, plays an important and diverse role in the function of the immune system. Whilst generally recognized as an anti-inflammatory cytokine, in addition IL-27 has been found to have broad anti-viral effects. Recently, IL-27 has been shown to be a potent inhibitor of HIV-1 infection in CD4+ T cells and macrophages. The main objective of this study was to see whether IL-27 has a similar inhibitory effect on HIV-1 replication in dendritic cells (DCs). Monocytes were differentiated into immature DCs (iDCs) and mature DCs (mDCs) with standard techniques using a combination of GM-CSF, IL-4 and LPS. Following differentiation, iDCs were infected with HIV-1 and co-cultured in the presence or absence of IL-27. IL-27 treated DCs were shown to be highly potent inhibitors of cis HIV-1, particularly of CCR5 tropic strains. Of note, other IL-12 family members (IL-12, IL-23 and IL-35) had no effect on HIV-1 replication. Microarray studies of IL-27 treated DCs showed no up-regulation of Type I (IFN) gene expression. Neutralization of the Type-I IFN receptor had no impact on the HIV inhibition. Lastly, IL-27 mediated inhibition was shown to act post-viral entry and prior to completion of reverse transcription. These results show for the first time that IL-27 is a potent inhibitor of cis HIV-1 infection in DCs by a Type I IFN independent mechanism. IL-27 has previously been reported to inhibit HIV-1 replication in CD4+ T cells and macrophages, thus taken together, this cytokine is a potent anti-HIV agent against all major cell types targeted by the HIV-1 virus and may have a therapeutic role in the future.
authors.affiliation: Applied and Developmental Research Directorate (ADD), Science Application International Corporation (SAIC)-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Sanjay
authors.initials: S
authors.lastname: Swaminathan
authors.forename: De
authors.initials: D
authors.lastname: Yang
authors.forename: Lue
authors.initials: L
authors.lastname: Dai
authors.forename: Hongyan
authors.initials: H
authors.lastname: Sui
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hornung
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Wang
authors.forename: Da Wei
authors.initials: da W
authors.lastname: Huang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Hu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.forename: Tomozumi
authors.initials: T
authors.lastname: Imamichi
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D020381:Interleukin-17 / Q000494:pharmacology*; D046228:Microarray Analysis; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D016207:Cytokines; D007370:Interferon Type I; D020381:Interleukin-17