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JCI Insight. 2016 Dec 8;1(20):e88255. doi: 10.1172/jci.insight.88255.

IFN-ε protects primary macrophages against HIV infection.

Author information

1
Department of Microbiology, Biochemistry and Molecular Genetics and.
2
Public Health Research Institute, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.
3
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
4
Department of Microbiology, New York University School of Medicine, New York, New York, USA.

Abstract

IFN-ε is a unique type I IFN that is not induced by pattern recognition response elements. IFN-ε is constitutively expressed in mucosal tissues, including the female genital mucosa. Although the direct antiviral activity of IFN-ε was thought to be weak compared with IFN-α, IFN-ε controls Chlamydia muridarum and herpes simplex virus 2 in mice, possibly through modulation of immune response. We show here that IFN-ε induces an antiviral state in human macrophages that blocks HIV-1 replication. IFN-ε had little or no protective effect in activated CD4+ T cells or transformed cell lines unless activated CD4+ T cells were infected with replication-competent HIV-1 at a low MOI. The block to HIV infection of macrophages was maximal after 24 hours of treatment and was reversible. IFN-ε acted on early stages of the HIV life cycle, including viral entry, reverse transcription, and nuclear import. The protection did not appear to operate through known type I IFN-induced HIV host restriction factors, such as APOBEC3A and SAMHD1. IFN-ε-stimulated immune mediators and pathways had the signature of type I IFNs but were distinct from IFN-α in macrophages. IFN-ε induced significant phagocytosis and ROS, which contributed to the block to HIV replication. These findings indicate that IFN-ε induces an antiviral state in macrophages that is mediated by different factors than those induced by IFN-α. Understanding the mechanism of IFN-ε-mediated HIV inhibition through immune modulation has implications for prevention.

PMID:
27942584
PMCID:
PMC5135270
DOI:
10.1172/jci.insight.88255
[Indexed for MEDLINE]
Free PMC Article

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