IFN-?3 inhibits HIV infection of macrophages through the JAK-STAT pathway.

ABSTRACT: Interferon lambda 3 (IFN-?3) is a newly identified cytokine with antiviral activity, and its single nucleotide polymorphisms are strongly associated with the treatment effectiveness and development of chronic hepatitis C virus infection. We thus examined the potential of IFN-?3 to inhibit HIV replication and the possible mechanisms of the anti-HIV action by IFN-?3 in human macrophages.Under different conditions (before, during, and after HIV infection), IFN-?3 significantly inhibited viral replication in macrophages, which was associated with the induction of multiple antiviral cellular factors (ISG56, MxA, OAS-1, A3G/F and tetherin) and IFN regulatory factors (IRF-1, 3, 5, 7 and 9). This anti-HIV action of IFN-?3 could be compromised by the JAK-STAT inhibitor. In addition, IFN-?3 treatment of macrophages induced the expression of toll-like receptor 3 (TLR3) and two key adaptors (MyD88 and TRIF) in type I IFN pathway activation. However, HIV infection compromised IFN-?3-mediated induction of the key elements in JAK-STAT signaling pathway.These data indicate that IFN-?3 exerts its anti-HIV function by activating JAK-STAT pathway-mediated innate immunity in macrophages. Future in vivo studies are necessary in order to explore the potential for developing IFN-?3-based therapy for HIV disease.

SUBMITTER: Liu MQ 

PROVIDER: S-EPMC3338759 | biostudies-other | 2012

REPOSITORIES: biostudies-other