Abstract
Type III interferons (IFN-λs) have been demonstrated to inhibit a number of viruses, including HIV. Here, we further examined the anti-HIV effect of IFN-λs in macrophages. We found that IFN-λs synergistically enhanced anti-HIV activity of antiretrovirals [azidothymidine (AZT), efavirenz, indinavir, and enfuvirtide] in infected macrophages. Importantly, IFN-λs could suppress HIV infection of macrophages with the drug-resistant strains, including AZT-resistant virus (A012) and reverse transcriptase inhibitor-resistant virus (TC49). Mechanistically, IFN-λs were able to induce the expression of several important anti-HIV cellular factors, including myxovirus resistance 2 (Mx2), a newly identified HIV post-entry inhibitor and tetherin, a restriction factor that blocks HIV release from infected cells. These observations provide additional evidence to support the potential use of IFN-λs as therapeutics agents for the treatment of HIV infection.
Highlights
Active antiretroviral therapy (HAART) has substantially reduced morbidity and mortality in HIV-infected individuals since its introduction in 1996 [1]
We examined whether IFN-λs (1, 2, or 3) can inhibit drugresistant HIV infection of macrophages
IFN-λs bind to their own distinctive receptor complex, IL-10Rβ and IL-28Rα, which activates janus kinase/signal transducers and activators of the transcription (JAK/STAT) signaling pathway, resulting in the phosphorylation of STAT proteins and forming of IFN-stimulated gene factor 3 complex [11, 15, 52]
Summary
Active antiretroviral therapy (HAART) has substantially reduced morbidity and mortality in HIV-infected individuals since its introduction in 1996 [1]. HAART can suppress plasma viral loads to undetectable levels and improve patient life span [2], a substantial fraction of patients fail therapy and/or experience serious side effects from treatment, accompanied by the emergence of drug-resistant viruses [3, 4]. It is known that macrophages play a crucial role in the host defense against HIV-1 infection, as they produce the multiple intracellular HIV restriction factors [7, 8]. As HIV-1 latency is the major obstacle in preventing the eradication of the virus, it is necessary to identify agents that can induce intracellular antiviral factors against HIV-1 in macrophages
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
