文摘
There are twelve human interferon alpha subtypes that differentially trigger intrinsic, innate, and adaptive immune responses to viral infections. IFN伪2 is currently in HIV clinical trials, but the other subtypes have not been tested and may be better HIV therapeutics. We used HIV-1-infected humanized mice to compare the antiviral properties of IFN伪2 with IFN伪14, the subtype we found to induce the most potent anti-HIV effect in vitro. After ten days of post-exposure prophylaxis, IFN伪14 suppressed virus much better than IFN伪2 with no detectable plasma HIV p24 and greatly reduced or undetectable plasma RNA and provirus levels. Furthermore, CXCL10, an inflammatory chemokine indicative of pathological immune activation, was elevated in IFN伪2-treated but not IFN伪14-treated animals. IFN伪14 efficacy was associated with up-regulated BST2 (tetherin) and MX2 transcripts and TRAIL expression on NK cells but no significant activation of adaptive immune responses. Treatment of chronically HIV-1-infected humanized mice with IFN伪14 resulted in significant decrease in plasma HIV p24 and plasma RNA levels. IFN伪14 strongly outperformed IFN伪2 as an HIV anti-viral in humanized mice.