ID: 41: Treatment with interferon alpha subtype 14 potently suppresses HIV infection in humanized mice

Abstract

There are twelve human interferon alpha subtypes that differentially trigger intrinsic, innate, and adaptive immune responses to viral infections. IFN α 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 α 2 with IFN α 14, the subtype we found to induce the most potent anti-HIV effect in vitro. After ten days of post-exposure prophylaxis, IFN α 14 suppressed virus much better than IFN α 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 α 2-treated but not IFN α 14-treated animals. IFN α 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 α 14 resulted in significant decrease in plasma HIV p24 and plasma RNA levels. IFN α 14 strongly outperformed IFN α 2 as an HIV anti-viral in humanized mice.