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

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• 作者：Kathrin Gibbert¹ ; ; Kerry J. Lavender² ; Karin E. Peterson² ; Jan Mü ; nch³ ; Jacob Piehler⁴ ; Mario L. Santiago⁵ ; Jens Verheyen¹ ; Kim Hasenkrug² ; Ulf Dittmer¹
• 刊名：Cytokine
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：76
• 期：1
• 页码：71-72
• 全文大小：52 K

文摘

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