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TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice

2016; Cell Press; Volume: 15; Issue: 8 Linguagem: Inglês

10.1016/j.celrep.2016.04.048

2639-1856

Lee Adam Wheeler, Radiana Trifonova, Vladimir Vrbanac, Natasha S. Barteneva, Xing Liu, Brooke Bollman, Lauren Onofrey, Sachin Mulik, Shahin Ranjbar, Andrew D. Luster, Andrew M. Tager, Judy Lieberman,

Herpesvirus Infections and Treatments

Despite their antiviral effect, the in vivo effect of interferons on HIV transmission is difficult to predict, because interferons also activate and recruit HIV-susceptible cells to sites of infection. HIV does not normally induce type I interferons in infected cells, but does if TREX1 is knocked down. Here, we investigated the effect of topical TREX1 knockdown and local interferon production on HIV transmission in human cervicovaginal explants and humanized mice. In explants in which TREX1 was knocked down, HIV induced interferons, which blocked infection. In humanized mice, even though TREX1 knockdown increased infiltrating immune cells, it delayed viral replication for 3–4 weeks. Similarly intravaginal application of type I interferons the day before HIV infection induced interferon responsive genes, reduced inflammation, and decreased viral replication. However, intravenous interferon enhanced inflammation and infection. Thus, in models of human sexual transmission, a localized interferon response inhibits HIV transmission but systemic interferons do not.