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

Publication date: Available online 12 May 2016 Source:Cell Reports Author(s): Lee Adam Wheeler, Radiana T. Trifonova, Vladimir Vrbanac, Natasha S. Barteneva, Xing Liu, Brooke Bollman, Lauren Onofrey, Sachin Mulik, Shahin Ranjbar, Andrew D. Luster, Andrew M. Tager, Judy Lieberman 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. Graphical abstract Teaser Wheeler et al. describe the effect of knocking down TREX1 on genital HIV tran...

Source: Cell Reports - May 12, 2016 Category: Cytology Source Type: research