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

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1715-1727
Number of pages13
JournalCell Reports
Volume15
Issue number8
DOIs
Publication statusPublished - May 24 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice'. Together they form a unique fingerprint.

  • Cite this

    Wheeler, L. A., Trifonova, R. T., Vrbanac, V., Barteneva, N. S., Liu, X., Bollman, B., Onofrey, L., Mulik, S., Ranjbar, S., Luster, A. D., Tager, A. M., & Lieberman, J. (2016). TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice. Cell Reports, 15(8), 1715-1727. https://doi.org/10.1016/j.celrep.2016.04.048