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TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice
- Source :
- Cell Reports, Vol 15, Iss 8, Pp 1715-1727 (2016)
- Publisher :
- The Author(s).
-
Abstract
- Summary 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.
- Subjects :
- 0301 basic medicine
CD4-Positive T-Lymphocytes
Sexual transmission
Inflammation
HIV Infections
Cervix Uteri
Virus Replication
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
Chimera (genetics)
Mice
0302 clinical medicine
Immune system
Interferon
Gene Knockdown Techniques
Medicine
Animals
Humans
RNA, Small Interfering
lcsh:QH301-705.5
Gene knockdown
Base Sequence
business.industry
Chimera
Macrophages
HIV
Interferon-beta
Phosphoproteins
Virology
3. Good health
030104 developmental biology
Exodeoxyribonucleases
Viral replication
Gene Expression Regulation
lcsh:Biology (General)
030220 oncology & carcinogenesis
Immunology
Vagina
Female
medicine.symptom
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....b9512d2fe4283ac6d0fbf234a2b67503
- Full Text :
- https://doi.org/10.1016/j.celrep.2016.04.048