University of Massachusetts Medical School Faculty Publications

Title

Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys

UMMS Affiliation

Department of Medicine, Division of Preventive and Behavioral Medicine; Department of Medicine, Division of Cardiovascular Medicine

Date

4-21-2016

Document Type

Article

Disciplines

Immunology and Infectious Disease

Abstract

The earliest events following mucosal HIV-1 infection, prior to measurable viremia, remain poorly understood. Here, by detailed necropsy studies, we show that the virus can rapidly disseminate following mucosal SIV infection of rhesus monkeys and trigger components of the inflammasome, both at the site of inoculation and at early sites of distal virus spread. By 24 hr following inoculation, a proinflammatory signature that lacked antiviral restriction factors was observed in viral RNA-positive tissues. The early innate response included expression of NLRX1, which inhibits antiviral responses, and activation of the TGF-beta pathway, which negatively regulates adaptive immune responses. These data suggest a model in which the virus triggers specific host mechanisms that suppress the generation of antiviral innate and adaptive immune responses in the first few days of infection, thus facilitating its own replication. These findings have important implications for the development of vaccines and other strategies to prevent infection.

Rights and Permissions

Citation: Cell. 2016 Apr 21;165(3):656-67. doi: 10.1016/j.cell.2016.03.021. Epub 2016 Apr 13. Link to article on publisher's site

Comments

Full author list omitted for brevity. For full list of authors see article.

Related Resources

Link to Article in PubMed

PubMed ID

27085913