Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys.

TitleRapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys.
Publication TypeJournal Article
Year of Publication2016
AuthorsBarouch DH, Ghneim K, Bosche WJ, Li Y, Berkemeier B, Hull M, Bhattacharyya S, Cameron M, Liu J, Smith K, Borducchi E, Cabral C, Peter L, Brinkman A, Shetty M, Li H, Gittens C, Baker C, Wagner W, Lewis MG, Colantonio A, Kang H-J, Li W, Lifson JD, Piatak M, Sekaly R-P
JournalCell
Volume165
Issue3
Pagination656-67
Date Published2016 Apr 21
ISSN1097-4172
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-β 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.

DOI10.1016/j.cell.2016.03.021
Alternate JournalCell
PubMed ID27085913
PubMed Central IDPMC4842119
Grant ListU19 AI078526 / AI / NIAID NIH HHS / United States
U19 AI095985 / AI / NIAID NIH HHS / United States
U19 AI096040 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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