Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys

被引：110

作者：

Barouch, Dan H. ^{[1
,2
]}

Ghneim, Khader ^{[3
]}

Bosche, William J. ^{[4
]}

Li, Yuan ^{[4
]}

Berkemeier, Brian ^{[4
]}

Hull, Michael ^{[4
]}

Bhattacharyya, Sanghamitra ^{[3
]}

Cameron, Mark ^{[3
]}

Liu, Jinyan ^{[1
]}

Smith, Kaitlin ^{[1
]}

Borducchi, Erica ^{[1
]}

Cabral, Crystal ^{[1
]}

Peter, Lauren ^{[1
]}

Brinkman, Amanda ^{[1
]}

Shetty, Mayuri ^{[1
]}

Li, Hualin ^{[1
]}

Gittens, Courtney ^{[5
]}

Baker, Chantelle ^{[5
]}

Wagner, Wendeline ^{[5
]}

Lewis, Mark G. ^{[5
]}

Colantonio, Arnaud ^{[6
]}

Kang, Hyung-Joo ^{[7
]}

Li, Wenjun ^{[7
]}

Lifson, Jeffrey D. ^{[4
]}

Piatak, Michael, Jr. ^{[4
]}

Sekaly, Rafick-Pierre ^{[3
]}

机构：

[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA

[2] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

[3] Case Western Reserve Univ, Cleveland, OH 44106 USA

[4] Frederick Natl Lab, AIDS & Canc Virus Program, Leidos Biomed Res, Frederick, MD 21702 USA

[5] Bioqual, Rockville, MD 20852 USA

[6] New England Reg Primate Res Ctr, Southborough, MA 01772 USA

[7] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA

来源：

CELL | 2016年 / 165卷 / 03期

关键词：

SIMIAN IMMUNODEFICIENCY VIRUS; CD4(+) T-CELLS; PREDICTING GENE-FUNCTION; RESPONSES; TRANSMISSION; DISEASE; NLRX1; HIV; REPLICATION; PROPAGATION;

D O I：

10.1016/j.cell.2016.03.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：656 / 667

页数：12

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