Recognition of HIV-1 capsid by PQBP1 licenses an innate immune sensing of nascent HIV-1 DNA

被引：32

作者：

Yoh, Sunnie M. ^{[1
]}

Mamede, Joao, I ^{[2
,7
]}

Lau, Derrick ^{[3
]}

Ahn, Narae ^{[1
]}

Sanchez-Aparicio, Maria T. ^{[4
,8
]}

Temple, Joshua ^{[5
]}

Tuckwell, Andrew ^{[3
]}

Fuchs, Nina, V ^{[6
]}

Cianci, Gianguido C. ^{[2
]}

Riva, Laura ^{[10
]}

Curry, Heather ^{[1
]}

Yin, Xin ^{[11
]}

Gambut, Stephanie ^{[7
]}

Simons, Lacy M. ^{[12
,13
]}

Hultquist, Judd F. ^{[12
,13
]}

Koenig, Renate ^{[6
]}

Xiong, Yong ^{[5
]}

Garcia-Sastre, Adolfo ^{[4
,8
,9
,14
]}

Bocking, Till ^{[3
]}

Hope, Thomas J. ^{[2
]}

Chanda, Sumit K. ^{[1
]}

机构：

[1] Scripps Res, Dept Immunol & Microbiol, La Jolla, CA 92037 USA

[2] Northwestern Univ, Dept Cell & Dev Biol, Feinberg Sch Med, Chicago, IL 60612 USA

[3] Univ New South Wales, Sch Med Sci, EMBL Australia Node Single Mol Sci, Sydney, NSW, Australia

[4] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[5] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06511 USA

[6] Paul Ehrlich Inst, Host Pathogen Interact, D-63225 Langen, Germany

[7] Rush Univ, Dept Microbial Pathogens & Immun, Med Ctr, Chicago, IL 60612 USA

[8] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA

[9] Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, New York, NY 10029 USA

[10] Calibr, La Jolla, CA 92037 USA

[11] Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Vet Biotechnol, Harbin 150069, Peoples R China

[12] Northwestern Univ, Dept Med, Div Infect Dis, Feinberg Sch Med, Chicago, IL 60611 USA

[13] Northwestern Univ, Ctr Pathogen Genom & Microbial Evolut, Inst Global Hlth, Feinberg Sch Med, Chicago, IL 60611 USA

[14] Icahn Sch Med Mt Sinai, Dept Pathol Mol & Cell Based Med, New York, NY 10029 USA

来源：

MOLECULAR CELL | 2022年 / 82卷 / 15期

基金：

美国国家卫生研究院;

关键词：

GMP-AMP SYNTHASE; RIBONUCLEASE H; SENSOR; INFECTION; IDENTIFICATION; INHIBITORS; MUTATIONS; REVEAL; DOMAIN; SITES;

D O I：

10.1016/j.molcel.2022.06.010

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：

We have previously described polyglutamine-binding protein 1 (PQBP1) as an adapter required for the cyclic GMP-AMP synthase (cGAS)-mediated innate response to the human immunodeficiency virus 1 (HIV-1) and other lentiviruses. Cytoplasmic HIV-1 DNA is a transient and low-abundance pathogen-associated molecular pattern (PAMP), and the mechanism for its detection and verification is not fully understood. Here, we show a two-factor authentication strategy by the innate surveillancemachinery to selectively respond to the low concentration of HIV-1 DNA, while distinguishing these species from extranuclear DNA molecules. We find that, upon HIV-1 infection, PQBP1 decorates the intact viral capsid, and this serves as a primary verification step for the viral nucleic acid cargo. As reverse transcription and capsid disassembly initiate, cGAS is recruited to the capsid in a PQBP1-dependent manner. This positions cGAS at the site of PAMP generation and sanctions its response to a low-abundance DNA PAMP.

引用

页码：2871 / +

页数：20

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