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

文献类型： 外文期刊

第一作者： Yoh, Sunnie M.

作者： Yoh, Sunnie M.;Ahn, Narae;Curry, Heather;Chanda, Sumit K.;Mamede, Joao, I;Cianci, Gianguido C.;Hope, Thomas J.;Lau, Derrick;Tuckwell, Andrew;Bocking, Till;Sanchez-Aparicio, Maria T.;Garcia-Sastre, Adolfo;Temple, Joshua;Xiong, Yong;Fuchs, Nina, V;Koenig, Renate;Mamede, Joao, I;Gambut, Stephanie;Sanchez-Aparicio, Maria T.;Garcia-Sastre, Adolfo;Garcia-Sastre, Adolfo;Riva, Laura;Yin, Xin;Simons, Lacy M.;Hultquist, Judd F.;Simons, Lacy M.;Hultquist, Judd F.;Garcia-Sastre, Adolfo

作者机构：

期刊名称：MOLECULAR CELL （ 影响因子：19.328； 五年影响因子：20.747 ）

ISSN： 1097-2765

年卷期： 2022 年 82 卷 15 期

页码：

收录情况： SCI

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.

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