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

Sunnie M. Yoh, João I. Mamede, Derrick Lau, Narae Ahn, Maria T. Sánchez-Aparicio, Joshua Temple, Andrew Tuckwell, Nina V. Fuchs, Gianguido C. Cianci, Laura Riva, Heather Curry, Xin Yin, Stéphanie Gambut, Lacy M. Simons, Judd F. Hultquist, Renate König, Yong Xiong, Adolfo García-Sastre, Till Böcking, Thomas J. HopeSumit K. Chanda

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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 surveillance machinery 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.

Original languageEnglish
Pages (from-to)2871-2884.e6
JournalMolecular Cell
Volume82
Issue number15
DOIs
StatePublished - 4 Aug 2022

Keywords

  • HIV-1 capsid
  • PQBP1
  • cGAS
  • innate sensing
  • two-factor authentication
  • uncoating

Fingerprint

Dive into the research topics of 'Recognition of HIV-1 capsid by PQBP1 licenses an innate immune sensing of nascent HIV-1 DNA'. Together they form a unique fingerprint.

Cite this