Open AccessA Novel Phenotype Links HIV-1 Capsid Stability to cGAS-Mediated DNA Sensing
Author(s) -
Mohammad Adnan Siddiqui,
Akatsuki Saito,
Upul D. Halambage,
Damien Ferhadian,
D Fischer,
Ashwanth C. Francis,
Gregory B. Melikyan,
Zandrea Ambrose,
Christopher Aiken,
Masahiro Yamashita
Publication year - 2019
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.00706-19
Subject(s) - capsid , biology , dna , innate immune system , phenotype , virology , viral replication , microbiology and biotechnology , virus , genetics , gene , immune system
The HIV-1 capsid, which is made from individual viral capsid proteins (CA), is a target for a number of antiviral compounds, including the small-molecule inhibitor PF74. In the present study, we utilized PF74 to identify a transmitted/founder (T/F) strain that shows increased capsid stability. Interestingly, PF74-resistant variants prevented cGAS-dependent innate immune activation under a condition where the other T/F strains induced type I interferon. These observations thus reveal a new CA-specific phenotype that couples capsid stability to viral DNA recognition by cytosolic DNA sensors.
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