A Novel Phenotype Links HIV-1 Capsid Stability to cGAS-Mediated DNA Sensing-Reference-Cited by-同舟云学术

A Novel Phenotype Links HIV-1 Capsid Stability to cGAS-Mediated DNA Sensing

Published:2019-08-15 Issue:16 Volume:93 Page:
ISSN:0022-538X
Container-title:Journal of Virology
language:en
Short-container-title:J Virol

Author:

Siddiqui Mohammad Adnan¹,Saito Akatsuki¹^ORCID,Halambage Upul D.²,Ferhadian Damien¹,Fischer Douglas K.³,Francis Ashwanth C.⁴,Melikyan Gregory B.⁴⁵,Ambrose Zandrea³^ORCID,Aiken Christopher²,Yamashita Masahiro¹^ORCID

Affiliation:

1. Aaron Diamond AIDS Research Center, New York, New York, USA

2. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

3. Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

4. Department of Pediatrics, Emory University, Atlanta, Georgia, USA

5. Children's Healthcare of Atlanta, Atlanta, Georgia, USA

Abstract

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.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of General Medical Sciences

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Link

https://journals.asm.org/doi/pdf/10.1128/JVI.00706-19

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