Disrupting HIV-1 capsid formation causes cGAS sensing of viral DNA

ABSTRACT: Detection of viral DNA by cyclic GMP-AMP synthase (cGAS) is a first line of defence leading to the production of type-I interferon (IFN). As HIV-1 replication is not a strong inducer of IFN we hypothesised that an intact capsid physically cloaks viral DNA from cGAS. To test this we generated defective viral particles by treatment with HIV-1 protease inhibitors or by genetic manipulation of gag. These viruses had defective Gag cleavage, reduced infectivity and diminished capacity to saturate TRIM5?. Importantly, unlike wild-type HIV-1, infection with cleavage defective HIV-1 triggered an IFN response in THP-1 cells that was dependent on viral DNA and cGAS. An IFN response was also observed in primary human macrophages infected with cleavage defective viruses. Infection in the presence of th

SUBMITTER: Dr. Rebecca, P Sumner 

PROVIDER: S-SCDT-EMBOJ-2019-103958 | biostudies-other |

REPOSITORIES: biostudies-other