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- W2983603645 abstract "Summary 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 is not a strong inducer of IFN we have hypothesised that its capsid 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 TRIM5α. Importantly, unlike wild-type HIV-1, infection with cleavage defective HIV-1 triggered an IFN response in THP-1 cells and primary human macrophages that was dependent on viral DNA and cGAS. Infection in the presence of the capsid destabilising small molecule PF-74 also induced a cGAS-dependent IFN response. These data demonstrate a protective role for capsid and suggest that antiviral activity of capsid- and protease-targeting antivirals may benefit from enhanced innate and adaptive immunity in vivo ." @default.
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- W2983603645 date "2019-11-11" @default.
- W2983603645 modified "2023-09-26" @default.
- W2983603645 title "Disrupting HIV-1 capsid formation causes cGAS sensing of viral DNA" @default.
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- W2983603645 doi "https://doi.org/10.1101/838011" @default.
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