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Basic Characteristics of Mutations
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Mutation Site
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D185E |
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Mutation Site Sentence
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We conclude that viral DNA is the active PAMP and this notion was also supported by the observation that mutation D185E in the RT active site (HIV-1 CA-SP1 RT D185E) also reduced activation of IFIT-1 luc expression (Fig 3E) and CXCL10 secretion (Fig 3F) on infection of the THP-1 IFIT-1 reporter cells. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RT |
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Standardized Encoding Gene
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gag-pol:155348
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Genotype/Subtype
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HIV-1 |
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Viral Reference
|
-
|
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Functional Impact and Mechanisms
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|
Disease
|
HIV Infections
|
|
Immune
|
- |
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Target Gene
|
-
|
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
|
- |
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Location
|
- |
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Literature Information
|
|
PMID
|
32852081
|
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Title
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Disrupting HIV-1 capsid formation causes cGAS sensing of viral DNA
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Author
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Sumner RP,Harrison L,Touizer E,Peacock TP,Spencer M,Zuliani-Alvarez L,Towers GJ
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Journal
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The EMBO journal
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Journal Info
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2020 Oct 15;39(20):e103958
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Abstract
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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 TRIM5alpha. 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 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.
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Sequence Data
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-
|