Viral tegument proteins restrict cGAS-DNA phase separation to mediate immune evasion
| Autor: | Panpan Sun, Han Feng, Yina Gao, Songqing Liu, Sheng Zhou, Shu Zhu, Xiu Luo, Hongyu Deng, Jingpeng Zhu, Chong Liu, Quanjin Li, Dong Li, Qi Zhan, Yun Feng, Guangjun Xu, Pu Gao |
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| Rok vydání: | 2021 |
| Předmět: |
Protein family
Viral protein Host–pathogen interaction Biology Alphaherpesvirinae medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system medicine Betaherpesvirinae Humans Molecular Biology Pathogen 030304 developmental biology Immune Evasion Viral Structural Proteins 0303 health sciences Innate immune system Cell Biology Viral tegument DNA Herpesviridae Infections Nucleotidyltransferases Immunity Innate Cell biology HEK293 Cells chemistry 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | Molecular cell. 81(13) |
| ISSN: | 1097-4164 |
| Popis: | Summary DNA-induced liquid-liquid phase separation of cyclic GMP-AMP synthase (cGAS) triggers a potent response to detect pathogen infection and promote innate immune signaling. Whether and how pathogens manipulate cGAS-DNA condensation to mediate immune evasion is unknown. We report the identification of a structurally related viral tegument protein family, represented by ORF52 and VP22 from gamma- and alpha-herpesvirinae, respectively, that employs a conserved mechanism to restrict cGAS-DNA phase separation. ORF52/VP22 proteins accumulate into, and effectively disrupt, the pre-formed cGAS-DNA condensation both in vitro and in cells. The inhibition process is dependent on DNA-induced liquid-liquid phase separation of the viral protein rather than a direct interaction with cGAS. Moreover, highly abundant ORF52 proteins carried within viral particles are able to target cGAS-DNA phase separation in early infection stage. Our results define ORF52/VP22-type tegument proteins as a family of inhibitors targeting cGAS-DNA phase separation and demonstrate a mechanism for how viruses overcome innate immunity. |
| Databáze: | OpenAIRE |
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