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Binding of the pathogen receptor HSP90AA1 to avibirnavirus VP2 induces autophagy by inactivating the AKT-MTOR pathway.
Hu, Boli; Zhang, Yina; Jia, Lu; Wu, Huansheng; Fan, Chengfei; Sun, Yanting; Ye, Chengjin; Liao, Min; Zhou, Jiyong.
Afiliação
  • Hu B; a Key Laboratory of Animal Virology of Ministry of Agriculture ; Zhejiang University ; Hangzhou , China.
Autophagy ; 11(3): 503-15, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25714412
ABSTRACT
Autophagy is an essential component of host innate and adaptive immunity. Viruses have developed diverse strategies for evading or utilizing autophagy for survival. The response of the autophagy pathways to virus invasion is poorly documented. Here, we report on the induction of autophagy initiated by the pathogen receptor HSP90AA1 (heat shock protein 90 kDa α [cytosolic], class A member 1) via the AKT-MTOR (mechanistic target of rapamycin)-dependent pathway. Transmission electron microscopy and confocal microscopy revealed that intracellular autolysosomes packaged avibirnavirus particles. Autophagy detection showed that early avibirnavirus infection not only increased the amount of light chain 3 (LC3)-II, but also upregulated AKT-MTOR dephosphorylation. HSP90AA1-AKT-MTOR knockdown by RNA interference resulted in inhibition of autophagy during avibirnavirus infection. Virus titer assays further verified that autophagy inhibition, but not induction, enhanced avibirnavirus replication. Subsequently, we found that HSP90AA1 binding to the viral protein VP2 resulted in induction of autophagy and AKT-MTOR pathway inactivation. Collectively, our findings suggest that the cell surface protein HSP90AA1, an avibirnavirus-binding receptor, induces autophagy through the HSP90AA1-AKT-MTOR pathway in early infection. We reveal that upon viral recognition, a direct connection between HSP90AA1 and the AKT-MTOR pathway trigger autophagy, a critical step for controlling infection.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Autofagia / Proteínas de Choque Térmico HSP90 / Avibirnavirus / Proteínas do Capsídeo / Proteínas Proto-Oncogênicas c-akt / Serina-Treonina Quinases TOR Limite: Animais / Humanos Idioma: Inglês Revista: Autophagy Ano de publicação: 2015 Tipo de documento: Artigo País de afiliação: China