Multi-protomics analysis identified host cellular pathways perturbed by tick-borne encephalitis virus infection.

Autor:	Sui L; Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun, China., Wang W; Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun, China.; State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, College of Basic Medical Science, Jilin University, Changchun, China., Guo X; School of Pharmaceutical Sciences, Jilin University, Changchun, China., Zhao Y; Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun, China., Tian T; State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, College of Basic Medical Science, Jilin University, Changchun, China., Zhang J; School of Pharmaceutical Sciences, Jilin University, Changchun, China., Wang H; Biomaterials and Translational Medicine, Puheng Technology Co., Ltd, Suzhou, China., Xu Y; Clinical Medical College, Changchun University of Chinese Medicine, Changchun, China., Chi H; Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun, China., Xie H; State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, College of Basic Medical Science, Jilin University, Changchun, China., Xu W; Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun, China., Liu N; Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun, China., Zhao L; Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun, China., Song G; Biomaterials and Translational Medicine, Puheng Technology Co., Ltd, Suzhou, China., Wang Z; Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun, China., Zhang K; Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun, China., Che L; Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun, China., Zhao Y; Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun, China. yichengzhao@live.cn.; Clinical Medical College, Changchun University of Chinese Medicine, Changchun, China. yichengzhao@live.cn.; China-Japan Union Hospital of Jilin University, Changchun, China. yichengzhao@live.cn., Wang G; State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, College of Basic Medical Science, Jilin University, Changchun, China. qing@jlu.edu.cn., Liu Q; Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun, China. liuquan1973@hotmail.com.; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China. liuquan1973@hotmail.com.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2024 Nov 30; Vol. 15 (1), pp. 10435. Date of Electronic Publication: 2024 Nov 30.
DOI:	10.1038/s41467-024-54628-w
Abstrakt:	Tick-borne encephalitis virus (TBEV) represents a pivotal tick-transmitted flavivirus responsible for severe neurological consequences in Europe and Asia. The emergence of TBEV genetic mutations and vaccine-breakthrough infections, along with the absence of effective vaccines and specific drugs for other tick-borne flaviviruses associated with severe encephalitis or hemorrhagic fever, underscores the urgent need for progress in understanding the pathogenesis and intervention strategies for TBEV and related flaviviruses. Here we elucidate cellular alterations in the proteome, phosphoproteome, and acetylproteome upon TBEV infection. Our findings reveal a substantial impact of TBEV infection on the innate immune response, ribosomal biogenesis, autophagy, and DNA damage response (DDR). Mechanically, the non-structural protein NS5 of TBEV impedes DNA damage repair by interacting with SIRT1 to suppress the deacetylation of KAP1 and Ku70. Additionally, the precursor membrane protein prM induces autophagy via associating with AKT1 while constrains autolysosome formation through binding to VPS11. Inhibitors targeting DDR, as well as specific kinases, exhibit potent antiviral activity, suggesting the dysregulated pathways and kinases as potential targets for antiviral intervention. These results from our study contribute to elucidating the pathogenesis and offers insights for developing effective antiviral drugs against TBEV and other tick-borne flaviviruses. Competing Interests: Competing interests: The authors declare no conflicts of interest. (© 2024. The Author(s).)
Databáze:	MEDLINE
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