PARP-1 mediated cell death is directly activated by ZIKV infection.

Autor: Xu G; Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, 518112, China. Electronic address: xugang2513@sina.com., Li S; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China., Liu X; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China., Gao P; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China., Chen X; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China., Wang H; Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, 518112, China., Zhang M; Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, 518112, China., Yang Y; Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, 518112, China., Gao GF; Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, 518112, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China., Zhang F; Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, 518112, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China. Electronic address: zhangfp@im.ac.cn.
Jazyk: angličtina
Zdroj: Virology [Virology] 2019 Nov; Vol. 537, pp. 254-262. Date of Electronic Publication: 2019 Aug 25.
DOI: 10.1016/j.virol.2019.08.024
Abstrakt: Zika virus (ZIKV) has emerged as a severe health threat due to its association with microcephaly. It has been reported that the strong cytopathic effects, including cell-cycle arrest and cell death are responsible for the nervous system disease. However, the mechanisms by which ZIKV infection induced cell death were largely unknown. Here, we reported that cell death is readily detected after ZIKV infection as indicated by PI staining and the reduction of cell viability. Importantly, cell death can be induced by overexpression of ZIKV NS3 protein alone but not the other non-structure proteins. Mass spectrometry analysis revealed that NS3 bond to and activated PARP-1. In agreement with these observations, we found that PARP-1 was massively activated during ZIKV infection and the intracellular ATP and NAD + concentrations rapidly declined. Finally, PARP-1 knockdown simultaneously restrained ZIKV infection-induced cell death and ablated host restriction of virus infection. Our finding indicates that PARP-1 activation is an important cellular event during ZIKV infection, which contributes to the cell death.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE