The dual regulation of apoptosis by Flavivirus
Running title: apoptosis regulation by Flavivirus
Yuhong Pan1,2,3, Anchun Cheng1,2,3,*, Mingshu Wang1,2,3,Zhongqiong Yin3 and Renyong Jia1,2,3,*
1 Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China;
2Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China;
3Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, 611130, China
* Corresponding authors at: Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China.
E-mail addresses:jiary@sicau.edu.cn (R. Jia),chenganchun@vip.163.com(A. Cheng)
Abstract: Apoptosis is a form of programmed cell death, which maintains cellular homeostasis by eliminating pathogen-infected cells. It contains three signaling pathways: death receptor pathway, mitochondria-mediated pathway and endoplasmic reticulum pathway. Its importance in host defenses is highlighted by the observation that many viruses evade, hinder or destroy apoptosis, thereby weakening the host’s immune response. Flaviviruses such as Dengue virus, Japanese encephalitis virus and West Nile virus utilize various strategies to activate or inhibit cell apoptosis. This article reviews the research progress of apoptosis mechanism during flaviviruses infection, including flaviviruses proteins to regulate apoptosis by interacting with host proteins, as well as various signaling pathways involved in flaviviruses-induced apoptosis, which provides a scientific basis for understanding the pathogenesis of flaviviruses and helps in developing an effective antiviral therapy.
Keywords: apoptosis; flavivirus; Dengue virus; Japanese encephalitis virus, West Nile virus; Zika virus
Flavivirus
Flavivirus belong to the Flaviviridae family and have 70 different antigen-related members. Flavivirus is an emerging arthropod-borne virus that causes huge global health problems. According to the epidemic reports, Dengue virus (DENV), Japanese Encephalitis Virus (JEV), West Nile virus (WNV), Zika virus (ZIKV), Yellow fever virus (YFV) and tick-borne Encephalitis virus (TBEV) are major human pathogenic flaviviruses(Rastogi, Sharma, & Singh, 2016). They are responsible for the illness ranging from mild flu symptoms to severe hemorrhagic, neurological and cognitive manifestations that cause death.
Structure
Flavivirus is a single-stranded, positive-polarity RNA virus with a genome of approximately 11 kb, which has only one open reading frame (ORF) flanked by a 5’-untranslated region (UTR) and a 3’-untranslated region (Figure 1). The ORF encodes a polyprotein of ~3400 aa residues, which is cleaved by viral and host protease to produce three structural proteins (capsid [C]; precursor of M [prM] and envelope [E]) and seven nonstructural (NS) proteins (NS1, NS2A/2B, NS3, NS4A/4B and NS5)(Juan Huang et al., 2018; Tao et al., 2012; Wanjun et al., 2012).