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).