Introduction
Porcine
epidemic diarrhea (PED) is an acute and highly contagious intestinal
infectious disease mainly caused by porcine epidemic diarrhea virus
(PEDV) (OV, 2009). This disease can cause morbidity in pigs of all ages,
with the most harmful to piglets. Clinically, it is characterized by
vomiting, diarrhea and dehydration of piglets, with a mortality rate
even reaching to 100% (XL, LY, & J, 2007). During the period of 2013
to 2015 when the rapid spread and great epidemic of PEDV occurred, the
U.S. pig industry suffered serious economic losses, with a loss of
nearly 7 million pigs (A. M & G, 2019). Similarly, the largest pig
raising country China also has long time been persecuted by this virus.
A epidemiological investigation conducted in the period of Feb, 2011 to
Mar, 2014 indicated the presence of PEDV epidemics in 29 provinces, with
the PEDV-positive rates of 61.10%–78.49% and 71.43%–83.47% in
collected samples and in surveyed pig farms, respectively (Wang D, L, &
S, 2016).
As a member of the Nidovirales order and Coronaviridae family, PEDV has
a typically corolla-shaped, mostly spherical morphology, with a diameter
ranging from 95 to 190 nm (including spikes) and an average of 130 nm,
as similar to those of other members of the coronavirus family. This
enveloped virus has a single-stranded, positive-sense RNA genome of 28
kb with a 5’ cap and a 3’-polyadenylated tail. The DNA sequences located
at the 3’ side of PEDV genome encodes 4 structural proteins, namely the
spike protein (S, 150-220 kDa), membrane protein (M, 20-30 kDa), envelop
protein (E, 7 kDa), and nucleocapsid protein (N, 58 kDa) (K. R, A, M, &
K, 2001).
PEDV-caused diarrhea firstly broke out in England in 1971, with the
clinical symptoms resembling transmissible gastroenteritis virus (TGEV).
It was firstly reported in Asia in 1982 and has thereafter had a growing
economic impact on pig farming in this region as well. Especially, China
has witnessed a rapid increase of the PED incidence in pig population
since 2010. PEDV has only one serotype, while it can still be divided
into genotype 1 (G1a and G1b) and 2 (G2a and G2b) based on the amino
acid differences in the N-terminal domain of the S gene (K. R et al.,
2001). Several large outbreaks of this disease have occurred in Asia,
with a higher mortality rate in suckling piglets than previously
described in this area, which was dominated by the G2b isolates of PEDV
2010 later. According to the epidemiological survey conducted by Li et
al in 2011, more severe PEDV infection had occurred in immunized pig
farms in China, suggesting the emergence of highly pathogenic PEDV
strains. Furthermore, the S genes of PEDV from isolated strains in China
had large variations compared with these of the vaccine strains, as
mainly reflected by the presence of mutations in the core region of
neutralization epitope (COE) in these newly emerging and highly virulent
PEDV strains . For instance, compared to the vaccine strain CV777, 5
strains of PEDV with high virulence detected in Gansu province of China
have 8 mutations in the COE (A517S, S523G, V527I, T549S, G594S, A605E,
L612F and I635V) (MZ et al., 2016). Likewise, 10 PEDV strains, including
one classical strain GDS03 isolated in Guangdong province, China from
2011 to 2013, show different mutations in the COE, with larger sequence
diversity as well (J, C, L, Y, & Y, 2014). The results of genetic
evolution analysis revealed a separate branch of them, suggesting the
prevalence of variant strains in this country (L. W et al., 2012).
Furthermore, PED still remains one of the most serious diseases of swine
especially in winter, mainly because of the failure of effectively
prevention and control. Due to strict biosecurity measures and feeding,
the prevalence of PEDV in North America exhibited a declined trend,
while the outbreaks of PEDV in Asia presented highly complex variability
as a result of the continuous occurrence and emergence of recombination
or new isolates in recent years (S. Y et al., 2019).
Similar to those of other coronaviruses (SR & S, 2005),
the infection or replication
processes of PEDV consist of several main steps, such as virus
attachment and entry, viral replication enzyme translation, genome
transcription and replication, structural protein translation, and
virion assembly and release. Besides viral proteins, many host factors
are required for these processes, which are mainly mediated by an
interacting way. Therefore,
understanding these viral proteins
and host factors as well as their
interactions not only facilitates the elucidation of the pathogenic
mechanisms of PEDV, but also benefits the development of drugs or
vaccines against this virus. In
this review, we firstly characterize these viral proteins and host
factors documented in the literatures, then discuss those cellular
events or signaling pathways involved and the interactions among them,
finally highlight the directions for future efforts.
The viral proteins
involved in PEDV infection