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