Introduction
Coronaviruses (CoVs) can infect a wide variety of animals, and cause respiratory, enteric, and other diseases (Woo et al., 2006). So far, the most relevant enteric coronaviruses in pigs include porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and recently identified viruses, such as porcine deltacoronavirus (PDCoV) and swine acute diarrhea syndrome coronavirus (SADS-CoV) (Gong et al., 2017; L. Wang, Byrum, & Zhang, 2014a). Among them, PEDV has the highest detection rate and up to 100% mortality in neonatal piglets. The acute diarrhea caused by PEDV was characterized by severe vomiting, dehydration, and watery diarrhea (D. Wang, Fang, & Xiao, 2016). Outbreaks of the disease brought huge economic losses to pig production around the world (Song & Park, 2012).
PEDV is an enveloped virus, whose genome is composed of a positive sense, non-segmented, and single-stranded RNA with a size of 28 kb. The PEDV genome encodes ORF1ab, spike (S), ORF3, envelope (E), membrane (M), and nucleoprotein (N) from 5’ to 3’ untranslated region (UTR) (Kocherhans, Bridgen, Ackermann, & Tobler, 2001). S protein is a glycoprotein peplomer located on the viral surface, and contains 1383-1386 amino acids (aa) in most strains. Despite the S protein of PEDV cannot be demarcated by a protease cleavage site, it is divided into S1 and S2 subunits based on the homology with other coronaviruses (Duarte et al., 1994; Millet & Whittaker, 2015). The receptor for PEDV is still unknown. However, S1 protein has been shown to bind to sialic acid glycans and porcine aminopeptidase N (pAPN) as a receptor binding domain to facilitate viral invasion. S2 subunit is responsible for a membrane fusion (B. X. Li, Ge, & Li, 2007; W. Li, van Kuppeveld, He, Rottier, & Bosch, 2016). S protein is also the main target for inducing neutralizing antibodies. The neutralizing epitope region COE (499–638 aa) , four neutralizing B cell epitopes S1A (435-485 aa), SS2 (748–755 aa) , SS6 (764–771 aa), and 2C10 (1368-1374 aa) have been identified on this protein (C. Y. Chang et al., 2019; S. H. Chang et al., 2002; Okda et al., 2017; Sun et al., 2008). In addition, a specific linear B-cell epitope SE16 (722-731aa) had been identified to be required for a reactivity with the mAb 2E10. The epitope SE16 was localized on the surface of PEDV S protein based on a 3D structure (Kong et al., 2020).
PEDV was first reported in the United Kingdom in 1971 (Wood, 1977). In China, PEDV was first identified and isolated in 1984. Since then, PEDV infection occurred sporadically and regionally. In 2010, a high virulence strain of PEDV appeared on pig farms in southern China, which caused up to 100 % mortality in newborn piglets, and immediately swept throughout the country (Q. Wang, Vlasova, Kenney, & Saif, 2019). The presence of variant strain in China was identified by a detection of a field CH/FJND-3/2011 strain (J. Chen et al., 2012). The AJ1102 strain isolated from a PEDV positive farm had become the prevalent variant for the time (Bi, Zeng, Xiao, Chen, & Fang, 2012).
The epidemiological survey proceeded from February 2011 to March 2014 in 29 provinces of China showed that the PEDV positive rates for samples and pig farms were 61.10%–78.49% and 71.43%–83.47%, respectively. Genetic drift could be confirmed mainly by the genetic variation of S protein as compared with Chinese commercialized vaccine strain CV777 (N. Chen et al., 2017; X. Wang et al., 2016). PEDV is mainly classified into two genotypes GI (classical) and GII (variant) on the basis of S gene (J. Chen et al., 2012). In 2013, new PEDV variants containing new insertion and deletion in S gene versus prototype strain were reported in USA (L. Wang, Byrum, & Zhang, 2014b). Subsequently, these variants, named S-INDEL-variant, were also detected and isolated in China (D. Wang et al., 2016). S-INDEL strains were associated with milder clinical signs and lower mortality in suckling pigs.
Currently, PEDV is still the main pathogen that leads to the death of piglets on pig farms in China. High morbidity, variation, and recombination of viral genomes make it hard to prevent and control the prevalence of PEDV. To better understand the prevalence and molecular characteristics of PEDV in different regions of China, 91 PEDV positive samples from 17 provinces of China were collected. The full-length S genes were sequenced and analyzed with a focus on the variation of the neutralizing epitopes, the emergence of S-INDEL strains, and potential recombinant between different strains. These data systematically describe the genetic and evolutionary characteristics of PEDV field strains in China and promote the development of novel effective vaccines .