Id |
Subject |
Object |
Predicate |
Lexical cue |
T11 |
0-2 |
Sentence |
denotes |
1. |
T12 |
3-15 |
Sentence |
denotes |
Introduction |
T13 |
16-157 |
Sentence |
denotes |
Porcine epidemic diarrhea virus (PEDV) is an enveloped, positive-sense and single stranded RNA virus belonging to the genus Alphacoronavirus. |
T14 |
158-367 |
Sentence |
denotes |
PEDV is the causative agent of porcine epidemic diarrhea (PED), a historic, highly contagious enteric swine disease characterized by diarrhea, dehydration and poor growth performance in pigs at all ages [1,2]. |
T15 |
368-564 |
Sentence |
denotes |
PED was first identified in 1971 in the United Kingdom, and subsequently became an endemic disease in the Europe and most Asian countries with a low mortality rate and limited economic losses [1]. |
T16 |
565-705 |
Sentence |
denotes |
For decades, the disease was controlled through the use of live attenuated vaccines (LAVs) derived from the PEDV prototypes, CV777- or DR13. |
T17 |
706-839 |
Sentence |
denotes |
Unfortunately, in late 2010, a new highly virulent PEDV strain emerged in China and quickly spread worldwide, including Taiwan [3,4]. |
T18 |
840-1100 |
Sentence |
denotes |
Moreover, the conventional LAV failed to induce protection against this new virulent PEDV strain, consequently resulting in nearly 100% mortality amongst neonatal piglets and leading to substantial economic impacts on swine markets in the affected regions [5]. |
T19 |
1101-1164 |
Sentence |
denotes |
Phylogenetic analysis categorizes PEDV into two genogroups [2]. |
T20 |
1165-1362 |
Sentence |
denotes |
Genogroup I consists primarily of the historic, low-virulent PEDV strains that appeared around 1970, whereas genogroup II is composed of the highly virulent PEDV strains, which emerged after 2010s. |
T21 |
1363-1570 |
Sentence |
denotes |
Both genogroups can be further divided into two subgroups each, namely G1a, G1b, G2a and G2b though a recent phylogenetic study identified a novel recombinant PEDV strain classified into a new G1c clade [6]. |
T22 |
1571-1682 |
Sentence |
denotes |
The complete genome of PEDV is approximately 28 kilobase pairs and consists of seven open reading frames (ORF). |
T23 |
1683-1955 |
Sentence |
denotes |
Out of the seven, four ORFs are responsible for encoding structural proteins, namely the spike (S) glycoprotein as well as envelop (E), membrane (M), and nucleocapsid (N) proteins, which are crucial for viral morphogenesis and establishment of infection establishment [7]. |
T24 |
1956-2133 |
Sentence |
denotes |
Among all coronaviruses, S glycoprotein plays a particularly essential role in cell-virus interaction and acts as the vital determinants of viral virulence/attenuation [8,9,10]. |
T25 |
2134-2275 |
Sentence |
denotes |
S glycoprotein is a homotrimeric type I fusion protein, which can be cleaved into two parts—the S1 and S2 subunits—by cellular protease [11]. |
T26 |
2276-2482 |
Sentence |
denotes |
The S1 subunit contains the receptor binding domain (RBD) and several neutralizing epitopes that are essential for determining host and tissue tropism, and triggering protective host immunity, respectively. |
T27 |
2483-2583 |
Sentence |
denotes |
Therefore, the S1 subunit has long been considered to be the primary target for vaccine development. |
T28 |
2584-2725 |
Sentence |
denotes |
The S2 domain, on the other hand, mediates membrane fusion which facilitates release of viral RNA and infection to the neighboring cells [8]. |
T29 |
2726-2834 |
Sentence |
denotes |
LAVs have been shown to be the most effective way to elicit protective immunity against PEDV infection [12]. |
T30 |
2835-3011 |
Sentence |
denotes |
Therefore, to combat the emergence of PED as well as to immediately suppress any future outbreaks, studies have been carried out to develop safe and effective vaccines [13,14]. |
T31 |
3012-3267 |
Sentence |
denotes |
Aside from serial cell culture or animal passages, the reverse genetic system, which rescues genetically modified attenuated viruses, is now the common approach in generating LAV candidates for both human and animal viral diseases, including PEDV [15,16]. |
T32 |
3268-3441 |
Sentence |
denotes |
To this end, understanding the molecular biology and identification of virulent/attenuating determinant(s) are necessary for the rational design of potential LAV candidates. |
T33 |
3442-3665 |
Sentence |
denotes |
Comparison of the genomic differences between the Vero cell-cultured attenuated G2b PEDV and their corresponding parental virulent strains has revealed a common pattern of mutation that particularly affects the S gene [12]. |
T34 |
3666-3971 |
Sentence |
denotes |
While the observation is reasonable considering the fundamental role of S protein in PEDV infection and induction of host immunity, a recent publication found that a singular S gene exchange had no influence on the virulence of the highly virulent G2b BJ2011C strain and avirulent G1a CHM2013 strain [17]. |
T35 |
3972-4208 |
Sentence |
denotes |
In the present study, we utilized reverse genetics to examine the role of the S gene in the attenuation process of PEDV using the highly virulent and attenuated G2b PEDV Pintung (PEDVPT) 52 strains, the PEDVPT-P5 and PEDVPT-P96 viruses. |
T36 |
4209-4284 |
Sentence |
denotes |
Nonetheless, our findings were discordant with previous reported data [17]. |
T37 |
4285-4395 |
Sentence |
denotes |
We found that replacement of the S gene with the iPEDVPT-P5 virus enabled iPEDVPT-P96 to regain its virulence. |
T38 |
4396-4520 |
Sentence |
denotes |
A reciprocal approach revealed that iPEDVPT-P5 virus became partly attenuated after the S gene was exchanged to iPEDVPT-P96. |
T39 |
4521-4641 |
Sentence |
denotes |
Collectively, we concluded that the S gene is of critical importance to the attenuation process of the PEDVPT 52 strain. |
T40 |
4642-4732 |
Sentence |
denotes |
However, mutation in the S gene alone could not completely attenuate the iPEDVPT-P5 virus. |
T41 |
4733-4817 |
Sentence |
denotes |
Thus, gene(s) other than S gene could also play a role in determining the virulence. |