LitCovid-sentences  

PMC:7019868 / 23720-31530 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T165 0-2 Sentence denotes 4.
T166 3-13 Sentence denotes Discussion
T167 14-172 Sentence denotes Porcine epidemic diarrhea (PED) to date remains a colossal burden to the global swine industries owing to the lack of successful vaccine in the field [12,13].
T168 173-479 Sentence denotes Moreover, other emerging and re-emerging swine enteric coronaviruses, including porcine deltacoronavirus (PDCoV) [24], and swine acute diarrhea syndrome coronavirus (SADS-CoV) [25], further complicate the field condition by affecting diagnostic accuracy and increasing the risk of viral recombination [26].
T169 480-614 Sentence denotes Hence, there is still a pressing need to develop a safe and effective vaccine, particularly the LAV, to mount this disastrous disease.
T170 615-772 Sentence denotes The reverse genetics system is a powerful and widely used tool to study viral pathogenesis and novel LAV design by active modification of genes of interests.
T171 773-956 Sentence denotes Previous studies using reverse genetics on other coronaviruses have identified many virulent/attenuating determinants that might be shared among different genus of coronaviruses [12].
T172 957-1094 Sentence denotes Nevertheless, direct evidences of attenuation due to harboring those mutated determinant(s) in pigs are still limited in PEDV [16,23,27].
T173 1095-1419 Sentence denotes In the present study, to investigate the role of the S gene in the attenuation process of the PEDVPT 52 strain, we generated four infectious cDNA clones of G2b PEDV, including the parental virulent iPEDVPT-P5, attenuated iPEDVPT-P96, as well as two chimeric viruses (iPEDVPT-P5-96S and iPEDVPT-P96-5S) with exchanged S gene.
T174 1420-1651 Sentence denotes We found that the iPEDVPT-P96 virus fully regained the virulence after the exchange of S gene derived from the highly virulent iPEDVPT-P5 virus, showing comparable patterns of viral shedding, diarrhea and histopathological changes.
T175 1652-1871 Sentence denotes Our data confirmed that the S gene is the primary attenuating determinant of the iPEDVPT-P96 virus and the genetic backbone other than the S gene involving the attenuation of the iPEDVPT-P96 might be of less importance.
T176 1872-2051 Sentence denotes However, the iPEDVPT-P5-96S still exhibited partial virulence resulting in severer villous attenuation and higher mortality rate compared to those caused by the iPEDVPT-P96 virus.
T177 2052-2128 Sentence denotes This result supports that the virulence of PEDV might be a multigenic event.
T178 2129-2253 Sentence denotes In the present study, the first pair of cDNA clones of a virulent G2b PEDV and its derived attenuated strain were generated.
T179 2254-2493 Sentence denotes Since these two viruses were closely related to each other, this established platform would allow for easier manipulate in studying the effect of single nucleotide polymorphism for identifying potential virulent/attenuating determinate(s).
T180 2494-2627 Sentence denotes In the present study, we demonstrated that reversion of virulence or attenuation occurred after the S gene was reciprocally replaced.
T181 2628-2897 Sentence denotes However, this finding is in disagreement with previously published results by Wang et al. [17], indicating that there was an absence of virulence reversion after S gene substitution between the highly virulent G2b strain, BJ2011C, and the avirulent G1a strain, CHM2013.
T182 2898-2997 Sentence denotes There could be a few reasons for the discrepancy between our observations that of previous studies.
T183 2998-3046 Sentence denotes First, the autonomy of the viruses is different.
T184 3047-3296 Sentence denotes Viral attenuation in serial cell-culture or animal passage is a progressive process that involves a series of gene mutations and the subsequent alternated cooperative interplay between gene products and mechanisms influencing cell-virus interaction.
T185 3297-3528 Sentence denotes Although the patterns of attenuating mutation are similar among G2b PEDV strains, the asynchronous mutations between different PEDV strains could lead to loss of the cooperative or complementary function(s) for other gene products.
T186 3529-3616 Sentence denotes In the previous study, the used viral strains belonged to different genogroups [17,28].
T187 3617-3716 Sentence denotes Efficient viral assembly requires proper signaling and interaction between each structural protein.
T188 3717-4013 Sentence denotes Since the BJ2011C virus belonged to genogroup 2b, we speculated that the reason a singular S gene exchange failed to reverse the virulence of the avirulent G1a CHM2013 strain might be due to, at least in part, the suboptimal cooperation between structural proteins in terms of PEDV morphogenesis.
T189 4014-4104 Sentence denotes Second, the degree of attenuation differed between the CHM2013 virus and PEDVPT-P96 virus.
T190 4105-4384 Sentence denotes Comparing to the avirulent CHM2013 virus that induced no detectable viral shedding in two-day-old piglets, iPEDVPT-P96 virus retained some levels of virulence as it caused viral shedding, observable clinical symptoms, and even mortality in the seven-day-old conventional piglets.
T191 4385-4615 Sentence denotes Besides the S gene [17,28], the abolishment of the function of non-structural proteins (NSPs) alone has been demonstrated to attenuate highly virulent PEDVs by disrupting the antagonistic ability of host interferons (IFN) [16,27].
T192 4616-4735 Sentence denotes That means, when the function of certain NSP was abated, PEDVs lose its virulence, regardless of the S gene they carry.
T193 4736-4950 Sentence denotes Therefore, variations of NSPs in the CHM2013 virus might have a critical effect on its virulence, and the effect might be stronger than that contributed by the S gene derived from the highly virulent BJ2011C virus.
T194 4951-5227 Sentence denotes Similarly, we also speculated that the IFN-suppressive function provided by NSP(s) might also contribute to virulent differences between the iPEDVPT-P5-96S and iPEDVPT-P96 since nine mutations were identified in NSPs in the iPEDVPT-P96 as compared with that of PEDVPT-P5 [18].
T195 5228-5309 Sentence denotes Regardless, further studies are needed to clarify the hypotheses mentioned above.
T196 5310-5492 Sentence denotes Sequence comparison between the autologous highly virulent PEDVPT-P5 and attenuated PEDVPT-P96 revealed several amino acid substitutions [18], especially in the S gene (see Table 1).
T197 5493-5633 Sentence denotes Consistent with other studies, these mutations chiefly accumulated in the S2 domain, presumably because of adaptation to Vero cells [12,29].
T198 5634-5954 Sentence denotes In the present study, the enhanced fusogenic ability in vitro was distinctly ascribed to the S gene, more specifically the S2 domain, derived from iPEDVPT-P96 and presumably represented the evolutionary process to increase viral progeny since Vero cells are not of swine-origin but readily susceptible to PEDV infection.
T199 5955-6205 Sentence denotes Animal experiments with seven-day-old piglets revealed that the exchange of the S gene from the iPEDVPT-P96 resulted in a delayed onset of peak viral shedding, diarrhea, and milder villous atrophy when examined histologically at 3 d post-inoculation.
T200 6206-6494 Sentence denotes Additionally, in contrast to the findings published by Wang et al. [17], Suzuki et al. [30] reported that replacement of the entire S gene or S1 sequence from a highly virulent OKN-1/JPN/2013 American type PEDV strain enabled the attenuated rPEDVGFP-CV777 to acquire virulence in piglets.
T201 6495-6652 Sentence denotes In iPEDVPT-P96 virus, however, only two amino acid substitutions were identified in the S10 (C144T) and S1B (T554C) domains compared to the iPEDVPT-P5 virus.
T202 6653-6807 Sentence denotes For PEDV, S10 and S1B domains are known to contain sialic acid-binding and receptor-binding domains, respectively; thus, are crucial for viral entry [31].
T203 6808-6991 Sentence denotes Although Hou et al. [23] previously showed that deletion of 197 amino acids in S10 domain of PEDV resulted in attenuation in piglets, a more specific epitope has yet to be identified.
T204 6992-7191 Sentence denotes Therefore, we are curious about whether only these two mutations in iPEDVPT-P96 can attenuate the highly virulent iPEDVPT-P5 virus or if the S2 domain must be primarily accounted for the attenuation.
T205 7192-7254 Sentence denotes Future studies will be conducted to elucidate these questions.
T206 7255-7504 Sentence denotes In this study, the first pair of cDNA clones for a virulent G2b PEDV, and its derived attenuated strain were generated, allowing us to use both gain-of-function and lose-of-function approaches to studying the role of the S gene in PEDV pathogenesis.
T207 7505-7656 Sentence denotes We confirmed that the S gene is a crucial virulent/attenuating determinant for the iPEDVPT-P96, but its importance varies among different PEDV strains.
T208 7657-7810 Sentence denotes Thus, other studies’ results alongside our results will provide valuable information for the future generation of novel chimeric or multivalent vaccines.