Deciphering the biology of porcine epidemic diarrhea virus in the era of reverse genetics

Teeravechyan, Samaporn; Frantz, Phanramphoei Namprachan; Wongthida, Phonphimon; Chailangkarn, Thanathom; Jaru-Ampornpan, Peera; Koonpaew, Surapong; Jongkaewwattana, Anan

doi:10.1016/j.virusres.2016.05.003

Cited by 27 publications

(32 citation statements)

References 159 publications

(184 reference statements)

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“…However, recently, it was demonstrated that PEDV is genetically more closely related to BtCoV/512/2005 than to TGEV, leading to the hypothesis that PEDV may have originated from bats ( Figure 2) [47 ]. Additionally, PEDV infects cells from pigs, humans, monkeys, duck, and bats, further supporting the theory that PEDV had crossed the batswine interspecies barrier sometime in the past (Table 1) [48,49]. PEDV has been detected from feral pigs in Korea and the US [50,51 ], with the latter study suggesting that PEDV may have spilled over from domestic to feral pigs.…”

Section: Origin and Potential For Intra/interspecies Transmissionmentioning

confidence: 75%

Emerging and re-emerging coronaviruses in pigs

Wang

Vlasova

Kenney

et al. 2019

Current Opinion in Virology

321

323

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Section: Origin and Potential For Intra/interspecies Transmissionmentioning

confidence: 75%

Emerging and re-emerging coronaviruses in pigs

Wang

Vlasova

Kenney

et al. 2019

Current Opinion in Virology

321

323

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“…These mutations probably facilitated the rescue of recombinant viruses in Vero cells but may impair the pathogenicity of recombinant AVCT12 (rAVCT12) in vivo. A review article summarizing different reverse genetics platforms for PEDV was recently published (52).…”

Section: Figmentioning

confidence: 99%

Deletion of a 197-Amino-Acid Region in the N-Terminal Domain of Spike Protein Attenuates Porcine Epidemic Diarrhea Virus in Piglets

Hou

Lin

Yokoyama

et al. 2017

J Virol

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We previously isolated a porcine epidemic diarrhea virus (PEDV) strain, PC177, by blind serial passaging of the intestinal contents of a diarrheic piglet in Vero cell culture. Compared with the highly virulent U.S. PEDV strain PC21A, the tissue culture-adapted PC177 (TC-PC177) contains a 197-amino-acid (aa) deletion in the N-terminal domain of the spike (S) protein. We orally inoculated neonatal, conventional suckling piglets with TC-PC177 or PC21A to compare their pathogenicities. Within 7 days postinoculation, TC-PC177 caused mild diarrhea and lower fecal viral RNA shedding, with no mortality, whereas PC21A caused severe clinical signs and 55% mortality. To investigate whether infection with TC-PC177 can induce crossprotection against challenge with a highly virulent PEDV strain, all the surviving piglets were challenged with PC21A at 3 weeks postinoculation. Compared with 100% protection in piglets initially inoculated with PC21A, 88% and 100% TC-PC177-and mock-inoculated piglets had diarrhea following challenge, respectively, indicating incomplete cross-protection. To investigate whether this 197-aa deletion was the determinant for the attenuation of TC-PC177, we generated a mutant (icPC22A-S1Δ197) bearing the 197-aa deletion from an infectious cDNA clone of the highly virulent PEDV PC22A strain (infectious clone PC22A, icPC22A). In neonatal gnotobiotic pigs, the icPC22A-S1Δ197 virus caused mild to moderate diarrhea, lower titers of viral shedding, and no mortality, whereas the icPC22A virus caused severe diarrhea and 100% mortality. Our data indicate that deletion of this 197-aa fragment in the spike protein can attenuate a highly virulent PEDV, but the virus may lose important epitopes for inducing robust protective immunity.IMPORTANCE The emerging, highly virulent PEDV strains have caused substantial economic losses worldwide. However, the virulence determinants are not established. In this study, we found that a 197-aa deletion in the N-terminal region of the S protein did not alter virus (TC-PC177) tissue tropism but reduced the virulence of the highly virulent PEDV strain PC22A in neonatal piglets. We also demonstrated that the primary infection with TC-PC177 failed to induce complete cross-protection against challenge by the highly virulent PEDV PC21A, suggesting that the 197-aa region may contain important epitopes for inducing protective immunity. Our results provide an insight into the role of this large deletion in virus propagation and pathogenicity. In addition, the reverse genetics platform of the PC22A strain was further optimized for the rescue of recombinant PEDV viruses in vitro. This break-

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“…Reverse genetics technology provides a useful tool to molecular biology against the pathogenesis of PEDV (47). Although several reverse genetics systems have been established for PEDV (48)(49)(50)(51), its application to identification of virulence determinants has been rare (47,49,52). A recent study reported that a mutant (icPC22A-S1Δ197) bearing a 197-aa deletion in the N-terminal domain of S from an infectious cDNA clone of the highly virulent PEDV PC22A is attenuated in piglets (52).…”

Section: Importancementioning

confidence: 99%

The S Gene Is Necessary but Not Sufficient for the Virulence of Porcine Epidemic Diarrhea Virus Novel Variant Strain BJ2011C

Wang

Chen

et al. 2018

J Virol

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The recently emerged highly virulent variants of porcine epidemic diarrhea virus (PEDV) have caused colossal economic losses to the worldwide swine industry. In this study, we investigated the viral virulence determinants by constructing a series of chimeric mutants between the highly virulent strain BJ2011C and the avirulent strain CHM2013. When tested in the 2-day-old piglet model, wild-type (WT) BJ2011C caused severe diarrhea and death of the piglets within 72 h. In contrast, its chimeric derivative carrying the S gene from CHM2013 (BJ2011C-S) was avirulent to the piglets. Moreover, reciprocal substitution of the BJ2011C S gene (CHM2013-S) did not enable CHM2013 to gain any virulence. However, when the whole structural protein-coding region of BJ2011C (CHM2013-SP) was swapped, CHM2013 started to gain the ability to efficiently colonize the intestinal tract and caused diarrhea in piglets. A further gain of virulence required additional acquisition of the 3' untranslated region (UTR) of BJ2011C, and the resultant virus (CHM2013-SP + 3UTR) caused more severe diarrhea and death of piglets. Together, our findings suggest that the virulence of PEDV epidemic strains is a multigenic event and that the S gene is only one of the necessary determinants. The recently emerged highly virulent PEDV variants are the major cause of the global porcine epidemic diarrhea (PED) pandemic. The S gene of the variants undergoes remarkable variations and has been thought to be the virulence determinant for the enhanced pathogenesis. Our studies here showed that the S gene is only part of the story and that full virulence requires cooperation from other genes. Our findings provide insight into the pathogenic mechanism of the highly virulent PEDV variants and have implications for future vaccine development.

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Deciphering the biology of porcine epidemic diarrhea virus in the era of reverse genetics

Cited by 27 publications

References 159 publications

Emerging and re-emerging coronaviruses in pigs

Emerging and re-emerging coronaviruses in pigs

Deletion of a 197-Amino-Acid Region in the N-Terminal Domain of Spike Protein Attenuates Porcine Epidemic Diarrhea Virus in Piglets

The S Gene Is Necessary but Not Sufficient for the Virulence of Porcine Epidemic Diarrhea Virus Novel Variant Strain BJ2011C

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