Mutations in Porcine Epidemic Diarrhea Virus nsp1 Cause Increased Viral Sensitivity to Host Interferon Responses and Attenuation
            <i>In Vivo</i>

Niu, Xiaoyu; Kong, Fanzhi; Xu, Jiayu; Liu, Mingde; Wang, Qiuhong

doi:10.1128/jvi.00469-22

Cited by 12 publications

(11 citation statements)

References 64 publications

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“…In addition to structure proteins, nonstructural proteins, including nsp1, nsp15, and nsp16, are also linked to the virulence of PEDV. Niu et al mutated two amino acids (N93A and N95A) in PEDV nsp1 and noted that the recombinant virus increased viral sensitivity to the host immune response and demonstrated an attenuation phenotype in vivo [52]. We also found that complement component 3 (C3) significantly inhibited PEDV replication in vitro; however, PEDV can antagonize the immune suppression of C3 via inhibition of the nsp1 phosphorylation of CEBP/β [59].…”

Section: Virulence Determinant Identificationmentioning

confidence: 64%

“…Identification of the virulence factors in CoVs is essential for the rational design of live-attenuated vaccine candidates. To date, an extensive effort has been made toward understanding the virulence factors of the emerging and re-emerging swine CoVs [48][49][50][51][52][53][54][55]. Many studies have suggested that the virulence of PEDV is associated with its S protein.…”

Section: Virulence Determinant Identificationmentioning

confidence: 99%

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Reverse Genetics Systems for Emerging and Re-Emerging Swine Coronaviruses and Applications

Jiang,

Wang,

Kong

et al. 2023

Viruses

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Emerging and re-emerging swine coronaviruses (CoVs), including porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome-CoV (SADS-CoV), cause severe diarrhea in neonatal piglets, and CoV infection is associated with significant economic losses for the swine industry worldwide. Reverse genetics systems realize the manipulation of RNA virus genome and facilitate the development of new vaccines. Thus far, five reverse genetics approaches have been successfully applied to engineer the swine CoV genome: targeted RNA recombination, in vitro ligation, bacterial artificial chromosome-based ligation, vaccinia virus -based recombination, and yeast-based method. This review summarizes the advantages and limitations of these approaches; it also discusses the latest research progress in terms of their use for virus-related pathogenesis elucidation, vaccine candidate development, antiviral drug screening, and virus replication mechanism determination.

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Section: Virulence Determinant Identificationmentioning

confidence: 64%

Section: Virulence Determinant Identificationmentioning

confidence: 99%

Reverse Genetics Systems for Emerging and Re-Emerging Swine Coronaviruses and Applications

Jiang,

Wang,

Kong

et al. 2023

Viruses

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“…Multiple proteins of PEDV have been shown to inhibit IFN responses during infection (214)(215)(216)(217)(218)(219). The nsp1 protein of PEDV is the most potent viral IFN antagonist (214), and three residues of F44, N93, and N95 of nsp1 are critical for both type I and type III IFN suppression (52,220). PEDV nsp1 suppressed both types of IFN responses by interrupting the IRF3 and CREB-binding protein association and suppressing transcription factors (52) (Figure 1).…”

Section: Porcine Epidemic Diarrhea Virusmentioning

confidence: 99%

“…A replication-competent PEDV mutant with an IFN inactive version of nsp1 induced IFN response in IFN-responsive cells ( 52 ). It was further demonstrated that PEDV carrying the nsp1 N93/95A mutation triggered a significantly higher level of IFN response and induced 100% protection from severe diarrhea and death in neonatal piglets post-challenge ( 220 ). These findings suggest that nsp1 is an essential virulence determinant for CoVs, providing a potential paradigm for the development of a new vaccine based on IFN modification.…”

Section: Reprograming Viral Immune Evasion and Experimental Infection...mentioning

confidence: 99%

Reprogramming viral immune evasion for a rational design of next-generation vaccines for RNA viruses

Rowland

et al. 2023

Front. Immunol.

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Type I interferons (IFNs-α/β) are antiviral cytokines that constitute the innate immunity of hosts to fight against viral infections. Recent studies, however, have revealed the pleiotropic functions of IFNs, in addition to their antiviral activities, for the priming of activation and maturation of adaptive immunity. In turn, many viruses have developed various strategies to counteract the IFN response and to evade the host immune system for their benefits. The inefficient innate immunity and delayed adaptive response fail to clear of invading viruses and negatively affect the efficacy of vaccines. A better understanding of evasion strategies will provide opportunities to revert the viral IFN antagonism. Furthermore, IFN antagonism-deficient viruses can be generated by reverse genetics technology. Such viruses can potentially serve as next-generation vaccines that can induce effective and broad-spectrum responses for both innate and adaptive immunities for various pathogens. This review describes the recent advances in developing IFN antagonism-deficient viruses, their immune evasion and attenuated phenotypes in natural host animal species, and future potential as veterinary vaccines.

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“…It targets host translation machinery and the interferon (IFN) response system to induce host mRNA degradation and antagonize IFN responses [45][46][47][48]. The replication-transcription complex (RTC), responsible for viral RNA synthesis, consists of multiple viral nonstructural proteins [49][50][51]. Among the proteins involved in the RTC, nsp3-nsp6 are responsible for modulating intracellular membranes and assembling double-membrane vesicles (DMV), where viral RNA synthesis occurs [52,53].…”

Section: Pedv Replication and Functional Elements In Transcriptionmentioning

confidence: 99%

Prevention and Control of Porcine Epidemic Diarrhea: The Development of Recombination-Resistant Live Attenuated Vaccines

Niu

Wang

2022

Viruses

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Porcine epidemic diarrhea (PED), causing up to 100% mortality in neonatal pigs, is a highly contagious enteric disease caused by PED virus (PEDV). The highly virulent genogroup 2 (G2) PEDV emerged in 2010 and has caused huge economic losses to the pork industry globally. It was first reported in the US in 2013, caused country-wide outbreaks, and posed tremendous hardship for many pork producers in 2013–2014. Vaccination of pregnant sows/gilts with live attenuated vaccines (LAVs) is the most effective strategy to induce lactogenic immunity in the sows/gilts and provide a passive protection via the colostrum and milk to suckling piglets against PED. However, there are still no safe and effective vaccines available after about one decade of endeavor. One of the biggest concerns is the potential reversion to virulence of an LAV in the field. In this review, we summarize the status and the major obstacles in PEDV LAV development. We also discuss the function of the transcriptional regulatory sequences in PEDV transcription, contributing to recombination, and possible strategies to prevent the reversion of LAVs. This article provides insights into the rational design of a promising LAV without safety issues.

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Mutations in Porcine Epidemic Diarrhea Virus nsp1 Cause Increased Viral Sensitivity to Host Interferon Responses and Attenuation In Vivo

Cited by 12 publications

References 64 publications

Reverse Genetics Systems for Emerging and Re-Emerging Swine Coronaviruses and Applications

Reverse Genetics Systems for Emerging and Re-Emerging Swine Coronaviruses and Applications

Reprogramming viral immune evasion for a rational design of next-generation vaccines for RNA viruses

Prevention and Control of Porcine Epidemic Diarrhea: The Development of Recombination-Resistant Live Attenuated Vaccines

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