Nonstructural protein 9 residues 586 and 592 are critical sites in determining the replication efficiency and fatal virulence of the Chinese highly pathogenic porcine reproductive and respiratory syndrome virus

Xu, Lei; Zhou, Lei; Sun, Weifeng; Zhang, Pingping; Ge, Xinna; Guo, Xin; Han, Jun; Yang, Hanchun

doi:10.1016/j.virol.2018.01.018

Cited by 25 publications

(24 citation statements)

References 62 publications

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“…The virulence determinants of HP‐PRRSV2 isolates were widely studied, which showed that the unique discontinuous 30‐amino‐acid deletion in nsp2 is not associated with the enhanced virulence, but nsp9 and nsp10 contribute to the increased virulence of HP‐PRRSV2 (Li et al., 2014; Zhou et al., 2009). In addition, several specific residues associated with the virulence have also been identified (Xu et al., 2018; Zhao et al., 2018). However, the underlying mechanisms associated with the attenuation of HP‐PRRS MLVs are rarely reported.…”

Section: Resultsmentioning

confidence: 99%

“…Nsp9 has RNA‐dependent RNA polymerase (RdRp) activity and nsp10 possesses RNA helicase activity, which both play crucial roles in virus replication (Xu et al., 2018). In addition, the enhanced replication efficiency is associated with the high virulence of HP‐PRRSV2 (Xu et al., 2018; Zhao et al., 2018). Currently, the determinants of HP‐PRRSV2 replication efficiency are still not well clarified.…”

Section: Resultsmentioning

confidence: 99%

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The infectious cDNA clone of commercial HP‐PRRS JXA1‐R‐attenuated vaccine can be a potential effective live vaccine vector

Chen

et al. 2020

Transbound Emerg Dis

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Multiple commercial porcine reproductive and respiratory syndrome (PRRS) modified live vaccines are currently utilized in Chinese swine herds due to the limited cross‐protection of vaccines and coexistence of different PRRS viruses. In this study, an infectious cDNA clone of the highly pathogenic PRRS (HP‐PRRS) vaccine JXA1‐R strain was generated. We successfully rescued the virus from direct in vitro DNA transfection of rJXA1‐R clone, which has similar growth kinetics to the parental JXA1‐R virus in Marc‐145 cells. To further evaluate the potential use of the cloned rJXA1‐R virus as a live vector for foreign gene expression, the enhanced green fluorescent protein (EGFP) was inserted between non‐structural and structural genes. Our results showed that the dynamic expression of EGFP can be visualized by live cell imaging system during the infection in Marc‐145 cells. The availability of our cloned JXA1‐R viruses provides a crucial platform to study the fundamental biology of HP‐PRRS virus vaccine and also serves as a potential effective vector for developing live vector vaccines against swine pathogens.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The infectious cDNA clone of commercial HP‐PRRS JXA1‐R‐attenuated vaccine can be a potential effective live vaccine vector

Chen

et al. 2020

Transbound Emerg Dis

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“…As the arterivirus RNA polymerase, Nsp9 has been recognized as a core component of RTCs, and PRRSV Nsp9 plays a central role in the RTC machinery and interacts with the N protein [36], Nsp7α [37], Nsp1α, Nsp1β, Nsp3, Nsp7β, Nsp8, Nsp11, and Nsp12 [17]. Furthermore, RNA synthesis efficiency correlates closely with Nsp9 and consistently with PRRSV virulence [13,38,39]. Nonetheless, arterivirus sgmRNA synthesis depends on the Nsp1 autoprotease [10,40,41].…”

Section: Discussionmentioning

confidence: 99%

The Nsp12-coding region of type 2 PRRSV is required for viral subgenomic mRNA synthesis

Wang

Fang

Feng

et al. 2019

Emerging Microbes & Infections

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As one of many nonstructural proteins of porcine reproductive and respiratory syndrome virus (PRRSV), nonstructural protein 12 (Nsp12) has received relatively little attention, and its role in virus replication, if any, is essentially unknown. By the application of reverse genetic manipulation of an infectious PRRSV clone, the current study is the first to demonstrate that Nsp12 is a key component of PRRSV replication. In addition, the biochemical properties of Nsp12 were evaluated, revealing that Nsp12 forms dimers when exposed to oxidative conditions. Furthermore, we systemically analyzed the function of Nsp12 in PRRSV RNA synthesis using a strand-specific PCR method. To our surprise, Nsp12 was not found to be involved in minus-strand genomic RNA (-gRNA) synthesis; importantly, our results indicate that Nsp12 is involved in the synthesis of both plus- and minus-strand subgenomic mRNAs (+sgmRNA and -sgmRNA). Finally, we found that the combination of cysteine 35 and cysteine 79 in Nsp12 is required for sgmRNA synthesis. To our knowledge, we are the first to report the biological role of Nsp12 in the PRRSV lifecycle, and we conclude that Nsp12 is involved in the synthesis of both + sgRNA and -sgRNA.

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“…Nsp9, the key enzyme encoded by ORF1b for RNA-templated RNA synthesis (RdRp) (Fang and Snijder, 2010), is closely related to the replication efficiency and pathogenicity for piglets (Li et al, 2014b;Music and Gagnon, 2010;Xu et al, 2018;Zhao et al, 2018). As a consequence, several host proteins have been reported to interact with PRRSV Nsp9.…”

Section: Discussionmentioning

confidence: 99%

Nucleotide-binding oligomerization domain-like receptor X1 restricts porcine reproductive and respiratory syndrome virus-2 replication by interacting with viral Nsp9

et al. 2019

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Porcine reproductive and respiratory syndrome virus (PRRSV) causes one of the most economically important diseases of swine worldwide. Current antiviral strategies provide only limited protection. Nucleotide-binding oligomerization domain-like receptor (NLR) X1 is unique among NLR proteins in its functions as a pro-viral or antiviral factor to different viral infections. To date, the impact of NLRX1 on PRRSV infection remains unclear. In this study, we found that PRRSV infection promoted the expression of NLRX1 gene. In turn, ectopic expression of NLRX1 inhibited PRRSV replication in Marc-145 cells, whereas knockdown of NLRX1 enhanced PRRSV propagation in porcine alveolar macrophages (PAMs). Mechanistically, NLRX1 was revealed to impair intracellular viral subgenomic RNAs accumulation. Finally, Mutagenic analyses indicated that the LRR (leucine-rich repeats) domain of NLRX1 interacted with PRRSV Nonstructural Protein 9 (Nsp9) RdRp (RNA-dependent RNA Polymerase) domain and was necessary for antiviral activity. Thus, our study establishes the role of NLRX1 as a new host restriction factor in PRRSV infection.

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Nonstructural protein 9 residues 586 and 592 are critical sites in determining the replication efficiency and fatal virulence of the Chinese highly pathogenic porcine reproductive and respiratory syndrome virus

Cited by 25 publications

References 62 publications

The infectious cDNA clone of commercial HP‐PRRS JXA1‐R‐attenuated vaccine can be a potential effective live vaccine vector

The infectious cDNA clone of commercial HP‐PRRS JXA1‐R‐attenuated vaccine can be a potential effective live vaccine vector

The Nsp12-coding region of type 2 PRRSV is required for viral subgenomic mRNA synthesis

Nucleotide-binding oligomerization domain-like receptor X1 restricts porcine reproductive and respiratory syndrome virus-2 replication by interacting with viral Nsp9

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