Nsp1 proteins of group I and SARS coronaviruses share structural and functional similarities

Wang, Yongjin; Shi, Huiling; Rigolet, Pascal; Wu, Nannan; Zhu, Linghua; Xi, Xu Guang; Vabret, Astrid; Wang, Xiaoming; Wang, Tianhou

doi:10.1016/j.meegid.2010.05.014

Cited by 33 publications

(42 citation statements)

References 40 publications

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“…Many viruses suppress host protein synthesis and modify host cell environments to promote virus-specific translation (Lloyd, 2006;Schneider and Mohr, 2003). The CoV nsp1 is a multifunctional protein involved in viral replication, pathogenesis, evasion from antiviral signaling, and suppression of host protein synthesis (Brockway and Denison, 2005;Kamitani et al, 2009Kamitani et al, , 2006Lokugamage et al, 2012;Narayanan et al, 2008;Wang et al, 2010;Wathelet et al, 2007;Züst et al, 2007). In alphacoronaviruses, the nsp1s of HCoV-229E, HCoV-NL63 and TGEV induce suppression of protein synthesis in mammalian cells (Huang et al, 2011a;Wang et al, 2010;Züst et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…The CoV nsp1 is a multifunctional protein involved in viral replication, pathogenesis, evasion from antiviral signaling, and suppression of host protein synthesis (Brockway and Denison, 2005;Kamitani et al, 2009Kamitani et al, , 2006Lokugamage et al, 2012;Narayanan et al, 2008;Wang et al, 2010;Wathelet et al, 2007;Züst et al, 2007). In alphacoronaviruses, the nsp1s of HCoV-229E, HCoV-NL63 and TGEV induce suppression of protein synthesis in mammalian cells (Huang et al, 2011a;Wang et al, 2010;Züst et al, 2007). In betacoronaviruses, the nsp1s of MHV, SARS-CoV and several bat CoVs also have the ability to induce translational suppression (Kamitani et al, 2006;Tohya et al, 2009;Züst et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Although the amino acid sequences of nsp3 to nsp16 are predicted to be conserved among CoVs, those of nsp1 are highly divergent (Connor and Roper, 2007). However, the nsp1s of several CoVs, such as porcine transmissible gastroenteritis virus (TGEV), human CoV (HCoV)-229E, mouse hepatitis virus (MHV), and SARS-CoV, exhibit a similar function to induce translational suppression (Huang et al, 2011a;Kamitani et al, 2006;Wang et al, 2010;Züst et al, 2007). The nsp1 of SARS-CoV is the most studied among CoVs and is known to inhibit host gene expression via a two-pronged strategy )-i.e., translational shutoff through interaction with the 40 S ribosomal subunit, and host mRNA degradation through the recruitment of unidentified host nuclease(s) (Huang et al, 2011a;Kamitani et al, 2009;Lokugamage et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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MERS coronavirus nsp1 participates in an efficient propagation through a specific interaction with viral RNA

et al. 2017

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MERS-CoV is the only lethal human CoV still endemic in the Arabian Peninsula and neither vaccine nor therapeutics against MERS-CoV infection is available. The nsp1 of CoV is thought to be a major virulence factor because it suppresses protein synthesis through the degradation of host mRNA. In contrast, viral RNA circumvents the nsp1-mediated translational shutoff for an efficient propagation. In this study, we identified amino acid residue in MERS-CoV nsp1 that differ from those of SARS-CoV nsp1, and that appear to be crucial for circumventing the translational shutoff. In addition, reverse genetics analysis suggested the presence of a cis-acting element at the 5'-terminus of the nsp1-coding region, which contributes to the specific recognition of viral RNA that is required for an efficient viral replication. Our results suggest the CoVs share a common mechanism for circumventing the nsp1-mediated translational shutoff.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MERS coronavirus nsp1 participates in an efficient propagation through a specific interaction with viral RNA

et al. 2017

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“…For nidoviruses, eleven and six viral proteins have been described as IFN antagonists for severe acute respiratory syndrome coronavirus (SARS-CoV) and porcine reproductive and respiratory syndrome virus (PRRSV), respectively Kindler and Thiel, 2014;Shi et al, 2014;Sun et al, 2012b;Totura and Baric, 2012). For Betacoronaviruses, nsp1 has been reported as a multifunctional viral antagonist for innate immune response (Huang et al, 2011b;Narayanan et al, 2008;Wang et al, 2010). For PEDV, the viral modulation of innate immune signaling is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Suppression of type I interferon production by porcine epidemic diarrhea virus and degradation of CREB-binding protein by nsp1

2016

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Type I interferons (IFN-α/β) are the major components of the innate immune response of hosts, and in turn many viruses have evolved to modulate the host response during infection. We found that the IFN-β production was significantly suppressed during PEDV infection in cells. To identify viral IFN antagonists and to study their suppressive function, viral coding sequences for the entire structural and nonstructural proteins were cloned and expressed. Of 16 PEDV nonstructural proteins (nsps), nsp1, nsp3, nsp7, nsp14, nsp15 and nsp16 were found to inhibit the IFN-β and IRF3 promoter activities. The sole accessory protein ORF3, structure protein envelope (E), membrane (M), and nucleocapsid (N) protein were also shown to inhibit such activities. PEDV nsp1 did not interfere the IRF3 phosphorylation and nuclear translocation but interrupted the enhanceosome assembly of IRF3 and CREB-binding protein (CBP) by degrading CBP. A further study showed that the CBP degradation by nsp1 was proteasome-dependent. Our data demonstrate that PEDV modulates the host innate immune responses by degrading CBP and suppressing ISGs expression.

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“…Transmissible gastroenteritis virus (TGEV) nsp1 cannot bind to the 40S subunit to affect the stability of host mRNA and suppresses translation through a putative host factor (43). The human CoV 229E and NL63 nsp1s are capable of inhibiting gene expression, possibly by binding to ribosomal subunit S6, which is part of the 40S subunit (44). PEDV nsp1 promotes the degradation of CBP and NF-B to inhibit the interferon (IFN) response (45,46), but the detailed mechanism of PEDV nsp1 inhibition of host protein synthesis is unclear.…”

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confidence: 99%

Structural Basis for the Inhibition of Host Gene Expression by Porcine Epidemic Diarrhea Virus nsp1

Shen

Deng

et al. 2018

J Virol

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Porcine epidemic diarrhea virus (PEDV), an enteropathogenic , has caused enormous economic losses in the pork industry. Nonstructural protein 1 (nsp1) is a characteristic feature of alpha- and betacoronaviruses, which exhibits both functional conservation and mechanistic diversity in inhibiting host gene expression and antiviral responses. However, the detailed structure and molecular mechanisms underlying the nsp1 inhibition of host gene expression remain unclear. Here, we report the first full-length crystal structure of nsp1 from PEDV. The structure displays a six-stranded β-barrel fold in the middle of two α-helices. The core structure of PEDV nsp1 shows high similarity to those of severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 and transmissible gastroenteritis virus (TGEV) nsp1, despite its low degree of sequence homology. Using ribopuromycylation and luciferase reporter assays, we showed that PEDV nsp1 can dramatically inhibit general host gene expression. Furthermore, three motifs (amino acids [aa] 67 to 71, 78 to 85, and 103 to 110) of PEDV nsp1 create a stable functional region for inhibiting protein synthesis, differing considerably from nsp1. These results elucidate the detailed structural basis through which PEDV nsp1 inhibits host gene expression, providing insight into the development of a new attenuated vaccine with nsp1 modifications. Porcine epidemic diarrhea virus (PEDV) has led to tremendous economic losses in the global swine industry. PEDV nsp1 plays a crucial role in inhibiting host gene expression, but its functional mechanism remains unclear. Here, we report the full-length structure of PEDV nsp1, the first among coronaviruses to be reported. The 1.25-Å resolution crystal structure of PEDV nsp1 shows high similarity to severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 and transmissible gastroenteritis virus (TGEV) nsp1, despite a lack of sequence homology. Structural and biochemical characterization demonstrated that PEDV nsp1 possesses a stable functional region for inhibition of host protein synthesis, which is formed by loops at residues 67 to 71, 78 to 85, and 103 to 110. The different functional regions in PEDV nsp1 and SARS-CoV nsp1 may explain their distinct mechanisms. Importantly, our structural data are conducive to understanding the mechanism of PEDV nsp1 inhibition of the expression of host genes and may aid in the development of a new attenuated vaccine.

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Nsp1 proteins of group I and SARS coronaviruses share structural and functional similarities

Cited by 33 publications

References 40 publications

MERS coronavirus nsp1 participates in an efficient propagation through a specific interaction with viral RNA

MERS coronavirus nsp1 participates in an efficient propagation through a specific interaction with viral RNA

Suppression of type I interferon production by porcine epidemic diarrhea virus and degradation of CREB-binding protein by nsp1

Structural Basis for the Inhibition of Host Gene Expression by Porcine Epidemic Diarrhea Virus nsp1

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