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Crystal Structure of Classical Swine Fever Virus NS5B Reveals a Novel N-Terminal Domain.

Li W, Wu B, Soca WA, An L
J Virol 92 (2018)
Cited: 16 times
EuropePMC logo PMID: 29720518

Abstract

Classical swine fever virus (CSFV) is the cause of classical swine fever (CSF). Nonstructural protein 5B (NS5B) is an RNA-dependent RNA polymerase (RdRp) that is a key enzyme initiating viral RNA replication by a de novo mechanism. It is also an attractive target for the development of anti-CSFV drugs. To gain a better understanding of the mechanism of CSFV RNA synthesis, here, we solved the first crystal structure of CSFV NS5B. Our studies show that the CSFV NS5B RdRp contains the characteristic finger, palm, and thumb domains, as well as a unique N-terminal domain (NTD) that has never been observed. Mutagenesis studies on NS5B validated the importance of the NTD in the catalytic activity of this novel RNA-dependent RNA polymerase. Moreover, our results shed light on CSFV infection.

Reviews - 5y6r mentioned but not cited (2)

  1. Atypical Porcine Pestiviruses: Relationships and Conserved Structural Features. Riedel C, Aitkenhead H, El Omari K, Rümenapf T. Viruses 13 760 (2021)
  2. Revisiting Viral RNA-Dependent RNA Polymerases: Insights from Recent Structural Studies. Ramaswamy K, Rashid M, Ramasamy S, Jayavelu T, Venkataraman S. Viruses 14 2200 (2022)

Articles - 5y6r mentioned but not cited (6)

  1. A unique intra-molecular fidelity-modulating mechanism identified in a viral RNA-dependent RNA polymerase. Liu W, Shi X, Gong P. Nucleic Acids Res 46 10840-10854 (2018)
  2. Crystal Structure of Classical Swine Fever Virus NS5B Reveals a Novel N-Terminal Domain. Li W, Wu B, Soca WA, An L. J Virol 92 e00324-18 (2018)
  3. Crystal structures of alphavirus nonstructural protein 4 (nsP4) reveal an intrinsically dynamic RNA-dependent RNA polymerase fold. Tan YB, Lello LS, Liu X, Law YS, Kang C, Lescar J, Zheng J, Merits A, Luo D. Nucleic Acids Res 50 1000-1016 (2022)
  4. Crystal structure of a tick-borne flavivirus RNA-dependent RNA polymerase suggests a host adaptation hotspot in RNA viruses. Yang J, Jing X, Yi W, Li XD, Yao C, Zhang B, Zheng Z, Wang H, Gong P. Nucleic Acids Res 49 1567-1580 (2021)
  5. An induced-fit de novo initiation mechanism suggested by a pestivirus RNA-dependent RNA polymerase. Zhang BY, Liu W, Jia H, Lu G, Gong P. Nucleic Acids Res 49 8811-8821 (2021)
  6. Structure Prediction and Analysis of Hepatitis E Virus Non-Structural Proteins from the Replication and Transcription Machinery by AlphaFold2. Goulet A, Cambillau C, Roussel A, Imbert I. Viruses 14 1537 (2022)


Reviews citing this publication (1)

  1. A Structure-Function Diversity Survey of the RNA-Dependent RNA Polymerases From the Positive-Strand RNA Viruses. Jia H, Gong P. Front Microbiol 10 1945 (2019)

Articles citing this publication (7)

  1. A nucleobase-binding pocket in a viral RNA-dependent RNA polymerase contributes to elongation complex stability. Shi W, Ye HQ, Deng CL, Li R, Zhang B, Gong P. Nucleic Acids Res 48 1392-1405 (2020)
  2. Characteristics of Classical Swine Fever Virus Variants Derived from Live Attenuated GPE- Vaccine Seed. Kim T, Huynh LT, Hirose S, Igarashi M, Hiono T, Isoda N, Sakoda Y. Viruses 13 1672 (2021)
  3. Molecular architecture of the Chikungunya virus replication complex. Tan YB, Chmielewski D, Law MCY, Zhang K, He Y, Chen M, Jin J, Luo D. Sci Adv 8 eadd2536 (2022)
  4. Determination of Critical Requirements for Classical Swine Fever Virus NS2-3-Independent Virion Formation. Dubrau D, Schwindt S, Klemens O, Bischoff H, Tautz N. J Virol 93 e00679-19 (2019)
  5. Structural basis of transition from initiation to elongation in de novo viral RNA-dependent RNA polymerases. Wu J, Wang X, Liu Q, Lu G, Gong P. Proc Natl Acad Sci U S A 120 e2211425120 (2023)
  6. Proline to Threonine Mutation at Position 162 of NS5B of Classical Swine Fever Virus Vaccine C Strain Promoted Genome Replication and Infectious Virus Production by Facilitating Initiation of RNA Synthesis. Pang H, Li L, Liu H, Pan Z. Viruses 13 1523 (2021)
  7. Anti-BVDV Activity of Traditional Chinese Medicine Monomers Targeting NS5B (RNA-Dependent RNA Polymerase) In Vitro and In Vivo. Chen N, Jiang D, Shao B, Bai T, Chen J, Liu Y, Zhang Z, Zhou Y, Wang X, Zhu Z. Molecules 28 3413 (2023)


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