Identification of an NTPase motif in classical swine fever virus NS4B protein
| Autor: | Manuel V. Borca, Boris Gavrilov, Vivian O'Donnell, Lauren G. Holinka, Nino G. Vepkhvadze, Guillermo R. Risatti, Ignacio Fernandez-Sainz, Kara Rogers, Douglas P. Gladue |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Swine
viruses Molecular Sequence Data Virulence Replication Viral Nonstructural Proteins Classical swine fever virus Virus Conserved sequence Classical Swine Fever Flaviviridae Nucleotide binding domain Adenosine Triphosphate Catalytic Domain Virology Animals Amino Acid Sequence Viremia NS4B protein Conserved Sequence NTPase activity Binding Sites biology Hydrolysis Pestivirus Walker motifs RNA virus Viral Load biology.organism_classification Nucleoside-Triphosphatase Amino Acid Substitution Classical swine fever Mutagenesis Site-Directed Mutant Proteins Guanosine Triphosphate Sequence Alignment |
| Zdroj: | Virology. 411(1):41-49 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2010.12.028 |
| Popis: | Classical swine fever (CSF) is a highly contagious and often fatal disease of swine caused by CSF virus (CSFV), a positive-sense single-stranded RNA virus within the Pestivirus genus of the Flaviviridae family. Here, we have identified conserved sequence elements observed in nucleotide-binding motifs (NBM) that hydrolyze NTPs within the CSFV non-structural (NS) protein NS4B. Expressed NS4B protein hydrolyzes both ATP and GTP. Substitutions of critical residues within the identified NS4B NBM Walker A and B motifs significantly impair the ATPase and GTPase activities of expressed proteins. Similar mutations introduced into the genetic backbone of a full-length cDNA copy of CSFV strain Brescia rendered no infectious viruses or viruses with impaired replication capabilities, suggesting that this NTPase activity is critical for the CSFV cycle. Recovered mutant viruses retained a virulent phenotype, as parental strain Brescia, in infected swine. These results have important implications for developing novel antiviral strategies against CSFV infection. |
| Databáze: | OpenAIRE |
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