1887

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Volume 99, Issue 1

Restoration of glycoprotein E dimerization via pseudoreversion partially restores virulence of classical swine fever virus Free

Abstract

The classical swine fever virus (CSFV) represents one of the most important pathogens of swine. The CSFV glycoprotein E is an essential structural protein and an important virulence factor. The latter is dependent on the RNase activity of this envelope protein and, most likely, its secretion from the infected cell. A further important feature with regard to its function as a virulence factor is the formation of disulfide-linked E homodimers that are found in virus-infected cells and virions. Mutant CSFV lacking cysteine (Cys) 171, the residue responsible for intermolecular disulfide bond formation, were found to be attenuated in pigs (Tews BA, Schürmann EM, Meyers G. 2009;83:4823–4834). In the course of an animal experiment with such a dimerization-negative CSFV mutant, viruses were reisolated from pigs that contained a mutation of serine (Ser) 209 to Cys. This mutation restored the ability to form disulphide-linked E homodimers. In transient expression studies E mutants carrying the S209C change were found to form homodimers with about wt efficiency. Also the secretion level of the mutated proteins was equivalent to that of wt E. Virus mutants containing the Cys171Ser/Ser209Cys configuration exhibited wt growth rates and increased virulence when compared with the Cys171Ser mutant. These results provide further support for the connection between CSFV virulence and E dimerization.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): envelope protein , interferon , pestivirus , protein dimerization and RNase
© 2018 The Authors
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2018-01-01
2024-04-24
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Restoration of glycoprotein Erns dimerization via pseudoreversion partially restores virulence of classical swine fever virus
J. Gen. Virol. 99, 86 (2018); https://doi.org/10.1099/jgv.0.000990
/content/journal/jgv/10.1099/jgv.0.000990
/content/journal/jgv/10.1099/jgv.0.000990
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