Identification of amino acid residues important for anti-IFN activity of porcine reproductive and respiratory syndrome virus non-structural protein 1

Lalit K. Beura, Sakthivel Subramaniam, Hiep L X Vu, Byungjoon Kwon, Asit K. Pattnaik, Fernando A. Osorio

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The non-structural protein 1 (nsp1) of porcine reproductive and respiratory syndrome virus is partly responsible for inhibition of type I interferon (IFN) response by the infected host. By performing alanine-scanning mutagenesis, we have identified amino acid residues in nsp1α and nsp1Β (the proteolytic products of nsp1) that when substituted with alanine(s) exhibited significant relief of IFN-suppression. A mutant virus (16-5A, in which residues 16-20 of nsp1Β were substituted with alanines) encoding mutant nsp1Β recovered from infectious cDNA clone was shown to be attenuated for growth in vitro and induced significantly higher amount of type I IFN transcripts in infected macrophages. In infected pigs, the 16-5A virus exhibited reduced growth at early times after infection but quickly regained wild type growth properties as a result of substitutions within the mutated sequences. The results indicate a strong selection pressure towards maintaining the IFN-inhibitory property of the virus for successful propagation in pigs.

Original languageEnglish (US)
Pages (from-to)431-439
Number of pages9
JournalVirology
Volume433
Issue number2
DOIs
StatePublished - Nov 25 2012

Keywords

  • Innate immunity
  • Non-structural protein 1α and 1Β
  • PRRSV
  • Type-1 interferon inhibition

ASJC Scopus subject areas

  • Virology

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