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

Authors

Lalit Beura, University of Nebraska-LincolnFollow
Sakthivel Subramaniam, University of Nebraska-LincolnFollow
Hiep Vu, University of Nebraska-LincolnFollow
Byungjoon Kwon, University of Nebraska - Lincoln
Asit K. Pattnaik, University of Nebraska-LincolnFollow
Fernando A. Osorio, University of Nebraska - LincolnFollow

Document Type

Article

Date of this Version

2012

Citation

Virology 433(2012)431–439

Comments

2012 Elsevier Inc. All rights reserved.

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 IFNsuppression. A mutant virus (16-SA, 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-SA 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.