Tula and Puumala hantavirus NSs ORFs are functional and the products inhibit activation of the interferon-beta promoter

Jaaskelainen, K.M., Kaukinen, P., Minskaya, E.S., Plyusnina, A., Vapalahti, O., Elliott, R.M., Weber, F., Vaheri, A. and Plyusnin, A. (2007) Tula and Puumala hantavirus NSs ORFs are functional and the products inhibit activation of the interferon-beta promoter. Journal of Medical Virology, 79(10), pp. 1527-1536. (doi: 10.1002/jmv.20948)

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Abstract

The S RNA genome segment of hantaviruses carried by Arvicolinae and Sigmodontinae rodents encodes the nucleocapsid (N) protein and has an overlapping (+1) open reading frame (ORF) for a putative nonstructural protein (NSs). The aim of this study was to determine whether the ORF is functional. A protein corresponding to the predicted size of Tula virus (TULV) NSs was detected using coupled in vitro transcription and translation from a cloned S segment cDNA, and a protein corresponding to the predicted size of Puumala virus (PUUV) NSs was detected in infected cells by Western blotting with an anti-peptide serum. The activities of the interferon beta (IFN-β) promoter, and nuclear factor kappa B (NF-κB)- and interferon regulatory factor-3 (IRF-3) responsive promoters, were inhibited in COS-7 cells transiently expressing TULV or PUUV NSs. Also IFN-β mRNA levels in IFN-competent MRC5 cells either infected with TULV or transiently expressing NSs were decreased. These data demonstrate that Tula and Puumala hantaviruses have a functional NSs ORF. The findings may explain why the NSs ORF has been preserved in the genome of most hantaviruses during their long evolution and why hantavirus-infected cells secrete relatively low levels of IFNs. J. Med. Virol. 79:1527–1536, 2007. © Wiley-Liss, Inc.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Elliott, Professor Richard
Authors: Jaaskelainen, K.M., Kaukinen, P., Minskaya, E.S., Plyusnina, A., Vapalahti, O., Elliott, R.M., Weber, F., Vaheri, A., and Plyusnin, A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Medical Virology
ISSN:0146-6615
ISSN (Online):1096-9071
Published Online:17 August 2007

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