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

KM Jääskeläinen; KM Kaukinen; ES Minskaya; A Plyusnina; O Vapalahti; Richard Michael Elliott; F Weber; A Vaheri; A Plyusnin

doi:10.1002/jmv.20948

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

KM Jääskeläinen, KM Kaukinen, ES Minskaya, A Plyusnina, O Vapalahti, Richard Michael Elliott, F Weber, A Vaheri, A Plyusnin

Research output: Contribution to journal › Article › peer-review

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-beta) promoter, and nuclear factor kappa B (NF-kappa beta)- and interferon regulatory factor-3 (IRF-3) responsive promoters, were inhibited in COS-7 cells transiently expressing TULV or PUUV NSs. Also IFN-beta 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 ORE 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 lFNs.

Original language	English
Pages (from-to)	1527-1536
Number of pages	10
Journal	Journal of Medical Virology
Volume	79
Issue number	10
DOIs	https://doi.org/10.1002/jmv.20948
Publication status	Published - Oct 2007

Keywords

hantavirus
TULV
PUUV
NSs ORF
innate immunity
IFN
NONSTRUCTURAL PROTEIN NSS
NUCLEOCAPSID PROTEIN
ENDOTHELIAL-CELLS
FEVER VIRUS
NONPATHOGENIC HANTAVIRUSES
HEMORRHAGIC-FEVER
RNA-POLYMERASE
HANTAAN VIRUS
I INTERFERON
MXA PROTEIN

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10.1002/jmv.20948

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@article{d7f28878451841bb9b08a4ec2208abab,

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

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-beta) promoter, and nuclear factor kappa B (NF-kappa beta)- and interferon regulatory factor-3 (IRF-3) responsive promoters, were inhibited in COS-7 cells transiently expressing TULV or PUUV NSs. Also IFN-beta 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 ORE 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 lFNs.",

keywords = "hantavirus, TULV, PUUV, NSs ORF, innate immunity, IFN, NONSTRUCTURAL PROTEIN NSS, NUCLEOCAPSID PROTEIN, ENDOTHELIAL-CELLS, FEVER VIRUS, NONPATHOGENIC HANTAVIRUSES, HEMORRHAGIC-FEVER, RNA-POLYMERASE, HANTAAN VIRUS, I INTERFERON, MXA PROTEIN",

author = "KM J{\"a}{\"a}skel{\"a}inen and KM Kaukinen and ES Minskaya and A Plyusnina and O Vapalahti and Elliott, {Richard Michael} and F Weber and A Vaheri and A Plyusnin",

year = "2007",

month = oct,

doi = "10.1002/jmv.20948",

language = "English",

volume = "79",

pages = "1527--1536",

journal = "Journal of Medical Virology",

issn = "0146-6615",

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TY - JOUR

T1 - Tula and Puumala hantavirus NSs ORFs are functional and the products inhibit activation of the interferon-beta promoter

AU - Jääskeläinen, KM

AU - Kaukinen, KM

AU - Minskaya, ES

AU - Plyusnina, A

AU - Vapalahti, O

AU - Elliott, Richard Michael

AU - Weber, F

AU - Vaheri, A

AU - Plyusnin, A

PY - 2007/10

Y1 - 2007/10

N2 - 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-beta) promoter, and nuclear factor kappa B (NF-kappa beta)- and interferon regulatory factor-3 (IRF-3) responsive promoters, were inhibited in COS-7 cells transiently expressing TULV or PUUV NSs. Also IFN-beta 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 ORE 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 lFNs.

AB - 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-beta) promoter, and nuclear factor kappa B (NF-kappa beta)- and interferon regulatory factor-3 (IRF-3) responsive promoters, were inhibited in COS-7 cells transiently expressing TULV or PUUV NSs. Also IFN-beta 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 ORE 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 lFNs.

KW - hantavirus

KW - TULV

KW - PUUV

KW - NSs ORF

KW - innate immunity

KW - IFN

KW - NONSTRUCTURAL PROTEIN NSS

KW - NUCLEOCAPSID PROTEIN

KW - ENDOTHELIAL-CELLS

KW - FEVER VIRUS

KW - NONPATHOGENIC HANTAVIRUSES

KW - HEMORRHAGIC-FEVER

KW - RNA-POLYMERASE

KW - HANTAAN VIRUS

KW - I INTERFERON

KW - MXA PROTEIN

UR - http://www.scopus.com/inward/record.url?scp=34548245061&partnerID=8YFLogxK

U2 - 10.1002/jmv.20948

DO - 10.1002/jmv.20948

M3 - Article

SN - 0146-6615

VL - 79

SP - 1527

EP - 1536

JO - Journal of Medical Virology

JF - Journal of Medical Virology

IS - 10

ER -

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

Abstract

Keywords

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