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Virus-Cell Interactions

Chikungunya Virus Nonstructural Protein 2 Inhibits Type I/II Interferon-Stimulated JAK-STAT Signaling

Jelke J. Fros, Wen Jun Liu, Natalie A. Prow, Corinne Geertsema, Maarten Ligtenberg, Dana L. Vanlandingham, Esther Schnettler, Just M. Vlak, Andreas Suhrbier, Alexander A. Khromykh, Gorben P. Pijlman
Jelke J. Fros
1Laboratory of Virology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, Netherlands
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Wen Jun Liu
2Australian Army Malaria Institute, Enoggera, Brisbane, QLD 4051
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Natalie A. Prow
3Centre for Infectious Disease Research, School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Brisbane, QLD 4072
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Corinne Geertsema
1Laboratory of Virology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, Netherlands
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Maarten Ligtenberg
1Laboratory of Virology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, Netherlands
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Dana L. Vanlandingham
4Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas
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Esther Schnettler
1Laboratory of Virology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, Netherlands
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Just M. Vlak
1Laboratory of Virology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, Netherlands
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Andreas Suhrbier
5Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia
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Alexander A. Khromykh
3Centre for Infectious Disease Research, School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Brisbane, QLD 4072
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Gorben P. Pijlman
1Laboratory of Virology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, Netherlands
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  • For correspondence: gorben.pijlman@wur.nl
DOI: 10.1128/JVI.00949-10
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ABSTRACT

Chikungunya virus (CHIKV) is an emerging human pathogen transmitted by mosquitoes. Like that of other alphaviruses, CHIKV replication causes general host shutoff, leading to severe cytopathicity in mammalian cells, and inhibits the ability of infected cells to respond to interferon (IFN). Recent research, however, suggests that alphaviruses may have additional mechanisms to circumvent the host's antiviral IFN response. Here we show that CHIKV replication is resistant to inhibition by interferon once RNA replication has been established and that CHIKV actively suppresses the antiviral IFN response by preventing IFN-induced gene expression. Both CHIKV infection and CHIKV replicon RNA replication efficiently blocked STAT1 phosphorylation and/or nuclear translocation in mammalian cells induced by either type I or type II IFN. Expression of individual CHIKV nonstructural proteins (nsPs) showed that nsP2 was a potent inhibitor of IFN-induced JAK-STAT signaling. In addition, mutations in CHIKV-nsP2 (P718S) and Sindbis virus (SINV)-nsP2 (P726S) that render alphavirus replicons noncytopathic significantly reduced JAK-STAT inhibition. This host shutoff-independent inhibition of IFN signaling by CHIKV is likely to have an important role in viral pathogenesis.

  • Copyright © 2010 American Society for Microbiology
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Chikungunya Virus Nonstructural Protein 2 Inhibits Type I/II Interferon-Stimulated JAK-STAT Signaling
Jelke J. Fros, Wen Jun Liu, Natalie A. Prow, Corinne Geertsema, Maarten Ligtenberg, Dana L. Vanlandingham, Esther Schnettler, Just M. Vlak, Andreas Suhrbier, Alexander A. Khromykh, Gorben P. Pijlman
Journal of Virology Sep 2010, 84 (20) 10877-10887; DOI: 10.1128/JVI.00949-10

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Chikungunya Virus Nonstructural Protein 2 Inhibits Type I/II Interferon-Stimulated JAK-STAT Signaling
Jelke J. Fros, Wen Jun Liu, Natalie A. Prow, Corinne Geertsema, Maarten Ligtenberg, Dana L. Vanlandingham, Esther Schnettler, Just M. Vlak, Andreas Suhrbier, Alexander A. Khromykh, Gorben P. Pijlman
Journal of Virology Sep 2010, 84 (20) 10877-10887; DOI: 10.1128/JVI.00949-10
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KEYWORDS

chikungunya virus
viral nonstructural proteins

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