Variation in interferon sensitivity and induction among strains of eastern equine encephalitis virus

Patricia Aguilar, Slobodan Paessler, Anne Sophie Carrara, Samuel Baron, Joyce Poast, Eryu Wang, Abelardo C. Moncayo, Michael Anishchenko, Douglas Watts, Robert B. Tesh, Scott Weaver

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Eastern equine encephalitis virus (EEEV) causes human encephalitis in North America (NA), but in South America (SA) it has rarely been associated with human disease, suggesting that SA strains are less virulent. To evaluate the hypothesis that this virulence difference is due to a greater ability of NA strains to evade innate immunity, we compared replication of NA and SA strains in Vero cells pretreated with interferon (IFN). Human IFN-α, -β, and -γ generally exhibited less effect on replication of NA than SA strains, supporting this hypothesis. In the murine model, no consistent difference in IFN induction was observed between NA and SA strains. After infection with most EEEV strains, higher viremia levels and shorter survival times were observed in mice deficient in IFN-α/β receptors than in wild-type mice, suggesting that IFN-α/β is important in controlling replication. In contrast, IFN-γ receptor-deficient mice infected with NA and SA strains had similar viremia levels and mortality rates to those of wild-type mice, suggesting that IFN-γ does not play a major role in murine protection. Mice pretreated with poly(I-C), a nonspecific IFN inducer, exhibited dose-dependent protection against fatal eastern equine encephalitis, further evidence that IFN is important in controlling disease. Overall, our in vivo results did not support the hypothesis that NA strains are more virulent in humans due to their greater ability to counteract the IFN response. However, further studies using a better model of human disease are needed to confirm the results of differential human IFN sensitivity obtained in our in vitro experiments.

Original languageEnglish (US)
Pages (from-to)11300-11310
Number of pages11
JournalJournal of Virology
Volume79
Issue number17
DOIs
StatePublished - Sep 2005

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Eastern equine encephalitis virus
interferons
Interferons
North America
South America
Interferon Receptors
mice
Viremia
Eastern Equine Encephalomyelitis
viremia
encephalitis
Interferon Inducers
human diseases
Vero Cells
Encephalitis
Innate Immunity
polyinosinic-polycytidylic acid
receptors
Virulence

ASJC Scopus subject areas

  • Immunology

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Variation in interferon sensitivity and induction among strains of eastern equine encephalitis virus. / Aguilar, Patricia; Paessler, Slobodan; Carrara, Anne Sophie; Baron, Samuel; Poast, Joyce; Wang, Eryu; Moncayo, Abelardo C.; Anishchenko, Michael; Watts, Douglas; Tesh, Robert B.; Weaver, Scott.

In: Journal of Virology, Vol. 79, No. 17, 09.2005, p. 11300-11310.

Research output: Contribution to journalArticle

Aguilar, P, Paessler, S, Carrara, AS, Baron, S, Poast, J, Wang, E, Moncayo, AC, Anishchenko, M, Watts, D, Tesh, RB & Weaver, S 2005, 'Variation in interferon sensitivity and induction among strains of eastern equine encephalitis virus', Journal of Virology, vol. 79, no. 17, pp. 11300-11310. https://doi.org/10.1128/JVI.79.17.11300-11310.2005
Aguilar, Patricia ; Paessler, Slobodan ; Carrara, Anne Sophie ; Baron, Samuel ; Poast, Joyce ; Wang, Eryu ; Moncayo, Abelardo C. ; Anishchenko, Michael ; Watts, Douglas ; Tesh, Robert B. ; Weaver, Scott. / Variation in interferon sensitivity and induction among strains of eastern equine encephalitis virus. In: Journal of Virology. 2005 ; Vol. 79, No. 17. pp. 11300-11310.
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