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

Published

Journal Article

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-alpha, -beta, and -gamma 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-alpha/beta receptors than in wild-type mice, suggesting that IFN-alpha/beta is important in controlling replication. In contrast, IFN-gamma 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-gamma 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.

Full Text

Duke Authors

Cited Authors

  • Aguilar, PV; Paessler, S; Carrara, A-S; Baron, S; Poast, J; Wang, E; Moncayo, AC; Anishchenko, M; Watts, D; Tesh, RB; Weaver, SC

Published Date

  • September 2005

Published In

Volume / Issue

  • 79 / 17

Start / End Page

  • 11300 - 11310

PubMed ID

  • 16103182

Pubmed Central ID

  • 16103182

Electronic International Standard Serial Number (EISSN)

  • 1098-5514

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/JVI.79.17.11300-11310.2005

Language

  • eng