Capsid protein of eastern equine encephalitis virus inhibits host cell gene expression

Patricia Aguilar, Scott Weaver, Christopher F. Basler

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Eastern equine encephalitis virus (EEEV) causes sporadic but often severe cases of human and equine neurological disease in North America. To determine how EEEV may evade innate immune responses, we screened individual EEEV proteins for the ability to rescue the growth of a Newcastle disease virus expressing green fluorescent protein (NDV-GFP) from the antiviral effects of interferon (IFN). Only expression of the EEEV capsid facilitated NDV-GFP replication. Inhibition of the antiviral effects of IFN by the capsid appears to occur through a general inhibition of cellular gene expression. For example, the capsid inhibited the expression of several reporter genes under the control of RNA polymerase II promoters. In contrast, capsid did not inhibit expression from a T7 RNA polymerase promoter construct, suggesting that the inhibition of gene expression is specific and is not a simple manifestation of toxicity. The inhibition correlated both with capsid-induced phosphorylation of eukaryotic initiation factor 2 alpha and with capsid-mediated inhibition of cellular mRNA accumulation. Mapping analysis identified the N terminus as the region important for the inhibition of host gene expression, suggesting that this inhibition is independent of capsid protease activity. Finally, when cell lines containing EEEV replicons encoding capsid were selected, replicons consistently acquired mutations that deleted all or part of the capsid, for example, amino acids 18 to 135. Given that the amino terminus of the capsid is required to inhibit host cell gene expression, these data suggest that capsid expression from the replicons is ultimately toxic to host cells, presumably because of its ability to inhibit gene expression.

Original languageEnglish (US)
Pages (from-to)3866-3876
Number of pages11
JournalJournal of Virology
Volume81
Issue number8
DOIs
StatePublished - Apr 2007

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Eastern equine encephalitis virus
capsid
Capsid
Capsid Proteins
coat proteins
Gene Expression
gene expression
cells
replicon
Replicon
Newcastle disease virus
interferons
DNA-directed RNA polymerase
Green Fluorescent Proteins
green fluorescent protein
Interferons
Antiviral Agents
Eukaryotic Initiation Factor-2
promoter regions
Horse Diseases

ASJC Scopus subject areas

  • Immunology

Cite this

Capsid protein of eastern equine encephalitis virus inhibits host cell gene expression. / Aguilar, Patricia; Weaver, Scott; Basler, Christopher F.

In: Journal of Virology, Vol. 81, No. 8, 04.2007, p. 3866-3876.

Research output: Contribution to journalArticle

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