PMID:17267491

Citation	Aguilar, PV, Weaver, SC and Basler, CF (2007) Capsid protein of eastern equine encephalitis virus inhibits host cell gene expression. J. Virol. 81:3866-76
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.
Links	PubMed PMC1866141 Online version:10.1128/JVI.02075-06
Keywords	Capsid Proteins/immunology; Capsid Proteins/physiology; Cell Line; Chloramphenicol O-Acetyltransferase/analysis; Encephalitis Virus, Eastern Equine/immunology; Encephalitis Virus, Eastern Equine/physiology; Eukaryotic Initiation Factor-2/metabolism; Gene Expression Regulation; Genes, Reporter; Green Fluorescent Proteins/analysis; Humans; Interferon-gamma/antagonists & inhibitors; Luciferases/analysis; Phosphorylation; Protein Structure, Tertiary; RNA, Messenger/biosynthesis; Virus Replication
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
EEEV:Q66579		GO:0039653: suppression by virus of host transcription	ECO:0000314:		P		Figure 2 shows that the EEEV capsid protein is an inhibitor of gene expression.	complete CACAO 9605
EEEV:Q66579		GO:0006468: protein phosphorylation	ECO:0000314:		P		Fig. 4: 293T cells were cotransfected with luciferase reporter plasmid and either empty vector or plasmid expressing EEEV capsid/entire EEEV structural polyprotein/LaCrosse virus NSs, phophorylated eIF2a appeared most prominantly in cells expressing EEEV capsid	complete CACAO 9699
EEEV:Q66579		GO:0039501: suppression by virus of host type I interferon production	ECO:0000314:		P		Fig. 2A: cells were transfected with an IFN-beta-promoter-CAT-reporter plasmid and either an empty vector or a capsid expression plasmid, cells expressing the capsid had lower CAT levels, indicating the inhibition of IFN-beta promoter expression	complete CACAO 9928
EEEV:Q66579	involved_in	GO:0039653: suppression by virus of host transcription	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
EEEV:Q66579	involved_in	GO:0039501: suppression by virus of host type I interferon production	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
BUNLC:NSS		GO:0001934: positive regulation of protein phosphorylation	ECO:0000314:		P		Fig. 4; phosphorylated eIF2α seen in cells expressing LCV-NSs	complete CACAO 9858
BUNLC:NSS	involved_in	GO:0001934: positive regulation of protein phosphorylation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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