A five-amino-acid deletion of the eastern equine encephalitis virus capsid protein attenuates replication in mammalian systems but not in mosquito cells.
Eastern equine encephalitis virus (EEEV) is a human and veterinary pathogen that causes sporadic cases of fatal neurological disease. We previously demonstrated that the capsid protein of EEEV is a potent inhibitor of host cell gene expression and that this function maps to the amino terminus of the protein. We now identify amino acids 55 to 75, within the N terminus of the capsid, as critical for the inhibition of host cell gene expression. An analysis of stable EEEV replicons expressing mutant capsid proteins corroborated these mapping data. When deletions of 5 to 20 amino acids within this region of the capsid were introduced into infectious EEEV, the mutants exhibited delayed replication in Vero cells. However, the replication of the 5-amino-acid deletion mutant in C710 mosquito cells was not affected, suggesting that virus replication and assembly were affected in a cell-specific manner. Both 5- and 20-amino-acid deletion mutant viruses exhibited increased sensitivity to interferon (IFN) in cell culture and impaired replication and complete attenuation in mice. In summary, we have identified a region within the capsid protein of EEEV that contributes to the inhibition of host gene expression and to the protection of EEEV from the antiviral effects of IFNs. This region is also critical for EEEV pathogenesis.
Aguilar
Patricia V
PV
Department of Microbiology, Box 1124, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029, USA. patricia.aguilar@mssm.edu
Leung
Lawrence W
LW
Wang
Eryu
E
Weaver
Scott C
SC
Basler
Christopher F
CF
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D036022:Capsid Proteins / Q000235:genetics*; D002460:Cell Line; D002522:Chlorocebus aethiops; D009033:Culicidae; D004663:Encephalitis Virus, Eastern Equine / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D004683:Encephalomyelitis, Equine / Q000821:virology; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D051379:Mice; D017384:Sequence Deletion; D014774:Virulence; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*
D000998:Antiviral Agents; D036022:Capsid Proteins; D007372:Interferons