Hypervariable domain of eastern equine encephalitis virus nsP3 redundantly utilizes multiple cellular proteins for replication complex assembly

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

17 Scopus Citations
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Author(s)

  • Ilya Frolov
  • Dal Young Kim
  • Maryna Akhrymuk
  • James A. Mobley
  • Elena I. Frolova

Detail(s)

Original languageEnglish
Article numbere00371-17
Journal / PublicationJournal of Virology
Volume91
Issue number14
Online published3 May 2017
Publication statusPublished - Jul 2017
Externally publishedYes

Abstract

Eastern equine encephalitis virus (EEEV) is a representative member of the New World alphaviruses. It is pathogenic for a variety of vertebrate hosts, in which EEEV induces a highly debilitating disease, and the outcomes are frequently lethal. Despite a significant public health threat, the molecular mechanism of EEEV replication and interaction with hosts is poorly understood. Our previously published data and those of other teams have demonstrated that hypervariable domains (HVDs) of the alphavirus nsP3 protein interact with virus-specific host factors and play critical roles in assembly of viral replication complexes (vRCs). The most abundantly represented HVD-binding proteins are the FXR and G3BP family members. FXR proteins drive the assembly of vRCs of Venezuelan equine encephalitis virus (VEEV), and G3BPs were shown to function in vRC assembly in the replication of chikungunya and Sindbis viruses. Our new study demonstrates that EEEV exhibits a unique level of redundancy in the use of host factors in RNA replication. EEEV efficiently utilizes both the VEEV-specific FXR protein family and the Old World alphavirusspecific G3BP protein family. A lack of interaction with either FXRs or G3BPs does not affect vRC formation; however, removal of EEEV's ability to interact with both protein families has a deleterious effect on virus growth. Other identified EEEV nsP3 HVDinteracting host proteins are also capable of supporting EEEV replication, albeit with a dramatically lower efficiency. The ability to use a wide range of host factors with redundant functions in vRC assembly and function provides a plausible explanation for the efficient replication of EEEV and may contribute to its highly pathogenic phenotype.

Research Area(s)

  • Chikungunya virus, Eastern equine encephalitis virus, FMR1, FXR1, FXR2, G3BP1, G3BP2, NsP3, Replication complex, Virus-host interactions

Citation Format(s)

Hypervariable domain of eastern equine encephalitis virus nsP3 redundantly utilizes multiple cellular proteins for replication complex assembly. / Frolov, Ilya; Kim, Dal Young; Akhrymuk, Maryna; Mobley, James A.; Frolova, Elena I.

In: Journal of Virology, Vol. 91, No. 14, e00371-17, 07.2017.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal