Characterization of functional domains of equine infectious anemia virus Rev suggests a bipartite RNA-binding domain

Jae Hyung Lee, Scan C. Murphy, Michael A. Belshan, Wendy O. Sparks, Yvonne Wannemuehler, Sijun Liu, Thomas J. Hope, Drena Dobbs, Susan Carpenter

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Equine infectious anemia virus (EIAV) Rev is an essential regulatory protein that facilitates expression of viral mRNAs encoding structural proteins and genomic RNA and regulates alternative splicing of the bicistronic tat/rev mRNA. EIAV Rev is characterized by a high rate of genetic variation in vivo, and changes in Rev genotype and phenotype have been shown to coincide with changes in clinical disease. To better understand how genetic variation alters Rev phenotype, we undertook deletion and mutational analyses to map functional domains and to identify specific motifs that are essential for EIAV Rev activity. All functional domains are contained within the second exon of EIAV Rev. The overall organization of domains within Rev exon 2 includes a nuclear export signal, a large central region required for RNA binding, a nonessential region, and a C-terminal region required for both nuclear localization and RNA binding. Subcellular localization of green fluorescent protein-Rev mutants indicated that basic residues within the KRRRK motif in the C-terminal region of Rev are necessary for targeting of Rev to the nucleus. Two separate regions of Rev were necessary for RNA binding: a central region encompassing residues 57 to 130 and a C-terminal region spanning residues 144 to 165. Within these regions were two distinct, short arginine-rich motifs essential for RNA binding, including an RRDRW motif in the central region and the KRRRK motif near the C terminus. These findings suggest that EIAV Rev utilizes a bipartite RNA-binding domain.

Original languageEnglish
Pages (from-to)3844-3852
Number of pages9
JournalJournal of Virology
Volume80
Issue number8
DOIs
StatePublished - Apr 2006

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Equine infectious anemia virus
RNA
Exons
exons
Nuclear Export Signals
Phenotype
Nuclear RNA
Messenger RNA
Alternative Splicing
phenotype
genetic variation
Green Fluorescent Proteins
structural proteins
alternative splicing
regulatory proteins
Arginine
green fluorescent protein
Proteins
arginine
Genotype

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Characterization of functional domains of equine infectious anemia virus Rev suggests a bipartite RNA-binding domain. / Lee, Jae Hyung; Murphy, Scan C.; Belshan, Michael A.; Sparks, Wendy O.; Wannemuehler, Yvonne; Liu, Sijun; Hope, Thomas J.; Dobbs, Drena; Carpenter, Susan.

In: Journal of Virology, Vol. 80, No. 8, 04.2006, p. 3844-3852.

Research output: Contribution to journalArticle

Lee, JH, Murphy, SC, Belshan, MA, Sparks, WO, Wannemuehler, Y, Liu, S, Hope, TJ, Dobbs, D & Carpenter, S 2006, 'Characterization of functional domains of equine infectious anemia virus Rev suggests a bipartite RNA-binding domain', Journal of Virology, vol. 80, no. 8, pp. 3844-3852. https://doi.org/10.1128/JVI.80.8.3844-3852.2006
Lee, Jae Hyung ; Murphy, Scan C. ; Belshan, Michael A. ; Sparks, Wendy O. ; Wannemuehler, Yvonne ; Liu, Sijun ; Hope, Thomas J. ; Dobbs, Drena ; Carpenter, Susan. / Characterization of functional domains of equine infectious anemia virus Rev suggests a bipartite RNA-binding domain. In: Journal of Virology. 2006 ; Vol. 80, No. 8. pp. 3844-3852.
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