A Novel, Fully Spliced, Accessory Gene in Equine Lentivirus with Distinct Rev-Responsive Element

Abstract

In lentiviruses, the nuclear export of viral transcripts is an important step in controlling viral gene expression. Generally, the unspliced and incompletely spliced transcripts are exported via the CRM1-dependent export pathway in a process mediated by the viral Rev protein by binding to the Rev-responsive element (RRE) located within the Env-coding region.

Identification of a Novel Post-transcriptional Transactivator from the Equine Infectious Anemia Virus

“…Recently, we confirmed the existence of two independent Rev-responsive elements (RRE) in EIAV, namely, RRE-1, located in the Env-coding region, and RRE-2, located in the Gag-coding region ( 23 ). Rev binds to RRE-1 to mediate the expression of Gag/Pol and to RRE-2 to mediate the expression of the viral protein Mat.…”

“…In our previous study ( 23 ), multiple EIAV-specific transcripts were detected from EIAV-infected horse tissue by using the reverse transcriptase-PCR (RT-PCR) ( Fig. 1A ).…”

“…In addition to the three structural proteins (Gag, Pol, and Env) shared by lentiviruses, EIAV encodes two regulatory proteins (Tat and Rev) and one accessory protein (S2). In addition, our lab recently discovered a novel viral protein Mat in EIAV ( 23 ), but the biological function of the Mat is as yet unclear. The primate lentiviruses, such as human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), encode two regulatory proteins (Tat and Rev) and four accessory proteins (Nef, Vpu, Vif, and Vpr/Vpx) ( 24 ).…”

“…Rev is translated from a fully spliced bicistronic mRNA transcript, in which the other protein encoded is Tat ( 27 ). We recently discovered multiple novel transcripts in EIAV, one of which encodes Mat ( 23 ). Interestingly, the expression of Mat depends on the Rev/CRM1-mediated nuclear export pathway, and EIAV Rev could specifically bind to the first exon of mat mRNA to promote its nuclear export.…”

“…Therefore, there must be two RREs in EIAV. The first RRE (RRE-1) is located in the Env-coding region and is responsible for the expression of viral structural proteins ( 34 – 36 ), and the second (RRE-2) overlaps with the first exon of mat mRNA located in the Gag-coding region and is responsible for the expression of Mat ( 23 ). In this study, we identified another novel transcript in EIAV containing a 303-bp open reading frame (ORF) consisting of two exons.…”