Destiny of Unspliced Retroviral RNA: Ribosome and/or Virion?

Abstract

Retroviruses are a unique family of RNA viruses that utilize virally encoded reverse transcriptase (RT) to replicate genomic RNA through a proviral DNA intermediate (40). The provirus is permanently integrated into the host cell chromosome and, like a cellular gene, is expressed by the host cell transcription, RNA processing, and translation machinery. The primary transcription product interacts with the cellular RNA processing machinery and, similar to a typical cellular pre-mRNA, is spliced, exported to the cytoplasm, and translated by the host protein synthesis machinery. A proportion of the pre-mRNA subverts typical RNA processing and interacts with viral and/or cellular nucleocytoplasmic shuttle proteins that activate nuclear export, despite the lack of intron removal (8). In the cytoplasm, the unspliced genome-length RNA serves two essential roles. The immediate function is to serve as an mRNA template for translation of viral proteins. Another function is to serve as a genomic RNA that is packaged into assembling virions. The Gag polyprotein facilitates the specific packaging of two copies of the unspliced genome-length RNA. The nucleocapsid domain of Gag contains redundant Cys-X₂-Cys-X₄-His-X₄-Cys motifs that interact with the highly structured packaging signal (ψ or E), which is located in the 5′ untranslated region (UTR) (34a).