Translation of unspliced retroviral genomic RNA in the host cell is regulated in both space and time

Abstract

Retroviruses carry a genomic intron-containing RNA with a long structured 5'-untranslated region, which acts either as a genome encapsidated in the viral progeny or as an mRNA encoding the key structural protein, Gag. We developed a single-molecule microscopy approach to simultaneously visualize the viral mRNA and the nascent Gag protein during translation directly in the cell. We found that a minority of the RNA molecules serve as mRNA and that they are translated in a fast and efficient process. Surprisingly, viral polysomes were also observed at the cell periphery, indicating that translation is regulated in both space and time. Virus translation near the plasma membrane may benefit from reduced competition for ribosomes with most cellular cytoplasmic mRNAs. In addition, local and efficient translation must spare energy to produce Gag proteins, where they accumulate to assemble new viral particles, potentially allowing the virus to evade the host's antiviral defenses.