Retroviruses assemble new virus particles that are released by budding from the plasma membranes of infected cells. Gag proteins, encoded by retroviruses, orchestrate the assembly of virus particles in close collaboration with host cell machinery. The earliest steps in retrovirus assembly-those immediately following synthesis of Gag on cytosolic ribosomes-are poorly understood. Rous sarcoma virus (RSV) offers a unique model system for dissecting these early steps because the RSV Gag protein undergoes transient nuclear trafficking prior to plasma membrane transport. Other Gag proteins, including those of human immunodeficiency virus (HIV), murine leukemia virus (MLV), foamy virus and retrotransposons in Schizosaccharomyces pombe and Drosophila, have also been detected in the nucleus, suggesting that nuclear trafficking of Gag proteins is a common property of retroviruses and retrotransposons. In addition to retroviruses, many structural proteins of unrelated viruses, including influenza M1, NEP and NP proteins,38 Borna disease virus N and P proteins28,56 and coronavirus N protein,23,57 undergo nuclear localization and bind viral RNAs to form viral ribonuclear protein (RNP) complexes that are exported from the nucleus for packaging into virus particles. Similarly, nuclear trafficking of the RSV Gag protein is required for efficient encapsidation of the viral genomic RNA (gRNA) into assembling virus particles.19 Recently, we reported that the viral RNA itself appears to be a key factor in controlling the nucleus/cytosol distribution of RSV Gag.22 Our data demonstrate that binding of RSV RNA to the Gag protein promotes Gag-CRM1-RanGTP binding, resulting in export of the retroviral RNP from the nucleus. We propose that association of the viral RNA induces a conformational change in Gag that reveals its nuclear export signal (NES) and prepares that complex for its journey to the plasma membrane for budding. This work challenges existing dogmas regarding the molecular basis of Gagmediated selection of gRNA for packaging and may lead to novel paradigms for the mechanism of retroviral genome encapsidation.
All Science Journal Classification (ASJC) codes
- Cell Biology