Towards new structural insights into the process of Poliovirus RNA translocation upon infection

Poliovirus is not only a significant human pathogen but also serves as a well-characterized model system for understanding how nonenveloped viruses infect cells. Upon binding to its receptor at the membrane of human macrophages, Poliovirus undergoes an irreversible conformational change that leads to penetration of the host cell membrane. Thereafter, it translocates its single stranded RNA genome through a self-induced pore into its host cytoplasm. The emptied nucleocapsid remains outside of the infected cell, which is then taken over by the viral replication machinery. The icosahedral Poliovirus nucleocapsid is composed of 60 copies each of four coat proteins, VP1, VP2, VP3 and VP4. The virion surface is dominated by two structural features: star-shaped mesas at the five­ fold axes and three-bladed propellers at the threefold axes. Upon binding to its receptor, the so-called 135S cell entry intermediate is formed, which involves a major conformational rearrangement that results in the externalization of VP4 and the N-terminus of VP1. Both, VP4 and VP1 are discussed to be involved in channel formation allowing the translocation of the viral RNA (TOSTESON AND CHOW, 1997). The Nterminus of VP1 resembles an amphipatic a-helix that is known to tether the particles to membranes. Several copies of this helix are believed to form the pore that allows the passage of the RNA. The contribution of VP4 remains poorly understood. Very recently the structure of the 135S particle was reported by reconstructing it from cryo-electron microscopy data (BUBECK et al., 2005). The externalization site for the N-terminus of VP1 was located near the propellers at the threefold axes. This was a surprising finding since it was believed that VP1 would be externalized at the fivefold axis, so that five VP1 helices could form the pore that clears the way for the RNA which is believed to leave the virus particle through an opening at the fivefold axis. Bubeck et al. suggest a new model in which VP4 constitutes the RNA-conducting channel whereas the N-terminus of VP1 acts either as a membrane anchor or acts in concert with VP4. Clearly there is a demand for a better understanding of the exact process of RNA translocation during Poliovirus infection.