Uncoating of human rhinoviruses

Abstract

Human rhinoviruses (HRVs) are a major cause of the common cold. The more than one hundred serotypes, divided into species HRV-A and HRV-B, either bind intercellular adhesion molecule 1 (major group viruses) or members of the low-density lipoprotein receptor (minor group viruses) for cell entry. Some major group HRVs can also access the host cell via heparan sulphate proteoglycans. The cell attachment protein(s) of the recently discovered phylogenetic clade HRV-C is unknown. The respective receptors direct virus uptake via clathrin-dependent or independent endocytosis or via macropinocytosis. Triggered by ICAM-1 and/or the low pH environment in endosomes the virions undergo conformational alterations giving rise to hydrophobic subviral particles. These are handed over from the receptors to the endosomal membrane. According to the current view, the RNA genome is released through an opening at one of the fivefold axes of the icosahedral capsid and crosses the membrane through a pore presumably formed by viral proteins. Alternatively, the membrane may be ruptured allowing subviral particles and RNA to enter the cytosol. Whether a channel is formed or the membrane is disrupted most probably depends on the respective HRV receptor.

Lysosomal cell death at a glance

“…Adenovirus membrane lytic protein VI ruptures the membrane by causing membrane curvature stress (Maier et al, 2010;Wiethoff et al, 2005), but membrane rupture can also be caused by vesicular swelling beyond the retaining capacity of the membrane. Alternatively, viral capsid proteins of HRV2 and poliovirus insert directly into the endolysosomal membrane and form size-selective pores (Fuchs and Blaas, 2010;Tosteson and Chow, 1997). By contrast, parvovirus H-1 induces lethal LMP in glioma cells that is not directly related to the viral entry process but instead results from a dramatic downregulation of cytosolic cysteine cathepsin inhibitors, which sensitizes the cells to otherwise non-lethal cathepsin release (Di Piazza et al, 2007).…”

Coxsackievirus A9 Infects Cells via Nonacidic Multivesicular Bodies

“…After arrival in the endosome lumen, viruses can be, for example, exposed to changes in pH and ions and proteolytic events that may initiate the uncoating process (11,12). These events trigger changes in the virus particle that lead to the delivery of the genome into the cell for further replication.…”

Virus entry at a glance

“…In some cases, such as polyoma and adenoviruses, disassembly of the particle already begins before penetration into the cytosol (reviewed by Cerqueira and Schelhaas, 2012;Suomalainen and Greber, 2013). In the case of picornaviruses, uncoating is an integral part of penetration, as the viral RNA enters into the cytosol leaving the capsid behind in the endosome (reviewed by Fuchs and Blaas, 2010).…”