title: Budding of alphaviruses.
abstract: Alphaviruses are small highly ordered enveloped RNA viruses, which replicate very efficiently in the infected cell. They consist of a nucleocapsid (NC) and a surrounding membrane with glycoproteins. In the NC the positive single stranded RNA genome of the virus is enclosed by a T=4 icosahedral shell of capsid (C) proteins. The glycoproteins form a second shell with corresponding symmetry on the outside of the lipid membrane. These viruses mature by budding at the plasma membrane (PM) of the infected cell and enter into new cells by acid-triggered membrane fusion in endosomes. The viral glycoprotein consists of two subunits, E1, which carries the membrane fusion function, and E2, which suppresses this function until acid activation occurs. In the infected cell the RNA replication and transcription are confined to the cytoplasmic surface of endosome-derived vesicles called cytopathic vacuoles type I (CPV I). These structures are closely associated with membranes of the endoplasmic reticulum (ER), thereby creating a microenvironment for synthesis of viral proteins, assembly of the glycoproteins and formation of genome-C complexes. The budding process of the virus is initiated by C-glycoprotein interactions, possibly already before the glycoproteins arrive at the PM. This might involve a premade, ordered NC or a less ordered form of the genome-C complex. In the latter case, the interactions in the glycoprotein shell provide the major driving force for budding. The nature of the C-glycoprotein interaction has been resolved at atomic resolution by modelling. It involves hydrophobic interactions between a Tyr-X-Leu tripeptide in the internal tail of the E2 subunit and a pocket on the surface of the C protein. When the virus enters the endosome of a new cell the acid conditions trigger rearrangements in the glycoprotein shell, which result in the dissociation of the interactions that drive budding and a concomitant activation of the membrane fusion function in the E1 subunit.
authors.affiliation: Department of Biosciences at Novum, Karolinska Institute, S-141 57 Huddinge, Sweden. henrik.garoff@cbt.ki.se
authors.forename: Henrik
authors.initials: H
authors.lastname: Garoff
authors.forename: Mathilda
authors.initials: M
authors.lastname: Sjöberg
authors.forename: R Holland
authors.initials: RH
authors.lastname: Cheng
mesh_terms: D000524:Alphavirus / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002213:Capsid / Q000502:physiology*; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly / Q000502:physiology*
chemical_list: D014758:Viral Core Proteins; D014759:Viral Envelope Proteins