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Rabbit Hemorrhagic Disease Virus (RHDV)capsid protein
Structural highlights
FunctionPOLG_RHDVA NTPase presumably plays a role in replication. Viral genome-linked protein is covalently linked to the 5'-end of the positive-strand, negative-strand genomic RNAs and subgenomic RNA. Acts as a genome-linked replication primer. May recruit ribosome to viral RNA thereby promoting viral proteins translation (By similarity). 3C-like protease processes the polyprotein: 3CLpro-RdRp (p72) is first released by autocleavage, then all other proteins are cleaved. RNA-directed RNA polymerase replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This sgRNA codes for structural proteins. Catalyzes the covalent attachment VPg with viral RNAs (By similarity).[PROSITE-ProRule:PRU00539] Capsid protein VP60 self assembles to form an icosahedral capsid with a T=3 symmetry, about 35 nm in diameter, and consisting of 180 capsid proteins. A smaller form of capsid with a diameter of 23 nm might be capsid proteins assembled as icosahedron with T=1 symmetry. The capsid encapsulate VP2 proteins and genomic or subgenomic RNA. Attaches virion to target cells by binding histo-blood group antigens, inducing endocytosis of the viral particle. Acidification of the endosome induces conformational change of capsid protein thereby injecting virus genomic RNA into host cytoplasm (By similarity). Publication Abstract from PubMedViruses need only one or a few structural capsid proteins to build an infectious particle. This is possible through the extensive use of symmetry and the conformational polymorphism of the structural proteins. Using virus-like particles (VLP) from rabbit hemorrhagic disease virus (RHDV) as a model, we addressed the basis of calicivirus capsid assembly and their application in vaccine design. The RHDV capsid is based on a T=3 lattice containing 180 identical subunits (VP1). We determined the structure of RHDV VLP to 8.0 A resolution by three-dimensional cryo-electron microscopy; in addition, we used San Miguel sea lion virus (SMSV) and feline calicivirus (FCV) capsid subunit structures to establish the backbone structure of VP1 by homology modeling and flexible docking analysis. Based on the three-domain VP1 model, several insertion mutants were designed to validate the VP1 pseudo-atomic model, and foreign epitopes were placed at the N- or C-terminal ends, as well as in an exposed loop on the capsid surface. We selected a set of T and B cell epitopes of varying length derived from viral and eukaryotic origins. Structural analysis of these chimeric capsids further validates the VP1 model to design new chimeras. Whereas most insertions are well tolerated, VP1 with an FCV capsid protein-neutralizing epitope at the N-terminus assembled into mixtures of T=3 and larger T=4 capsids. The calicivirus capsid protein, and perhaps that of many other viruses, can thus encode polymorphism modulators that are not anticipated from the plane sequence, with important implications for understanding virus assembly and evolution. Epitope insertion at the N-terminal molecular switch of the rabbit hemorrhagic disease virus T=3 capsid protein leads to larger T=4 capsids.,Luque D, Gonzalez JM, Gomez-Blanco J, Marabini R, Chichon J, Mena I, Angulo I, Carrascosa JL, Verdaguer N, Trus BL, Barcena J, Caston JR J Virol. 2012 Apr 4. PMID:22491457[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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