title: The Merkel cell polyomavirus minor capsid protein.
abstract: The surface of polyomavirus virions is composed of pentameric knobs of the major capsid protein, VP1. In previously studied polyomavirus species, such as SV40, two interior capsid proteins, VP2 and VP3, emerge from the virion to play important roles during the infectious entry process. Translation of the VP3 protein initiates at a highly conserved Met-Ala-Leu motif within the VP2 open reading frame. Phylogenetic analyses indicate that Merkel cell polyomavirus (MCV or MCPyV) is a member of a divergent clade of polyomaviruses that lack the conserved VP3 N-terminal motif. Consistent with this observation, we show that VP3 is not detectable in MCV-infected cells, VP3 is not found in native MCV virions, and mutation of possible alternative VP3-initiating methionine codons did not significantly affect MCV infectivity in culture. In contrast, VP2 knockout resulted in a >100-fold decrease in native MCV infectivity, despite normal virion assembly, viral DNA packaging, and cell attachment. Although pseudovirus-based experiments confirmed that VP2 plays an essential role for infection of some cell lines, other cell lines were readily transduced by pseudovirions lacking VP2. In cell lines where VP2 was needed for efficient infectious entry, the presence of a conserved myristoyl modification on the N-terminus of VP2 was important for its function. The results show that a single minor capsid protein, VP2, facilitates a post-attachment stage of MCV infectious entry into some, but not all, cell types.
authors.affiliation: Tumor Virus Molecular Biology Section, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Schowalter
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Buck
mesh_terms: D020816:Amino Acid Motifs; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D054878:Lipoylation / Q000235:genetics; D059965:Merkel cell polyomavirus / Q000502:physiology*; D010802:Phylogeny; D027601:Polyomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017434:Protein Structure, Tertiary; D014412:Tumor Virus Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019065:Virus Assembly / Q000502:physiology*; D053585:Virus Attachment
chemical_list: D036022:Capsid Proteins; D004279:DNA, Viral; C442543:VP2 protein, Polyomavirus; C442542:VP3 protein, Poliovirus