title: Genetic and structural analysis of Merkel cell polyomavirus large T antigen from diverse biological samples.
abstract: Merkel cell polyomavirus (MCPyV) large T antigen (LT-ag) is frequently found truncated in Merkel cell carcinomas (MCC) and it is considered a major tumor-specific signature. Nonetheless, the biological role of LT-ag nontruncated mutations is largely unknown. In this study, MCPyV LT-ag second exon from 11 non-MCC oral samples and NCBI sequences derived from different anatomical sites were studied from the genetic and structural standpoint. As expected, the LT-ag mutation profile was influenced by the geographical origin of the sample, although nonsynonymous mutations were more frequent in lesional tissues. Our in silico study suggests that the mutations found would not significantly affect protein functions, regardless of sample category. This work presents a thorough investigation of the structural and functional properties of LT-ag nontruncated mutations in MCPyV. Our results sustain the geographical influence of the MCPyV genetic profile, but do not discard genetic tissue specificities. Further investigation involving other genetic segments in healthy and lesional tissues are necessary to improve our knowledge on MCPyV pathogenesis.
authors.affiliation: Department of Microbiology and Parasitology, Universidade Federal Fluminense, Niteroi, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Freze Baez
authors.forename: Nuria
authors.initials: N
authors.lastname: Cirauqui Diaz
authors.forename: Silvia Maria
authors.initials: SM
authors.lastname: Baeta Cavalcanti
authors.forename: Rafael
authors.initials: R
authors.lastname: Brandão Varella
mesh_terms: D000952:Antigens, Polyomavirus Transforming / Q000235:genetics* / Q000276:immunology*; D001483:Base Sequence; D015266:Carcinoma, Merkel Cell / Q000821:virology*; D003198:Computer Simulation; D005091:Exons / Q000235:genetics; D006801:Humans; D059965:Merkel cell polyomavirus / Q000276:immunology*; D056004:Molecular Dynamics Simulation; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D009154:Mutation; D017434:Protein Structure, Tertiary; D012463:Saliva / Q000821:virology; D017422:Sequence Analysis, DNA; D012867:Skin / Q000821:virology; D012878:Skin Neoplasms / Q000821:virology*
chemical_list: D000952:Antigens, Polyomavirus Transforming; D050505:Mutant Proteins