title: Hepatitis C virus F protein sequence reveals a lack of functional constraints and a variable pattern of amino acid substitution.
abstract: Hepatitis C virus (HCV) is an important human pathogen that affects 170 million people worldwide. The HCV genome is an RNA molecule that is approximately 9.6 kb in length and encodes a polyprotein that is cleaved proteolytically to generate at least 10 mature viral proteins. Recently, a new HCV protein named F has been described, which is synthesized as a result of a ribosomal frameshift. Little is known about the biological properties of this protein, but the possibility that the F protein may participate in HCV morphology or replication has been raised. In this work, the presence of functional constraints in the F protein was investigated. It was found that the rate of amino acid substitutions along the F protein was significantly higher than the rate of synonymous substitutions, and comparisons involving genes that represented independent phylogenetic lineages yielded very different divergence/conservation patterns. The distribution of stop codons in the F protein across all HCV genotypes was also investigated; genotypes 2 and 3 were found to have more stop codons than genotype 1. The results of this work suggest strongly that the pattern of divergence in the F protein is not affected by functional constraints.
authors.affiliation: Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Iguá 4225, 11400 Montevideo, Uruguay.
authors.forename: Juan
authors.initials: J
authors.lastname: Cristina
authors.affiliation: Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Iguá 4225, 11400 Montevideo, Uruguay.
authors.forename: Fernando
authors.initials: F
authors.lastname: Lopez
authors.affiliation: Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Iguá 4225, 11400 Montevideo, Uruguay.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Moratorio
authors.affiliation: Cátedra de Hemoterapia, Facultad de Medicina, Av. Italia s/n, Montevideo, Uruguay.|Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Iguá 4225, 11400 Montevideo, Uruguay.
authors.forename: Lilia
authors.initials: L
authors.lastname: López
authors.affiliation: Instituto de Investigaciones Clínicas, Facultad de Medicina 'San Fernando', Universidad Nacional Mayor de San Marcos, Parque de la Medicina, Avenida Grau Cuadra 13 s/n, Lima 01, Peru.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vasquez
authors.affiliation: Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Iguá 4225, 11400 Montevideo, Uruguay.
authors.forename: Laura
authors.initials: L
authors.lastname: García-Aguirre
authors.affiliation: Servicio de Inmunología, Hospital Nacional Edgardo Rebagliati Martins HNERN, Domingo Cueto s/n, Jesús María, Lima 11, Peru.
authors.forename: Ausberto
authors.initials: A
authors.lastname: Chunga
mesh_terms: D019943:Amino Acid Substitution; D003001:Cloning, Molecular; D018388:Codon, Terminator; D018965:Frameshifting, Ribosomal; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics*; D008969:Molecular Sequence Data; D014758:Viral Core Proteins / Q000235:genetics*; D014779:Virus Replication
chemical_list: D018388:Codon, Terminator; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus