title: Phylogenetic analysis of canine distemper virus in South America clade 1 reveals unique molecular signatures of the local epidemic.
abstract: Canine distemper virus (CDV) is a highly contagious pathogen for domestic dogs and several wild carnivore species. In Brazil, natural infection of CDV in dogs is very high due to the large non-vaccinated dog population, a scenario that calls for new studies on the molecular epidemiology. This study investigates the phylodynamics and amino-acid signatures of CDV epidemic in South America by analyzing a large dataset compiled from publicly available sequences and also by collecting new samples from Brazil. A population of 175 dogs with canine distemper (CD) signs was sampled, from which 89 were positive for CDV, generating 42 new CDV sequences. Phylogenetic analysis of the new and publicly available sequences revealed that Brazilian sequences mainly clustered in South America 1 (SA1) clade, which has its origin estimated to the late 1980's. The reconstruction of the demographic history in SA1 clade showed an epidemic expanding until the recent years, doubling in size every nine years. SA1 clade epidemic distinguished from the world CDV epidemic by the emergence of the R580Q strain, a very rare and potentially detrimental substitution in the viral genome. The R580Q substitution was estimated to have happened in one single evolutionary step in the epidemic history in SA1 clade, emerging shortly after introduction to the continent. Moreover, a high prevalence (11.9%) of the Y549H mutation was observed among the domestic dogs sampled here. This finding was associated (p<0.05) with outcome-death and higher frequency in mixed-breed dogs, the later being an indicator of a continuous exchange of CDV strains circulating among wild carnivores and domestic dogs. The results reported here highlight the diversity of the worldwide CDV epidemic and reveal local features that can be valuable for combating the disease.
authors.affiliation: Laboratório de Diagnóstico Molecular, Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil, Av. Farroupilha, 8001, 92425-900 Canoas, Rio Grande do Sul, Brazil; Hospital Veterinário, Curso de Medicina Veterinária, Universidade Luterana do Brasil, Av. Farroupilha, 8001, 92425-900 Canoas, Rio Grande do Sul, Brazil.
authors.forename: Cristine D B
authors.initials: CDB
authors.lastname: Fischer
authors.affiliation: Laboratório de Diagnóstico Molecular, Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil, Av. Farroupilha, 8001, 92425-900 Canoas, Rio Grande do Sul, Brazil. Electronic address: akograf@gmail.com.
authors.forename: Tiago
authors.initials: T
authors.lastname: Gräf
authors.affiliation: Laboratório de Diagnóstico Molecular, Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil, Av. Farroupilha, 8001, 92425-900 Canoas, Rio Grande do Sul, Brazil; Hospital Veterinário, Curso de Medicina Veterinária, Universidade Luterana do Brasil, Av. Farroupilha, 8001, 92425-900 Canoas, Rio Grande do Sul, Brazil; Simbios Biotecnologia, Rua Caí, 541, 94940-030 Cachoeirinha, Rio Grande do Sul, Brazil.
authors.forename: Nilo
authors.initials: N
authors.lastname: Ikuta
authors.affiliation: Laboratório de Diagnóstico Molecular, Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil, Av. Farroupilha, 8001, 92425-900 Canoas, Rio Grande do Sul, Brazil.
authors.forename: Fernanda K M
authors.initials: FKM
authors.lastname: Lehmann
authors.affiliation: Department of Biochemistry, Western University, London, ON N6A 5C1, Canada.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Passos
authors.affiliation: Laboratório de Diagnóstico Molecular, Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil, Av. Farroupilha, 8001, 92425-900 Canoas, Rio Grande do Sul, Brazil; Hospital Veterinário, Curso de Medicina Veterinária, Universidade Luterana do Brasil, Av. Farroupilha, 8001, 92425-900 Canoas, Rio Grande do Sul, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Makiejczuk
authors.affiliation: Laboratório de Diagnóstico Molecular, Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil, Av. Farroupilha, 8001, 92425-900 Canoas, Rio Grande do Sul, Brazil; Hospital Veterinário, Curso de Medicina Veterinária, Universidade Luterana do Brasil, Av. Farroupilha, 8001, 92425-900 Canoas, Rio Grande do Sul, Brazil.
authors.forename: Marcos A T
authors.initials: MAT
authors.lastname: Silveira
authors.affiliation: Simbios Biotecnologia, Rua Caí, 541, 94940-030 Cachoeirinha, Rio Grande do Sul, Brazil.
authors.forename: André S K
authors.initials: ASK
authors.lastname: Fonseca
authors.affiliation: Laboratório de Virologia, Faculdade de Veterinária, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9090, 91540-000 Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Cláudio W
authors.initials: CW
authors.lastname: Canal
authors.affiliation: Laboratório de Diagnóstico Molecular, Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil, Av. Farroupilha, 8001, 92425-900 Canoas, Rio Grande do Sul, Brazil; Hospital Veterinário, Curso de Medicina Veterinária, Universidade Luterana do Brasil, Av. Farroupilha, 8001, 92425-900 Canoas, Rio Grande do Sul, Brazil; Simbios Biotecnologia, Rua Caí, 541, 94940-030 Cachoeirinha, Rio Grande do Sul, Brazil.
authors.forename: Vagner R
authors.initials: VR
authors.lastname: Lunge
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001499:Bayes Theorem; D001938:Brazil / Q000453:epidemiology; D004216:Distemper / Q000453:epidemiology* / Q000635:transmission / Q000821:virology; D004217:Distemper Virus, Canine / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D004285:Dogs; D058872:Epidemics; D005260:Female; D006389:Hemagglutinins, Viral / Q000235:genetics*; D008297:Male; D017720:Molecular Epidemiology; D009154:Mutation; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics*
chemical_list: D006389:Hemagglutinins, Viral; D012367:RNA, Viral
keywords: Amino acid signature; Canine distemper virus; Molecular epidemiology; Phylogeny; South America