title: Analysis of single-nucleotide polymorphisms in the APOBEC3H gene of domestic cats (Felis catus) and their association with the susceptibility to feline immunodeficiency virus and feline leukemia virus infections.
abstract: Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are widely distributed retroviruses that infect domestic cats (Felis catus). Restriction factors are proteins that have the ability to hamper retroviruses' replication and are part of the conserved mechanisms of anti-viral immunity of mammals. The APOBEC3 protein family is the most studied class of restriction factors; they are cytidine deaminases that generate hypermutations in provirus DNA during reverse transcription, thus causing hypermutations in the viral genome, hindering virus replication. One of the feline APOBEC3 genes, named APOBEC3H, encodes two proteins (APOBEC3H and APOBEC3CH). In other mammals, APOBEC3H single-nucleotide polymorphisms (SNPs) can alter the stability and cellular localization of the encoded protein, thus influencing its subcellular localization and reducing its anti-viral effect. In cats, the association of APOBEC3H SNPs with susceptibility to retroviral infections was not yet demonstrated. Therefore, this study aimed the investigation on the variability of APOBEC3H and the possible association with FIV/FeLV infections. DNA obtained from whole blood of fifty FIV- and/or FeLV-infected cats and fifty-nine FIV- and/or FeLV-uninfected cats were used as templates to amplify two different regions of the APOBEC3H, with subsequent sequencing and analysis. The first region was highly conserved among all samples, while in the second, six single-nucleotide variation points were identified. One of the SNPs, A65S (A65I), was significantly correlated with the susceptibility to FIV and/or FeLV infections. On the other hand, the haplotype analysis showed that the combination "GGGGCC" was positively correlated with the lack of FIV and/or FeLV infections. Our results indicate that, as previously shown in other mammals, variability of restriction factors may contribute to susceptibility of domestic cats to retroviral infections; however, these results should be confirmed by more extensive analysis and in vitro experiments.
authors.affiliation: Virology Laboratory, Microbiology, Immunology and Parasitology Department, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, RS CEP 90150-070, Brazil. Electronic address: fernandaluzcastro@hotmail.com.
authors.forename: Fernanda Luz
authors.initials: FL
authors.lastname: de Castro
authors.affiliation: Virology Laboratory, Microbiology, Immunology and Parasitology Department, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, RS CEP 90150-070, Brazil; Fundação Estadual de Produção e Pesquisa em Saúde (FEPPS), Centro de desenvolvimento científico e tecnológico (CDCT), Av. Ipiranga, 5400, Porto Alegre, RS CEP 91530-000, Brazil; Uniritter Laureate International Universities, Rua Orfanotrófio, 555, Porto Alegre, RS CEP 91849-440, Brazil.
authors.forename: Dennis Maletich
authors.initials: DM
authors.lastname: Junqueira
authors.affiliation: Virology Laboratory, Microbiology, Immunology and Parasitology Department, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, RS CEP 90150-070, Brazil; Fundação Estadual de Produção e Pesquisa em Saúde (FEPPS), Centro de desenvolvimento científico e tecnológico (CDCT), Av. Ipiranga, 5400, Porto Alegre, RS CEP 91530-000, Brazil.
authors.forename: Rúbia Marília
authors.initials: RM
authors.lastname: de Medeiros
authors.affiliation: Virology Laboratory, Microbiology, Immunology and Parasitology Department, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, RS CEP 90150-070, Brazil.
authors.forename: Tailene Rabello
authors.initials: TR
authors.lastname: da Silva
authors.affiliation: Virology Laboratory, Microbiology, Immunology and Parasitology Department, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, RS CEP 90150-070, Brazil.
authors.forename: Jamile Girardi
authors.initials: JG
authors.lastname: Costenaro
authors.affiliation: Virology Laboratory, Microbiology, Immunology and Parasitology Department, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, RS CEP 90150-070, Brazil.
authors.forename: Marcus Braga
authors.initials: MB
authors.lastname: Knak
authors.affiliation: Fundação Estadual de Produção e Pesquisa em Saúde (FEPPS), Centro de desenvolvimento científico e tecnológico (CDCT), Av. Ipiranga, 5400, Porto Alegre, RS CEP 91530-000, Brazil.
authors.forename: Sabrina Esteves
authors.initials: SE
authors.lastname: de Matos Almeida
authors.affiliation: Virology Laboratory, Microbiology, Immunology and Parasitology Department, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, RS CEP 90150-070, Brazil.
authors.forename: Fabrício Souza
authors.initials: FS
authors.lastname: Campos
authors.affiliation: Virology Laboratory, Microbiology, Immunology and Parasitology Department, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, RS CEP 90150-070, Brazil; Instituto de Pesquisas Veterinárias Desidério Finamor (IPVDF), Estrada Municipal do Conde, 6000, Eldorado do Sul, RS CEP 92990-000, Brazil.
authors.forename: Paulo Michel
authors.initials: PM
authors.lastname: Roehe
authors.affiliation: Virology Laboratory, Microbiology, Immunology and Parasitology Department, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, RS CEP 90150-070, Brazil.
authors.forename: Ana Cláudia
authors.initials: AC
authors.lastname: Franco
mesh_terms: D000483:Alleles; D000619:Aminohydrolases / Q000235:genetics*; D000818:Animals; D002371:Cat Diseases / Q000235:genetics* / Q000821:virology*; D002415:Cats; D005787:Gene Frequency; D023061:Gene Order; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D016089:Immunodeficiency Virus, Feline; D005256:Leukemia Virus, Feline; D020641:Polymorphism, Single Nucleotide; D012192:Retroviridae Infections / Q000662:veterinary*
chemical_list: D000619:Aminohydrolases
keywords: APOBEC3H; Cats; FELV; FIV; Felis catus; Polymorphisms