title: Rapid evolution of the env gene leader sequence in cats naturally infected with feline immunodeficiency virus.
abstract: Analysing the evolution of feline immunodeficiency virus (FIV) at the intra-host level is important in order to address whether the diversity and composition of viral quasispecies affect disease progression. We examined the intra-host diversity and the evolutionary rates of the entire env and structural fragments of the env sequences obtained from sequential blood samples in 43 naturally infected domestic cats that displayed different clinical outcomes. We observed in the majority of cats that FIV env showed very low levels of intra-host diversity. We estimated that env evolved at a rate of 1.16×10(-3) substitutions per site per year and demonstrated that recombinant sequences evolved faster than non-recombinant sequences. It was evident that the V3-V5 fragment of FIV env displayed higher evolutionary rates in healthy cats than in those with terminal illness. Our study provided the first evidence that the leader sequence of env, rather than the V3-V5 sequence, had the highest intra-host diversity and the highest evolutionary rate of all env fragments, consistent with this region being under a strong selective pressure for genetic variation. Overall, FIV env displayed relatively low intra-host diversity and evolved slowly in naturally infected cats. The maximum evolutionary rate was observed in the leader sequence of env. Although genetic stability is not necessarily a prerequisite for clinical stability, the higher genetic stability of FIV compared with human immunodeficiency virus might explain why many naturally infected cats do not progress rapidly to AIDS.
authors.affiliation: Small Animal Hospital, University of Glasgow, Glasgow, UK.|MRC University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
authors.forename: Paweł M
authors.initials: PM
authors.lastname: Bęczkowski
authors.affiliation: MRC University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hughes
authors.affiliation: Boyd Orr Centre for Population and Ecosystem Health & Institute of Biodiversity, Animal Health & Comparative Medicine, University of Glasgow, Glasgow, UK.|MRC University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
authors.forename: Roman
authors.initials: R
authors.lastname: Biek
authors.affiliation: Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Annette
authors.initials: A
authors.lastname: Litster
authors.affiliation: MRC University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Willett
authors.affiliation: MRC University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Hosie
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002415:Cats; D015686:Gene Products, env / Q000235:genetics*; D015752:Genes, env; D014644:Genetic Variation; D016089:Immunodeficiency Virus, Feline / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny
chemical_list: D015686:Gene Products, env