title: Simultaneous mutations in CA and Vif of Maedi-Visna virus cause attenuated replication in macrophages and reduced infectivity in vivo.
abstract: Maedi-visna virus (MVV) is a lentivirus of sheep sharing several key features with the primate lentiviruses. The virus causes slowly progressive diseases, mainly in the lungs and the central nervous system of sheep. Here, we investigate the molecular basis for the differential growth phenotypes of two MVV isolates. One of the isolates, KV1772, replicates well in a number of cell lines and is highly pathogenic in sheep. The second isolate, KS1, no longer grows on macrophages or causes disease. The two virus isolates differ by 129 nucleotide substitutions and two deletions of 3 and 15 nucleotides in the env gene. To determine the molecular nature of the lesions responsible for the restrictive growth phenotype, chimeric viruses were constructed and used to map the phenotype. An L120R mutation in the CA domain, together with a P205S mutation in Vif (but neither alone), could fully convert KV1772 to the restrictive growth phenotype. These results suggest a functional interaction between CA and Vif in MVV replication, a property that may relate to the innate antiretroviral defense mechanisms in sheep.
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur v/Vesturlandsveg, 112 Reykjavík, Iceland.
authors.forename: Bjarki
authors.initials: B
authors.lastname: Gudmundsson
authors.forename: Stefán Ragnar
authors.initials: SR
authors.lastname: Jónsson
authors.forename: Oddur
authors.initials: O
authors.lastname: Olafsson
authors.forename: Gudrún
authors.initials: G
authors.lastname: Agnarsdóttir
authors.forename: Sigrídur
authors.initials: S
authors.lastname: Matthíasdóttir
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Georgsson
authors.forename: Sigurbjorg
authors.initials: S
authors.lastname: Torsteinsdóttir
authors.forename: Vilhjálmur
authors.initials: V
authors.lastname: Svansson
authors.forename: Helga Bryndís
authors.initials: HB
authors.lastname: Kristbjornsdóttir
authors.forename: Sigrídur Rut
authors.initials: SR
authors.lastname: Franzdóttir
authors.forename: Olafur S
authors.initials: OS
authors.lastname: Andrésson
authors.forename: Valgerdur
authors.initials: V
authors.lastname: Andrésdóttir
mesh_terms: D000818:Animals; D004279:DNA, Viral / Q000032:analysis; D016346:Gene Products, vif / Q000235:genetics / Q000502:physiology*; D016679:Genome, Viral; D008264:Macrophages / Q000821:virology*; D009154:Mutation; D012756:Sheep; D012757:Sheep Diseases / Q000821:virology; D014779:Virus Replication; D014790:Visna-maedi virus / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D004279:DNA, Viral; D016346:Gene Products, vif