title: Partial dissociation of subgroup C phenotype and in vivo behaviour in feline leukaemia viruses with chimeric envelope genes.
abstract: Feline leukaemia viruses (FeLVs) are classified into subgroups A, B and C by their use of different host cell receptors on feline cells, a phenotype which is determined by the viral envelope. FeLV-A is the ubiquitous, highly infectious form of FeLV, and FeLV-C isolates are rare variants which are invariably isolated along with FeLV-A. The FeLV-C isolates share the capacity to induce acute non-regenerative anaemia and the prototype, FeLV-C/Sarma, has strongly age-restricted infectivity for cats. The FeLV-C/Sarma env sequence is closely related to that of common, weakly pathogenic FeLV-A isolates. We now show by construction of chimeric viruses that the receptor specificity of FeLV-A/Glasgow-1 virus can be converted to that of FeLV-C by exchange of a single env variable domain, Vr1, which differs by a three codon deletion and nine adjacent substitutions. Attempts to dissect this region further by directed mutagenesis resulted in disabled proviruses. Sequence analysis of independent natural FeLV-C isolates showed that they have unique Vr1 sequences which are distinct from the conserved FeLV-A pattern. The chimeric viruses which acquired the host range and subgroup properties of FeLV-C retained certain FeLV-A-like properties in that they were non-cytopathogenic in 3201B feline T cells and readily induced viraemia in weanling animals. They also induced a profound anaemia in neonates which had a more prolonged course than that induced by FeLV-C/Sarma and which was macrocytic rather than non-regenerative in nature. Although receptor specificity and a major determinant of pathogenicity segregate with Vr1, it appears that sequences elsewhere in the genome influence infectivity and pathogenicity independently of the subgroup phenotype.
authors.affiliation: Beatson Institute for Cancer Research, CRC Beatson Laboratories, Glasgow, U.K.
authors.forename: M A
authors.initials: MA
authors.lastname: Rigby
authors.forename: J L
authors.initials: JL
authors.lastname: Rojko
authors.forename: M A
authors.initials: MA
authors.lastname: Stewart
authors.forename: G J
authors.initials: GJ
authors.lastname: Kociba
authors.forename: C M
authors.initials: CM
authors.lastname: Cheney
authors.forename: L J
authors.initials: LJ
authors.lastname: Rezanka
authors.forename: L E
authors.initials: LE
authors.lastname: Mathes
authors.forename: J R
authors.initials: JR
authors.lastname: Hartke
authors.forename: O
authors.initials: O
authors.lastname: Jarrett
authors.forename: J C
authors.initials: JC
authors.lastname: Neil
mesh_terms: D000595:Amino Acid Sequence; D000740:Anemia / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D002371:Cat Diseases; D002415:Cats; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005814:Genes, Viral / Q000235:genetics*; D005256:Leukemia Virus, Feline / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D007942:Leukemia, Experimental / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010641:Phenotype; D011533:Proviruses / Q000235:genetics; D011991:Receptors, Virus; D011994:Recombinant Proteins / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D014759:Viral Envelope Proteins / Q000235:genetics*; D014774:Virulence
chemical_list: D011991:Receptors, Virus; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; C073723:glycoprotein gp70, Feline leukemia virus