Partial dissociation of subgroup C phenotype and in vivo behaviour in feline leukaemia viruses with chimeric envelope genes.
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.
Rigby
M A
MA
Beatson Institute for Cancer Research, CRC Beatson Laboratories, Glasgow, U.K.
Rojko
J L
JL
Stewart
M A
MA
Kociba
G J
GJ
Cheney
C M
CM
Rezanka
L J
LJ
Mathes
L E
LE
Hartke
J R
JR
Jarrett
O
O
Neil
J C
JC
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
D011991:Receptors, Virus; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; C073723:glycoprotein gp70, Feline leukemia virus