title: Subtle mutational changes in the SU protein of a natural feline leukemia virus subgroup A isolate alter disease spectrum.
abstract: FeLV-945 is a representative isolate of the natural feline leukemia virus (FeLV) variant predominant in non-T-cell malignant, proliferative, and degenerative diseases in a geographic cohort. The FeLV-945 surface glycoprotein (SU) is closely related to natural horizontally transmissible FeLV subgroup A (FeLV-A) but was found to differ from a prototype to a larger extent than the members of FeLV-A differ among themselves. The sequence differences included point mutations restricted largely to the functional domains of SU, i.e., VRA, VRB, and PRR. Despite the sequence differences in these critical domains, measurements of receptor utilization, including host range and superinfection interference, confirmed the assignment of FeLV-945 to subgroup A. Other proviruses isolated from the cohort contained similar sequence hallmarks and were assigned to FeLV subgroup A. A provirus from cat 1046 contained a histidine-to-proline change at SU residue 6 within an SPHQ motif that was previously identified as a critical mediator of fusion events during virus entry. The 1046 pseudotype virus entered cells only in the presence of the soluble cofactor FeLIX provided in trans, but it retained an ecotropic host range even in the presence of FeLIX. The mutational changes in FeLV-945 were shown to confer significant functional differences compared to prototype FeLV-A viruses. The substitution of FeLV-945 envelope gene sequences for FeLV-A/61E sequences conferred a small but statistically significant replicative advantage in some feline cells. Moreover, substitution of the unique FeLV-945 long terminal repeat and envelope gene for those of FeLV-A/61E altered the disease spectrum entirely, from a thymic lymphoma of a T-cell origin to an as yet uncharacterized multicentric lymphoma that did not contain T cells.
authors.affiliation: Department of Microbiology and Immunology, Tulane University School of Medicine, 1430 Tulane Ave. SL-38, New Orleans, LA 70112, USA.
authors.forename: Chandtip
authors.initials: C
authors.lastname: Chandhasin
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Coan
authors.forename: Laura S
authors.initials: LS
authors.lastname: Levy
mesh_terms: D000818:Animals; D002371:Cat Diseases / Q000503:physiopathology / Q000821:virology; D002415:Cats; D002460:Cell Line; D004285:Dogs; D005260:Female; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D005256:Leukemia Virus, Feline / Q000235:genetics / Q000472:pathogenicity*; D008223:Lymphoma / Q000503:physiopathology / Q000821:virology; D016399:Lymphoma, T-Cell / Q000503:physiopathology / Q000821:virology; D008969:Molecular Sequence Data; D009154:Mutation; D012192:Retroviridae Infections / Q000503:physiopathology* / Q000821:virology; D017422:Sequence Analysis, DNA; D013950:Thymus Gland / Q000821:virology; D013953:Thymus Neoplasms / Q000503:physiopathology / Q000821:virology; D014412:Tumor Virus Infections / Q000503:physiopathology* / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D014759:Viral Envelope Proteins