Unique long terminal repeat and surface glycoprotein gene sequences of feline leukemia virus as determinants of disease outcome.
The outcome of feline leukemia virus (FeLV) infection in nature is variable, including malignant, proliferative, and degenerative disorders. The determinants of disease outcome are not well understood but are thought to include viral, host, and environmental factors. In particular, genetic variations in the FeLV long terminal repeat (LTR) and SU gene have been linked to disease outcome. FeLV-945 was previously identified as a natural isolate predominant in non-T-cell neoplastic and nonneoplastic diseases in a geographic cohort. The FeLV-945 LTR was shown to contain unique repeat elements, including a 21-bp triplication downstream of the enhancer. The FeLV-945 SU gene was shown to encode mutational changes in functional domains of the protein. The present study details the outcomes of infection with recombinant FeLVs in which the LTR and envelope (env) gene of FeLV-945, or the LTR only, was substituted for homologous sequences in a horizontally transmissible prototype isolate, FeLV-A/61E. The results showed that the FeLV-945 LTR determined the kinetics of disease. Substitution of the FeLV-945 LTR into FeLV-A/61E resulted in a significantly more rapid disease onset but did not alter the tumorigenic spectrum. In contrast, substitution of both the FeLV-945 LTR and env gene changed the disease outcome entirely. Further, the impact of FeLV-945 env on the disease outcome was dependent on the route of inoculation. Since the TM genes of FeLV-945 and FeLV-A/61E are nearly identical but the SU genes differ significantly, FeLV-945 SU is implicated in the outcome. These findings identify the FeLV-945 LTR and SU gene as determinants of disease.
Chandhasin
Chandtip
C
Department of Microbiology and Immunology, Tulane University School of Medicine, 1430 Tulane Ave. SL-38, New Orleans, LA 70112, USA.
Coan
Patricia N
PN
Pandrea
Ivona
I
Grant
Chris K
CK
Lobelle-Rich
Patricia A
PA
Puetter
Adriane
A
Levy
Laura S
LS
D000818:Animals; D000831:Animals, Newborn; D002415:Cats; D004195:Disease Models, Animal; D005814:Genes, Viral; D005256:Leukemia Virus, Feline / Q000235:genetics* / Q000472:pathogenicity; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D012192:Retroviridae Infections / Q000821:virology*; D020079:Terminal Repeat Sequences; D014412:Tumor Virus Infections / Q000821:virology*; D014759:Viral Envelope Proteins / Q000235:genetics*; D014774:Virulence
D014759:Viral Envelope Proteins