Feline leukemia virus genetic variation and disease association
Description
Feline leukemia virus (FeLV) is a naturally occurring retrovirus endemic in an outbreeding mammalian species, the domestic cat. Like other retroviruses, FeLV is a genetically complex family of closely related viruses subject to selective pressures in the natural host. The variable clinical outcome of FeLV infection, thought to reflect the genetic diversity, includes degenerative diseases like anemia or immunodeficiency as well as proliferative diseases like leukemia or lymphoma. Genetic variation in the FeLV LTR and SU gene was examined in diseased tissues of naturally infected cats from two natural cohorts. In one cohort, LTRs with duplicated enhancer sequences were isolated uniformly from T-cell tumors but were rarely identified in non-T-cell diseases. In non-T-cell diseases, LTRs contained two, three or four tandemly repeated copies of a 21-bp sequence downstream of enhancer which did not vary in sequence or position in the LTR. Triplication of the 21-bp repeat was shown to confer the optimal replicative advantage in feline cells. The SU gene linked to the triplication-containing LTR was observed to differ across the receptor-determining regions to a greater extent than other natural, transmissible isolates of FeLV differ among themselves. Similar mutational changes in SU were detected in proviruses isolated from naturally occurring non-T-cell lymphomas, lymphocytic leukemia and myeloproliferative disorder. The prototype isolate of this group, termed FeLV-945, was further examined to study the biological impact of SU variation. Results demonstrated FeLV-945 SU to exhibit host range and superinfection interference properties like FeLV-A, but conferred a replicative advantage to certain feline cell types and conferred significantly more efficient binding to feline cells. Analysis of FeLV-945 in vivo indicated that the distinctive LTR and SU gene of FeLV-945 do not necessarily determine the disease spectrum from which FeLV-945 was originally isolated, but mediate a rapid pathogenesis with distinctive clinical features. Molecular analyses of DNA from FeLV-945-induced tumors indicate distinct viral and host determinants associated with the induction of T-cell and non-T-cell lymphomas