title: Dominance of highly divergent feline leukemia virus A progeny variants in a cat with recurrent viremia and fatal lymphoma.
abstract: BACKGROUND
  In a cat that had ostensibly recovered from feline leukemia virus (FeLV) infection, we observed the reappearance of the virus and the development of fatal lymphoma 8.5 years after the initial experimental exposure to FeLV-A/Glasgow-1. The goals of the present study were to investigate this FeLV reoccurrence and molecularly characterize the progeny viruses.
  
  
  RESULTS
  The FeLV reoccurrence was detected by the presence of FeLV antigen and RNA in the blood and saliva. The cat was feline immunodeficiency virus positive and showed CD4+ T-cell depletion, severe leukopenia, anemia and a multicentric monoclonal B-cell lymphoma. FeLV-A, but not -B or -C, was detectable. Sequencing of the envelope gene revealed three FeLV variants that were highly divergent from the virus that was originally inoculated (89-91% identity to FeLV-A/Glasgow-1). In the long terminal repeat 31 point mutations, some previously described in cats with lymphomas, were detected. The FeLV variant tissue provirus and viral RNA loads were significantly higher than the FeLV-A/Glasgow-1 loads. Moreover, the variant loads were significantly higher in lymphoma positive compared to lymphoma negative tissues. An increase in the variant provirus blood load was observed at the time of FeLV reoccurrence.
  
  
  CONCLUSIONS
  Our results demonstrate that ostensibly recovered FeLV provirus-positive cats may act as a source of infection following FeLV reactivation. The virus variants that had largely replaced the inoculation strain had unusually heavily mutated envelopes. The mutations may have led to increased viral fitness and/or changed the mutagenic characteristics of the virus.
authors.affiliation: Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. khungerbuehler@vetclinics.uzh.ch
authors.forename: A Katrin
authors.initials: AK
authors.lastname: Helfer-Hungerbuehler
authors.forename: Valentino
authors.initials: V
authors.lastname: Cattori
authors.forename: Felicitas S
authors.initials: FS
authors.lastname: Boretti
authors.forename: Pete
authors.initials: P
authors.lastname: Ossent
authors.forename: Paula
authors.initials: P
authors.lastname: Grest
authors.forename: Manfred
authors.initials: M
authors.lastname: Reinacher
authors.forename: Manfred
authors.initials: M
authors.lastname: Henrich
authors.forename: Eva
authors.initials: E
authors.lastname: Bauer
authors.forename: Kim
authors.initials: K
authors.lastname: Bauer-Pham
authors.forename: Eva
authors.initials: E
authors.lastname: Niederer
authors.forename: Edgar
authors.initials: E
authors.lastname: Holznagel
authors.forename: Hans
authors.initials: H
authors.lastname: Lutz
authors.forename: Regina
authors.initials: R
authors.lastname: Hofmann-Lehmann
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001769:Blood / Q000821:virology; D018791:CD4 Lymphocyte Count; D002415:Cats; D016000:Cluster Analysis; D005260:Female; D016089:Immunodeficiency Virus, Feline / Q000302:isolation & purification; D005256:Leukemia Virus, Feline / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D016393:Lymphoma, B-Cell / Q000662:veterinary*; D010802:Phylogeny; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D012008:Recurrence; D012463:Saliva / Q000821:virology; D017422:Sequence Analysis, DNA; D014759:Viral Envelope Proteins / Q000235:genetics; D019562:Viral Load; D014766:Viremia / Q000821:virology*; D014775:Virus Activation
chemical_list: D000956:Antigens, Viral; D012367:RNA, Viral; D014759:Viral Envelope Proteins