Retrovirology

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Open Access Research

Dominance of highly divergent feline leukemia virus A progeny variants in a cat with recurrent viremia and fatal lymphoma

A Katrin Helfer-Hungerbuehler1*, Valentino Cattori1, Felicitas S Boretti2, Pete Ossent3, Paula Grest3, Manfred Reinacher4, Manfred Henrich4, Eva Bauer1, Kim Bauer-Pham1, Eva Niederer5, Edgar Holznagel1, Hans Lutz1 and Regina Hofmann-Lehmann1

Author Affiliations

1 Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland

2 Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland

3 Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland

4 Institute of Veterinary Pathology, University of Giessen, Giessen, Germany

5 Institute of Biomedical Engineering, University of Zurich and ETH, Zurich, Switzerland

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Retrovirology 2010, 7:14 doi:10.1186/1742-4690-7-14

Published: 19 February 2010

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.