title: Decreased expression of endogenous feline leukemia virus in cat lymphomas: a case control study.
abstract: BACKGROUND
  Cats infected with exogenous feline leukemia virus (exFeLV) have a higher chance of lymphoma development than uninfected cats. Furthermore, an increased exFeLV transcription has been detected in lymphomas compared to non-malignant tissues. The possible mechanisms of lymphoma development by exFeLV are insertional mutagenesis or persistent stimulation of host immune cells by viral antigens, bringing them at risk for malignant transformation. Vaccination of cats against exFeLV has in recent years decreased the overall infection rate in most countries. Nevertheless, an increasing number of lymphomas have been diagnosed among exFeLV-negative cats. Endogenous feline leukemia virus (enFeLV) is another retrovirus for which transcription has been observed in cat lymphomas. EnFeLV provirus elements are present in the germline of various cat species and share a high sequence similarity with exFeLV but, due to mutations, are incapable of producing infectious viral particles. However, recombination between exFeLV and enFeLV could produce infectious particles.
  
  
  RESULTS
  We examined the FeLV expression in cats that have developed malignant lymphomas and discussed the possible mechanisms that could have induced malignant transformation. For expression analysis we used next-generation RNA-sequencing (RNA-Seq) and for validation reverse transcription quantitative PCR (RT-qPCR). First, we showed that there was no expression of exFeLV in all samples, which eliminates the possibility of recombination between exFeLV and enFeLV. Next, we analyzed the difference in expression of three enFeLV genes between control and lymphoma samples. Our analysis showed an average of 3.40-fold decreased viral expression for the three genes in lymphoma compared to control samples. The results were confirmed by RT-qPCR.
  
  
  CONCLUSIONS
  There is a decreased expression of enFeLV genes in lymphomas versus control samples, which contradicts previous observations for the exFeLV. Our results suggest that a persistent stimulation of host immune cells is not an appropriate mechanism responsible for malignant transformation caused by feline endogenous retroviruses.
authors: Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna, Medical University of Vienna, A-1030, Vienna, Austria. milica.krunic@univie.ac.at.
authors: Milica
authors: M
authors: Krunic
authors: VetCore Facility for Research, University of Veterinary Medicine Vienna, A-1210, Vienna, Austria. reinhard.ertl@vetmeduni.ac.at.
authors: Reinhard
authors: R
authors: Ertl
authors: VetCore Facility for Research, University of Veterinary Medicine Vienna, A-1210, Vienna, Austria. benedikt.hagen@gmx.de.
authors: Benedikt
authors: B
authors: Hagen
authors: Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna, Medical University of Vienna, A-1030, Vienna, Austria. fritz.sedlazeck@univie.ac.at.
authors: Fritz J
authors: FJ
authors: Sedlazeck
authors: Clinical Laboratory, and Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, CH-8057, Zurich, Switzerland. rhofmann@vetclinics.uzh.ch.
authors: Regina
authors: R
authors: Hofmann-Lehmann
authors: Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna, Medical University of Vienna, A-1030, Vienna, Austria. arndt.von.haeseler@univie.ac.at.|Bioinformatics and Computational Biology, Faculty of Computer Science, University of Vienna, A-1090, Vienna, Austria. arndt.von.haeseler@univie.ac.at.
authors: Arndt
authors: A
authors: von Haeseler
authors: VetCore Facility for Research, University of Veterinary Medicine Vienna, A-1210, Vienna, Austria. dieter.klein@vetmeduni.ac.at.
authors: Dieter
authors: D
authors: Klein
mesh_terms: D000818:Animals; D001483:Base Sequence; D016022:Case-Control Studies; D002371:Cat Diseases / Q000473:pathology / Q000821:virology*; D002415:Cats; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D005256:Leukemia Virus, Feline / Q000235:genetics / Q000378:metabolism*; D008223:Lymphoma / Q000662:veterinary* / Q000821:virology; D008297:Male; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012192:Retroviridae Infections / Q000662:veterinary* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014412:Tumor Virus Infections / Q000662:veterinary* / Q000821:virology
chemical_list: D012367:RNA, Viral