title: Retroviral DNA--the silent winner: blood transfusion containing latent feline leukemia provirus causes infection and disease in naïve recipient cats.
abstract: BACKGROUND
  The feline leukemia virus (FeLV) is a gamma-retrovirus of domestic cats that was discovered half a century ago. Cats that are infected with FeLV may develop a progressive infection resulting in persistent viremia, immunodeficiency, tumors, anemia and death. A significant number of cats mount a protective immune response that suppresses viremia; these cats develop a regressive infection characterized by the absence of viral replication and the presence of low levels of proviral DNA. The biological importance of these latter provirus carriers is largely unknown.
  
  
  RESULTS
  Here, we demonstrate that ten cats that received a transfusion of blood from aviremic provirus carriers developed active FeLV infections, some with a progressive outcome and the development of fatal FeLV-associated disease. The infection outcome, disease spectrum and evolution into FeLV-C in one cat mirrored those of natural infection. Two cats developed persistent antigenemia; six cats were transiently antigenemic. Reactivation of infection occurred in some cats. One recipient developed non-regenerative anemia associated with FeLV-C, and four others developed a T-cell lymphoma, one with secondary lymphoblastic leukemia. Five of the ten recipient cats received provirus-positive aviremic blood, whereas the other five received provirus- and viral RNA-positive but aviremic blood. Notably, the cats that received blood containing only proviral DNA exhibited a later onset but graver outcome of FeLV infection than the cats that were transfused with blood containing proviral DNA and viral RNA. Leukocyte counts and cytokine analyses indicated that the immune system of the latter cats reacted quicker and more efficiently.
  
  
  CONCLUSIONS
  Our results underline the biological and epidemiological relevance of FeLV provirus carriers and the risk of inadvertent FeLV transmission via blood transfusion and demonstrate the replication capacity of proviral DNA if uncontrolled by the immune system. Our results have implications not only for veterinary medicine, such as the requirement for testing blood donors and blood products for FeLV provirus by sensitive polymerase chain reaction, but are also of general interest by revealing the importance of latent retroviral DNA in infected hosts. When aiming to eliminate a retroviral infection from a population, provirus carriers must be considered.
authors.affiliation: Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. s.nesina@gmx.ch.|Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. s.nesina@gmx.ch.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Nesina
authors.affiliation: Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. khungerbuehler@vetclinics.uzh.ch.|Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. khungerbuehler@vetclinics.uzh.ch.
authors.forename: A
authors.initials: A
authors.lastname: Katrin Helfer-Hungerbuehler
authors.affiliation: Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. briond@vetclinics.uzh.ch.
authors.forename: Barbara
authors.initials: B
authors.lastname: Riond
authors.affiliation: Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. fboretti@vetclinics.uzh.ch.
authors.forename: Felicitas S
authors.initials: FS
authors.lastname: Boretti
authors.affiliation: Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. bwilli@vetclinics.uzh.ch.|Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. bwilli@vetclinics.uzh.ch.
authors.forename: Barbara
authors.initials: B
authors.lastname: Willi
authors.affiliation: Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. mmeli@vetclinics.uzh.ch.|Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. mmeli@vetclinics.uzh.ch.
authors.forename: Marina L
authors.initials: ML
authors.lastname: Meli
authors.affiliation: Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. grest@vetpath.uzh.ch.
authors.forename: Paula
authors.initials: P
authors.lastname: Grest
authors.affiliation: Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. rhofmann@vetclinics.uzh.ch.|Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. rhofmann@vetclinics.uzh.ch.
authors.forename: Regina
authors.initials: R
authors.lastname: Hofmann-Lehmann
mesh_terms: D000740:Anemia / Q000662:veterinary / Q000821:virology; D000818:Animals; D001803:Blood Transfusion / Q000662:veterinary*; D002415:Cats; D004279:DNA, Viral; D005256:Leukemia Virus, Feline / Q000276:immunology / Q000502:physiology; D016582:Leukemia, Feline / Q000276:immunology / Q000401:mortality / Q000635:transmission* / Q000821:virology; D016399:Lymphoma, T-Cell / Q000662:veterinary / Q000821:virology; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000662:veterinary / Q000821:virology; D011533:Proviruses / Q000235:genetics* / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology / Q000635:transmission / Q000662:veterinary* / Q000821:virology; D019562:Viral Load; D017735:Virus Latency / Q000276:immunology; D014779:Virus Replication
chemical_list: D004279:DNA, Viral