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.ResultsHere, 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-015-0231-z) contains supplementary material, which is available to authorized users.

Diagnosing feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) infection: an update for clinicians

“…14,39 For more detail about other diagnostic methods of FeLV detection, including virus isolation, immunofluorescence for detection of FeLV cell-associated p27 antigen in circulating leukocytes and platelets, and most recently a laboratory-based ELISA to detect p27 antigen (PetChek FeLV 15™), we refer to studies published elsewhere. 49 Although immunofluorescence testing is still recommended as the confirmatory test of choice for FeLV diagnosis in North America, 16 PCR testing is now recommended as the confirmatory test of choice for FeLV diagnosis in Europe 7 and studies evaluating the performance of FeLV PoC test kits using PCR as the confirmatory test are becoming more common. However, one important advantage of PCR testing over all other currently available diagnostic methodologies is its ability to detect regressive FeLV infections.…”

“…47,48 Alarmingly, a recent study demonstrated the ability of regressively infected cats to cause progressive infections in naïve cats following a blood transfusion, highlighting the need to screen potential blood donors for regressive FeLV infection with PCR testing prior to transfusion instead of relying solely performing PoC testing. 49 Although immunofluorescence testing is still recommended as the confirmatory test of choice for FeLV diagnosis in North America, 16 PCR testing is now recommended as the confirmatory test of choice for FeLV diagnosis in Europe 7 and studies evaluating the performance of FeLV PoC test kits using PCR as the confirmatory test are becoming more common. 14,39 We evaluated the performance of three FeLV PoC test kits commercially available in Australia (the same three brands used for FIV testing, i.e.…”

Passive immunization does not provide protection against experimental infection with Mycoplasma haemofelis

“…Fifty days prior to plasma transfusion and experimental infection, the SPF status of all the cats was confirmed by testing for the absence of infection with feline hemoplasmas, feline calicivirus, feline herpesvirus-1, feline coronavirus, feline leukemia and feline immunodeficiency virus, as well as Bartonella henselae and Chlamydia felis , as recently described [ 19 , 30 ]; the absence of Mhf infection was again confirmed by real-time TaqMan ® quantitative (q)PCR [ 12 ] on day 0 prior to plasma transfusion and Mhf inoculation. All donor cats and the cat from the pre-experiment were blood-typed using a commercial immunochromatography technique (Feline Lab Test A + B, Alvedia, France).…”

Aspectos epidemiológicos, clínicos y de diagnóstico del ViLeF y VIF: una revisión actualizada

“…También es posible que sea transmitido a través de mordidas (Krecic et al, 2018 transplacentaria, y de forma iatrogénica por transfusión sanguínea (Aiyaranoi et al, 2018;Krecic et al, 2018;Perharić et al, 2018). Nesina et al (2015) demostraron la transmisión y el desarrollo de la infección por el ViLeF en gatos domésticos que recibieron transfusión sanguínea por parte de donadores seronegativos (sin viremia), ya que el ADN proviral de los leucocitos representa un riesgo de transmisión. Por otro lado, Vobis et al (2003) han documentado la presencia de ARN del ViLeF, hasta 24 horas postalimentación, en la pulga Ctenocephalides felis y también en sus heces.…”