FeLV-infection: problems and prospects of vaccine prevention and interferon-therapy of feline leukemia

Cover Page

Cite item


Here, we review an overall effectiveness of interferon-based preparations and interferon biosynthesis inducers for treatment of feline leukemia, as well as development of methodological approaches to improve efficacy of interferon therapy. Feline leukemia is a systemic hematopoietic malignancy caused by a single-stranded RNA retrovirus called Feline Leukemia Virus (FeLV) that leads to lethal outcome within about 3 years after the onset. FelV is widely distributed in population of domestic cats worldwide, being often detected in the blood of wild cats, including those of rare and endangered species. In some regions, FeLV prevalence may be high not only among domestic cats, but among wild as well. Currently, there are several commercially available vaccines to protect cats from FeLV infection (e.g., inactivated whole-virion vaccines such as Nobivac adjuvanted Feline 2-FeLV, two-adjuvant subunit vaccine FeLV-derived protein antigens as well as non-adjuvanted vector DNA vaccine). However, none of such vaccines provides durable protection. In addition, vaccination of cats against FeLV is often associated with development of diverse inflammatory, allergic and shock complications, and highly serious side effects such as developing vaccine-associated sarcoma at the injection site that some researchers connect with use of adjuvants like aluminum salts etc. We briefly describe FeLV virus, pathogenetic parametersassociated with FeLV infection as well as current technologies for preventing and treating feline leukemia. A historic background and current state of interferon therapy for FeLV infection as well as associated neoplastic processes in domestic cats and some wild species are evaluated. Possible interventions aimed at improving efficiency of interferon therapy of feline leukemia based on using new recombinant interferon preparations of various types and subtypes, as well as interferon inducers are discussed. In conclusion, it is noted that another interesting and potentially highly promising option in defining strategy of biotherapy associated with modulating IFN system in FeLV-infected animals might be to use of synthetic inducers triggering endogenous IFN production.

About the authors

T. V. Moskvina

Far-Eastern Federal University; Federal Scientific Centre of East Asia Terrestrial Biodiversity, Far-Eastern Branch of the Russian Academy of Sciences

Author for correspondence.
Email: rabchan1992@gmail.com

Tatyana V. Moskvina, Junior Researcher, Laboratory of Ecology of Microorganisms; Junior Researcher, Laboratory of Virology

690088, Vladivostok, Sukhanova str., 8

Phone: +7 902 057-29-64 

Russian Federation

M. Yu. Shchelkanov

Far-Eastern Federal University; Federal Scientific Centre of East Asia Terrestrial Biodiversity, Far-Eastern Branch of the Russian Academy of Sciences; Somov Institute of Epidemiology and Microbiology

Email: rabchan1992@gmail.com

PhD, MD (Biology), Professor of Fundamental Medicine Department; Head of the Laboratory of Virology; Director


Russian Federation

A. V. Tsybulski

Far-Eastern Federal University

Email: rabchan1992@gmail.com

PhD (Biology), Associate Professor, Biochemistry and Biotechnology Department 

Russian Federation


  1. Abraham S., Choi J.G., Ortega N.M., Zhang J., Shankar P., Swamy N.M. Gene therapy with plasmids encoding IFN-β or IFN-α14 confers long-term resistance to HIV-1 in humanized mice. Oncotarget., 2016, vol. 7, pp. 78412–78420. doi: 10.18632/oncotarget.12512
  2. Baird J.R., Feng Z., Xiao H.D., Friedman D., Cottam B., Fox B.A., Kramer G., Leidner R.S., Bell R.B., Young K.H., Crittenden M.R., Gough M.J. STING expression and response to treatment with STING ligands in premalignant and malignant disease. PLoS One, 2018, vol. 13, no. 2: e0192988. doi: 10.1371/journal.pone.0187532
  3. Baldwin S.L., Powel T.D., Sellins K.S., Radecki S.V., Cohen J.J., Milhausen M. The biological effects of five feline IFN-α subtypes. Vet. Immunol. Immunopathol., 2004, vol. 99, pp. 153–167. doi: 10.1016/j.vetimm.2004.01.012
  4. Boesch A., Cattori V., Riond B., Willi B., Meli M.L., Rentsch K.R., Hosie M.J., Hofmann-Lehmann R., Lutz H. Evaluation of the effect of short-term treatment with the integrase inhibitor raltegravir (Isentress™) on the course of progressive feline leukemia virus infection. Vet. Microbiol., 2015, vol. 175, pp. 167–178. doi: 10.1016/j.vetmic.2014.10.031
  5. Brosh R., Rotter V. When mutants gain new powers: news from the mutant p53 field. Nat. Rev. Cancer., 2009, vol. 9, pp. 701–713. doi: 10.1038/nrc2693
  6. Cardellino U., Ciribilli Y., Andreotti V., Modesto P., Menichini P., Fronza G., Pellegrino C., Inga A. Transcriptional properties of feline p53 and its tumour-associated mutants: a yeast-based approach. Mutagenesis, 2007, vol. 22, pp. 417–423. doi: 10.1093/mutage/gem038
  7. Cummins J.M., Tompkins M.B., Olsen R., Tompkins W.A., Lewis M.G. Oral use of human alpha interferon in cats. J. Biol. Response Mod., 1988, vol. 7, pp. 513–523.
  8. De Mari K., Maynard L., Sanquer A., Lebreux B., Eun H.M. Therapeutic effects of recombinant feline interferon-omega on feline leukemia virus (FeLV)-infected and FeLV/feline immunodeficiency virus (FIV)-coinfected symptomatic cats. Vet. Intern. Med., 2004, vol. 18, pp. 477–482. doi: 10.1111/j.1939-1676.2004.tb02570.x
  9. De Noronha F., Grant C.K., Lutz H., Keyes A., Rouston W. Circulating levels of feline leukemia and sarcoma viruses and fibrosarcoma regression in persistently viremic cats. Cancer Res., 1983, vol. 43, pp. 1663–1668.
  10. Fiorito F., Cantiello A., Granato G.E., Navas L., Diffidenti C., De Martino L., Maharajan V., Olivieri F., Pagnini U., Iovane G. Clinical improvement in feline herpesvirus 1 infected cats by oral low dose of interleukin-12 plus interferon-gamma. Comp. Immunol. Microbiol. Infect. Dis., 2016, vol. 48, pp. 41–47. doi: 10.1016/j.cimid.2016.07.006
  11. Garcia-Diaz A., Shin D.S., Moreno B.H., Saco J., Escuin-Ordinas H., Rodriguez G.A., Zaretsky J.M., Sun L., Hugo W., Wang X., Parisi G., Saus C.P., Torrejon D.Y., Graeber T.G., Comin-Anduix B., Hu-Lieskovan S., Damoiseaux R., Lo R.S., Ribas A. Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression. J. Proteome Res., 2020, vol. 19, no. 11, pp. 4393–4397. doi: 10.1016/j.celrep.2017.04.031
  12. Gil S., Leal R.O., McGahie D., Sepúlveda N., Duarte A., Niza M.M.R.E., Tavares L. Oral recombinant feline interferon-omega as an alternative immune modulation therapy in FIV positive cats: clinical and laboratory evaluation. Res. Vet. Sci., 2014, vol. 96, pp. 79–85. doi: 10.1016/j.rvsc.2013.11.007
  13. Grant C.K., De Noronha F., Tusch C., Michalek M.T., McLane M.F. Protection of cats against progressive firbrosarcoma and persistent leukemia virus infection by vaccination with feline leukemia cells. J. Natl. Cancer Inst., 1980, vol. 65, pp. 1285–1292. doi: 10.1093/jnci/65.6.1285
  14. Hartmann K. Feline leukemia virus infection. In: Infectious Diseases of the Dog and Cat, 4th ed. St. Louis, MO: Saunders/ Elsevier, 2012, pp. 67–75.
  15. Hartmann K. Efficacy of antiviral chemotherapy for retrovirus-infected cats. What does the current literature tell us? J. Fel. Med. Surg., 2015, vol. 17, pp. 925–939. doi: 10.1177/1098612X15610676
  16. Hardy W.D., McClelland A.J. Feline leukemia virus: its related diseases and control. Vet. Clin. North Am., 1977, vol. 7, pp. 93–103.
  17. Helfer-Hungerbuehlera A.K., Widmera S., Kesslera Y., Rionda B., Borettib F.S., Grestc P., Lutza H., Hofmann-Lehmanna R. Long-term follow up of feline leukemia virus infection and characterization of viral RNA loads using molecular methods in tissues of cats with different infection outcomes. Virus Res., 2015, vol. 197, pp. 137–150. doi: 10.1016/j.virusres.2014.12.025
  18. Ishiguro H., Kimura M., Takahashi H., Tanaka T., Mizoguchi K., Takeyama H. GADD45A expression is correlated with patient prognosis in esophageal cancer. Oncol. Lett., 2016, vol. 11, pp. 277–282. doi: 10.3892/ol.2015.3882
  19. Hoffman B., Liebermann D.A. Gadd45 in modulation of solid tumors and leukemia. Adv. Exp. Med. Biol., 2013, vol. 793, pp. 21– 33. doi: 10.1007/978-1-4614-8289-5_2
  20. Huang W.S., Kuo Y.H., Kuo H.C., Hsieh M.C., Huang C.Y., Lee K.C., Lee K.F., Shen C.H., Tung S.Y., Teng C.C. CIL-102- induced cell cycle arrest and apoptosis in colorectal cancer cells via upregulation of p21 and GADD45. PLoS One, vol. 12, no. 1: e0168989. doi: 10.1371/journal.pone.0168989
  21. Jarrett O. Pathogenicity of feline leukemia virus is commonly associated with variant viruses. Leukemia, 1992, vol. 6, no. 3, pp. 153–154. doi: 10.1056/NEJMoa2001017
  22. Jas D., Soyer C., De Fornel-Thibaud P., Oberli F., Vernes D., Guigal P.M., Poulet H., Devauchelle P. Adjuvant immunotherapy of feline injection-site sarcomas with the recombinant canarypox virus expressing feline interleukine-2 evaluated in a controlled monocentric clinical trial when used in association with surgery and brachytherapy. Trials Vaccinol., 2015, vol. 4, pp. 1–8. doi: 10.1016/j.trivac.2014.11.001
  23. Kaushiki M., Sha X., Bhatia R., Hoffman B., Liebermann D. Loss of stress sensor GADD45a accelerates BCR-ABL-driven leukemogenesis. Blood, 2011, vol. 118, no. 21: 1668. doi: 10.1182/blood.V118.21.1668.1668
  24. Kelm N.E., Zhu Z., Ding V.A., Xiao H., Wakefield M.R., Bai Q., Fang Y. The role of IL-29 in immunity and cancer. Crit. Rev. Oncol. Hematol., 2016, vol. 106, pp. 91–98. doi: 10.1016/j.critrevonc.2016.08.002
  25. Klotz D., Baumgärtner W., Gerhauser I. Type I interferons in the pathogenesis and treatment of canine diseases (Review). Vet. Immunol. Immunopathol., 2017, vol. 191, pp. 80–93. doi: 10.1016/j.vetimm.2017.08.006
  26. Kociba G.J., Garg R.C., Khan K.N.M., Reiter J.A., Chatfield R.C. Effects of orally administered interferon-α on the pathogenesis of feline leukaemia virus-induced erythroid aplasia. Comp. Haematol. Intern., 1995, vol. 5, pp. 79–83. doi: 10.1007/BF00638923
  27. Koníková E., Kusenda J. Altered expression of p53 and MDM2 proteins in hematological malignancies. Neoplasma, 2003, vol. 50, pp. 31–40.
  28. Lasfa A., Zloza A., Cohen-Solal K.A. IFN-lambda therapy: current status and future perspectives. Drug Discov. Today, 2016, vol. 21, pp. 167–171. doi: 10.1016/j.drudis.2015.10.021
  29. Lazear H.M., Nice T.J., Diamond S. Interferon-λ: immune functions at barrier surfaces and beyond. Immun. Rev., 2015, vol. 43, pp. 15–28. doi: 10.1016/j.immuni.2015.07.001
  30. Leal R.O., Gil S., Brito M.T., McGahie D., Niza M.M., Tavares L. The use of oral recombinant feline interferon omega in two cats with type II diabetes mellitus and concurrent feline chronic gingivostomatitis syndrome. Ir. Vet J., 2013, vol. 66, no. 1: 19. doi: 10.1186/2046-0481-66-19
  31. Li S.F., Zhao F.R., Shao J.J., Xie Y.L., Chang H.Y., Zhang Y.G. Interferon-omega: current status in clinical applications (Review). Int. Immunopharmacol., 2017, vol. 52, pp. 253–260. doi: 10.1016/j.intimp.2017.08.028
  32. Li Q., Kawamura K.G., FumiIwata M., Numasaki M., Suzuki N., Shimada H., Tagawa M. Interferon-λ induces G1 phase arrest or apoptosis in oesophageal carcinoma cells and produces anti-tumour effects in combination with anti-cancer agents. Eur. J. Cancer., 2010, vol. 46, pp. 180–190. doi: 10.1016/j.ejca.2009.10.002
  33. Louwerens M., London C.A., Pedersen N.C., Lyons L.A. Feline lymphoma in the post-feline leukemia virus era. J. Vet. Intern. Med., 2005, vol. 19, pp. 329–335. doi: 10.1111/j.1939-1676.2005.tb02703.x
  34. Magimaidas A., Madireddi P., Maifrede S., Mukherjee K., Hoffman B., Liebermann D.A. Gadd45b deficiency promotes premature senescence and skin aging. Oncotarget, 2016, vol. 7, pp. 26935–26948. doi: 10.18632/oncotarget.8854
  35. McCarty J.M., Grant C.K. Feline cytotoxic immune mechanisms against virus-associated leukemia and fibrosarcom. Cel. Immunol., 1983, vol. 81, pp. 157–168. doi: 10.1016/0008-8749(83)90221-6
  36. Mentlik J.A., Cohen A.D., Campbell K.S. Combination immune therapies to enhance anti-tumor responses by NK cells. Front. Immunol., 2013, vol. 4: 481. doi: 10.3389/fimmu.2013.00481
  37. Mocellin S., Lens M.B., Pasquali S., Pilati P., Chiarion S.V. Interferon alpha for the adjuvant treatment of cutaneous melanoma. Cochrane Database Syst. Rev., 2013, vol. 18, no. 6: CD008955. doi: 10.1002/14651858.CD008955.pub2
  38. Moore G.E., DeSantis-Kerr A.C., Guptill L.F., Glickman N.W., Lewis H.B., Glickman L.T. Adverse events after vaccine administration in cats: 2,560 cases (2002–2005). J. Am. Vet. Med. Assoc., 2007, vol. 231, pp. 94–100. doi: 10.2460/javma.231.1.94
  39. Namikawa K., Tsutsumida A., Mizutani T., Tsuchida T., Yamazaki N. Randomized phase III trial of adjuvant therapy with locoregional interferon beta versus surgery alone in stage II/III cutaneous melanoma. Japan Clinical Oncology Group Study (JCOG1309, J-FERON). Jpn. J. Clin. Oncol., 2017, vol. 47, pp. 664–667. doi: 10.1093/jjco/hyx063
  40. Oikawa T., Okuda M., Kaneko N., Watanabe M., Hiraoka H., Itamoto K., Nakaichi M., Mizuno T., Inokuma H. Cloning of the feline GADD45 cDNA and analysis of its mutation in feline lymphoma cell lines. J. Vet. Med. Sci., 2006, vol. 68, pp. 297–301. doi: 10.1292/jvms.68.297
  41. Okuda M., Umeda A., Sakai T., Ohashi T., Momoi Y., Youn H.Y., Watari T., Goitsuka R., Tsujimoto H., Hasegawa A. Cloning of feline p53 tumor-suppressor gene and its aberration in hematopoietic tumors. Int. J. Cancer, 1994, vol. 58, pp. 602–607. doi: 10.1002/ijc.2910580425
  42. Oren M., Rotter V. Mutant p53 gain-of-function in cancer. Cold Spring Harbor Perspect. Biol., 2010, vol. 2, no. 2: a001107 doi: 10.1093/jmcb/mjaa040
  43. Osterhaus A., Weijer K., Uytdehaag F., Knell P., Jarrett O., Akerblom L., Morein B. Serological responses in cats vaccinated with FeLV ISCOM and an inactivated FeLV vaccine. Vaccine, 1989, vol. 7, pp. 137–141. doi: 10.1016/0264-410X(89)90053-4
  44. Patel M., Carritt K., Lane J., Jayappa H., Stahl M., Bourgeoisb M. Comparative Efficacy of feline leukemia virus (FeLV) inactivated whole-virus vaccine and canarypox virus-vectored vaccine during virulent FeLV challenge and immunosuppression. Clin. Vaccine Immunol., 2015, vol. 22, pp. 798–805. doi: 10.1128/CVI.00034-15
  45. Peller S., Rotter V. TP53 in hematological cancer: low incidence of mutations with significant clinical relevance. Human Mutation, 2003, vol. 21, pp. 277–284. doi: 10.1002/humu.10190
  46. Poulet H., Brunet S., Boularand C., Guiot A.L., Leroy V., Tartaglia J., Minke J., Audonnet J.C., Desmettre P. Efficacy of a canarypox virus-vectored vaccine against feline leukaemia. Vet. Rec., 2003, vol. 153, pp. 141–145. doi: 10.1136/vr.153.5.141
  47. Regan D., Dow S. Manipulation of innate immunity for cancer therapy in dogs. Vet. Sci., 2015, vol. 2, pp. 423–439. doi: 10.3390/vetsci2040423
  48. Richards J., Elston T., Ford R., Gaskell R., Hartmann K., Hurley K., Lappin M., Levy J., Rodan I., Scherk M., Schultz R., Sparkes A. The 2006 American Association of Feline Practitioners Feline Vaccine advisory panel report. J. Am. Vet. Med. Assoc., 2006, vol. 229, pp. 1405–1441. doi: 10.2460/javma.229.9.1405
  49. Robert-Tissot C., Rüegger V.L., Cattori V., Meli M.L., Riond B., Gomes-Keller M.A., Vögtlin A., Wittig B., Juhls C, HofmannLehmann R, Lutz H. The innate antiviral immune system of the cat: molecular tools for the measurement of its state of activation. Vet. Immunol. Immunopathol., 2011, vol. 143, pp. 269–281. doi: 10.1016/j.vetimm.2011.06.005
  50. Raymond D.P., Dickensheets H., O'Brien T.R. Interferon-lambda and therapy for chronic hepatitis C virus infection. Trends Immunol., 2011, vol. 32, pp. 443–450. doi: 10.1016/j.it.2011.07.002
  51. Rovnak J., Quackenbush S.L. Walleye dermal sarcoma virus: molecular biology and oncogenesis. Viruses, 2010, vol. 2, pp. 1984– 1999. doi: 10.3390/v2091984
  52. Sellmann L., Carpinteiro A., Nückel H., Scholtysik R., Siemer D., Klein-Hipass L., Kube D., Dürig J., Dührsen U., Stanelle J., Küppers R. p53 protein expression in chronic lymphocytic leukemia. Leuk. Lymphoma, 2012, vol. 53, pp. 1282–1288. doi: 10.3109/10428194.2011.654115
  53. Shin D.L., Hatesuer B., Bergmann S., Nedelko T., Schughart K. Protection from severe influenza virus infections in mice carrying the Mx1 influenza virus resistance gene strongly depends on genetic background. J. Virol., 2015, vol. 89, pp. 9998–10009. doi: 10.1128/JVI.01305-15
  54. Staeheli P., Grob R., Meier E., Sutcliffe J.G., Haller O. Influenza virus-susceptible mice carry Mx genes with a large deletion or a nonsense mutation. Mol. Cell. Biol., 1988, vol. 8, pp. 4518–4523. doi: 10.1128/MCB.8.10.4518
  55. Stuetzer B., Brunner K., Lutz H., Hartmann K. A trial with 3′-azido-2′,3′-dideoxythymidine and human interferon-α in cats naturally infected with feline leukaemia virus. J. Feline. Med. Surg., 2013, vol. 15, pp. 667–671. doi: 10.1177/1098612X12473468
  56. Tamura R.E., de Vasconcellos J.F., Sarkar D., Libermann T.A., Fisher P.B., Zerbini L.F. GADD45 proteins: central players in tumorigenesis. Curr. Mol. Med., 2012, vol. 12, pp. 634–651. doi: 10.2174/156652412800619978
  57. Tezuka Y., Endo S., Matsui A., Sato A., Saito K., Semba K., Takahashi M., Murakami T. Potential anti-tumor effect of IFN-λ2 (IL-28A) against human lung cancer cells. Lung Cancer, 2012, vol. 78, pp. 185–192. doi: 10.1016/j.lungcan.2012.09.005
  58. Wardley R.C., Berlinski P.J., Thomsen D.R., Meyer A.L., Post L.E. The use of feline herpesvirus and baculovirus as vaccine vectors for the gag and env genes of feline leukaemia virus. J. Gen. Virol., 1992, vol. 73, pp. 1811–1818. doi: 10.1099/0022-1317-73-7-1811
  59. Zhang L., Yang Z., Ma A., Qu Y., Xia S., Xu D., Ge C., Qiu B., Xia Q., Li J., Liu Y. Growth arrest and DNA damage 45G downregulation contributes to Janus kinase/signal transducer and activator of transcription 3 activation and cellular senescence evasion in hepatocellular carcinoma. Hepatology, 2014, vol. 59, pp. 178–189. doi: 10.1002/hep.26628
  60. Zhao H., Ma J., Wang Y., Liu J., Shao Y., Li J., Jiang G. Molecular cloning and functional characterization of eleven subtypes of interferon-α in Amur tigers (Panthera tigris altaica). Dev. Comp. Immunol. 2017, vol. 77, pp. 46–55. doi: 10.1016/j.dci. 2017.07.017Get rights and content
  61. Zorka M., Bajić V., Živković L., Kasapović J., Andjelković U., Spremo-Potparević B. Identification of p53 and its isoforms in human breast carcinoma cells. Sci. World J., 2014, vol. 2014: 618698. doi: 10.1155/2014/618698

Supplementary files

There are no supplementary files to display.

Copyright (c) 2020 Moskvina T.V., Shchelkanov M.Y., Tsybulski A.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 64788 от 02.02.2016.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies