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Clinical and Diagnostic Laboratory Immunology logoLink to Clinical and Diagnostic Laboratory Immunology
. 1997 Jan;4(1):33–42. doi: 10.1128/cdli.4.1.33-42.1997

Parameters of disease progression in long-term experimental feline retrovirus (feline immunodeficiency virus and feline leukemia virus) infections: hematology, clinical chemistry, and lymphocyte subsets.

R Hofmann-Lehmann 1, E Holznagel 1, P Ossent 1, H Lutz 1
PMCID: PMC170472  PMID: 9008278

Abstract

After several years of latency, feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) cause fatal disease in the cat. The aim of this study was to determine laboratory parameters characteristic of disease progression which would allow a better description of the asymptomatic phase and a better understanding of the pathogenesis of the two infections. Therefore, experimentally infected cats (FIV and/or FeLV positive) and control animals were observed over a period of 6.5 years under identical conditions. Blood samples were analyzed for the following: complete hematology, clinical chemistry, serum protein electrophoresis, and determination of CD4+ and CD8+ lymphocyte subsets. The following hematological and clinical chemistry parameters were markedly changed in the FIV-infected animals from month 9 onwards: glucose, serum protein, gamma globulins, sodium, urea, phosphorus, lipase, cholesterol, and triglyceride. In FeLV infection, the markedly changed parameters were mean corpuscular volume, mean corpuscular hemoglobin, aspartate aminotransferase, and urea. In contrast to reports of field studies, neither FIV-positive nor FeLV-positive animals developed persistent leukopenia, lymphopenia, or neutropenia. A significant decrease was found in the CD4+/CD8+ ratio in FIV-positive and FIV-FeLV-positive animals mainly due to loss of CD4+ lymphocytes. In FeLV-positive cats, both CD4+ and, to a lesser degree, CD8+ lymphocytes were decreased in long-term infection. The changes in FIV infection may reflect subclinical kidney dysfunction, changes in energy and lipid metabolism, and transient activation of the humoral immune response as described for human immunodeficiency virus (HIV) infections. The changes in FeLV infection may also reflect subclinical kidney dysfunction and, in addition, changes in erythrocyte and immune function of the animals. No severe clinical signs were observed in the FIV-positive cats, while FeLV had a severe influence on the life expectancy of persistently positive cats. In conclusion, several parameters of clinical chemistry and hematology were changed in FIV and FeLV infection. Monitoring of these parameters may prove useful for the evaluation of candidate FIV vaccines and antiretroviral drugs in cats. The many parallels between laboratory parameters in FIV and HIV infection further support the importance of FIV as a model for HIV.

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Selected References

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  1. Ackley C. D., Yamamoto J. K., Levy N., Pedersen N. C., Cooper M. D. Immunologic abnormalities in pathogen-free cats experimentally infected with feline immunodeficiency virus. J Virol. 1990 Nov;64(11):5652–5655. doi: 10.1128/jvi.64.11.5652-5655.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alvarez C., Ramos A. Lipids, lipoproteins, and apoproteins in serum during infection. Clin Chem. 1986 Jan;32(1 Pt 1):142–145. [PubMed] [Google Scholar]
  3. Amadori A., Chieco-Bianchi L. B-cell activation and HIV-1 infection: deeds and misdeeds. Immunol Today. 1990 Oct;11(10):374–379. doi: 10.1016/0167-5699(90)90144-x. [DOI] [PubMed] [Google Scholar]
  4. Beisel W. R., Fiser R. H., Jr Lipid metabolism during infectious illness. Am J Clin Nutr. 1970 Aug;23(8):1069–1079. doi: 10.1093/ajcn/23.8.1069. [DOI] [PubMed] [Google Scholar]
  5. Beisel W. R. Impact of infectious disease upon fat metabolism and immune functions. Cancer Res. 1981 Sep;41(9 Pt 2):3797–3798. [PubMed] [Google Scholar]
  6. Bendinelli M., Pistello M., Lombardi S., Poli A., Garzelli C., Matteucci D., Ceccherini-Nelli L., Malvaldi G., Tozzini F. Feline immunodeficiency virus: an interesting model for AIDS studies and an important cat pathogen. Clin Microbiol Rev. 1995 Jan;8(1):87–112. doi: 10.1128/cmr.8.1.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cotter S. M., Hardy W. D., Jr, Essex M. Association of feline leukemia virus with lymphosarcoma and other disorders in the cat. J Am Vet Med Assoc. 1975 Mar 1;166(5):449–454. [PubMed] [Google Scholar]
  8. Day N. K., O'Reilly-Felice C., Hardy W. D., Jr, Good R. A., Witkin S. S. Circulating immune complexes associated with naturally occurring lymphosarcoma in pet cats. J Immunol. 1980 Dec;125(6):2363–2366. [PubMed] [Google Scholar]
  9. Edgington T. S., Curtiss L. K. Plasma lipoproteins with bioregulatory properties including the capacity to regulate lymphocyte function and the immune response. Cancer Res. 1981 Sep;41(9 Pt 2):3786–3788. [PubMed] [Google Scholar]
  10. Gardner M. B. Simian and feline immunodeficiency viruses: animal lentivirus models for evaluation of AIDS vaccines and antiviral agents. Antiviral Res. 1991 May;15(4):267–286. doi: 10.1016/0166-3542(91)90009-g. [DOI] [PubMed] [Google Scholar]
  11. Grinspoon S. K., Donovan D. S., Jr, Bilezikian J. P. Aetiology and pathogenesis of hormonal and metabolic disorders in HIV infection. Baillieres Clin Endocrinol Metab. 1994 Oct;8(4):735–755. doi: 10.1016/s0950-351x(05)80297-6. [DOI] [PubMed] [Google Scholar]
  12. Grunfeld C., Feingold K. R. The metabolic effects of tumor necrosis factor and other cytokines. Biotherapy. 1991;3(2):143–158. doi: 10.1007/BF02172087. [DOI] [PubMed] [Google Scholar]
  13. Grunfeld C., Pang M., Doerrler W., Shigenaga J. K., Jensen P., Feingold K. R. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1992 May;74(5):1045–1052. doi: 10.1210/jcem.74.5.1373735. [DOI] [PubMed] [Google Scholar]
  14. Hellerstein M. K., Grunfeld C., Wu K., Christiansen M., Kaempfer S., Kletke C., Shackleton C. H. Increased de novo hepatic lipogenesis in human immunodeficiency virus infection. J Clin Endocrinol Metab. 1993 Mar;76(3):559–565. doi: 10.1210/jcem.76.3.8445011. [DOI] [PubMed] [Google Scholar]
  15. Hopper C. D., Sparkes A. H., Gruffydd-Jones T. J., Crispin S. M., Muir P., Harbour D. A., Stokes C. R. Clinical and laboratory findings in cats infected with feline immunodeficiency virus. Vet Rec. 1989 Sep 23;125(13):341–346. doi: 10.1136/vr.125.13.341. [DOI] [PubMed] [Google Scholar]
  16. Hosie M. J. The development of a vaccine against feline immunodeficiency virus. Br Vet J. 1994 Jan-Feb;150(1):25–39. doi: 10.1016/S0007-1935(05)80094-6. [DOI] [PubMed] [Google Scholar]
  17. Ishida T., Taniguchi A., Matsumura S., Washizu T., Tomoda I. Long-term clinical observations on feline immunodeficiency virus infected asymptomatic carriers. Vet Immunol Immunopathol. 1992 Dec;35(1-2):15–22. doi: 10.1016/0165-2427(92)90117-9. [DOI] [PubMed] [Google Scholar]
  18. Ishida T., Tomoda I. Clinical staging of feline immunodeficiency virus infection. Nihon Juigaku Zasshi. 1990 Jun;52(3):645–648. doi: 10.1292/jvms1939.52.645. [DOI] [PubMed] [Google Scholar]
  19. JARRETT W. F., CRAWFORD E. M., MARTIN W. B., DAVIE F. A VIRUS-LIKE PARTICLE ASSOCIATED WITH LEUKEMIA (LYMPHOSARCOMA). Nature. 1964 May 9;202:567–569. doi: 10.1038/202567a0. [DOI] [PubMed] [Google Scholar]
  20. Jarrett O., Yamamoto J. K., Neil J. C. Feline immunodeficiency virus as a model for AIDS vaccination. AIDS. 1990;4 (Suppl 1):S163–S165. [PubMed] [Google Scholar]
  21. Klotz F. W., Cooper M. D. A feline thymocyte antigen defined by a monoclonal antibody (FT2) identifies a subpopulation of non-helper cells capable of specific cytotoxicity. J Immunol. 1986 Apr 1;136(7):2510–2514. [PubMed] [Google Scholar]
  22. Lafrado L. J., Lewis M. G., Mathes L. E., Olsen R. G. Suppression of in vitro neutrophil function by feline leukaemia virus (FeLV) and purified FeLV-p15E. J Gen Virol. 1987 Feb;68(Pt 2):507–513. doi: 10.1099/0022-1317-68-2-507. [DOI] [PubMed] [Google Scholar]
  23. Lane H. C., Masur H., Edgar L. C., Whalen G., Rook A. H., Fauci A. S. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983 Aug 25;309(8):453–458. doi: 10.1056/NEJM198308253090803. [DOI] [PubMed] [Google Scholar]
  24. Lees R. S., Fiser R. H., Jr, Beisel W. R., Bartelloni P. J. Effects of an experimental viral infection on plasma lipid and lipoprotein metabolism. Metabolism. 1972 Sep;21(9):825–833. doi: 10.1016/0026-0495(72)90005-4. [DOI] [PubMed] [Google Scholar]
  25. Lehmann R., Franchini M., Aubert A., Wolfensberger C., Cronier J., Lutz H. Vaccination of cats experimentally infected with feline immunodeficiency virus, using a recombinant feline leukemia virus vaccine. J Am Vet Med Assoc. 1991 Nov 15;199(10):1446–1452. [PubMed] [Google Scholar]
  26. Lehmann R., von Beust B., Niederer E., Condrau M. A., Fierz W., Aubert A., Ackley C. D., Cooper M. D., Tompkins M. B., Lutz H. Immunization-induced decrease of the CD4+:CD8+ ratio in cats experimentally infected with feline immunodeficiency virus. Vet Immunol Immunopathol. 1992 Dec;35(1-2):199–214. doi: 10.1016/0165-2427(92)90132-a. [DOI] [PubMed] [Google Scholar]
  27. Levy J. A. Human immunodeficiency viruses and the pathogenesis of AIDS. JAMA. 1989 May 26;261(20):2997–3006. [PubMed] [Google Scholar]
  28. Linenberger M. L., Beebe A. M., Pedersen N. C., Abkowitz J. L., Dandekar S. Marrow accessory cell infection and alterations in hematopoiesis accompany severe neutropenia during experimental acute infection with feline immunodeficiency virus. Blood. 1995 Feb 15;85(4):941–951. [PubMed] [Google Scholar]
  29. Lutz H., Arnold P., Hübscher U., Egberink H., Pedersen N., Horzinek M. C. Specificity assessment of feline T-lymphotropic lentivirus serology. Zentralbl Veterinarmed B. 1988 Dec;35(10):773–778. doi: 10.1111/j.1439-0450.1988.tb00559.x. [DOI] [PubMed] [Google Scholar]
  30. Lutz H. Die Infektion mit felinem Leukämievirus: Immunologie und Serodiagnostik als Grundlage der Infektionsbekämpfung. 1. Teil. Schweiz Arch Tierheilkd. 1984 Jan;126(1):1–22. [PubMed] [Google Scholar]
  31. Lutz H., Hofmann-Lehmann R., Leutenegger C., Allenspach K., Cuisinier A. M., Cronier J., Duquesne V., Aubert A. Vaccination of cats with recombinant envelope glycoprotein of feline immunodeficiency virus: decreased viral load after challenge infection. AIDS Res Hum Retroviruses. 1996 Mar 20;12(5):431–433. doi: 10.1089/aid.1996.12.431. [DOI] [PubMed] [Google Scholar]
  32. Lutz H., Lehmann R., Winkler G., Kottwitz B., Dittmer A., Wolfensberger C., Arnold P. Das Feline Immunschwächevirus in der Schweiz: Klinik und Epidemiologie im Vergleich mit dem leukämie- und dem Coronavirus. Schweiz Arch Tierheilkd. 1990;132(5):217–225. [PubMed] [Google Scholar]
  33. Lutz H., Pedersen N. C., Durbin R., Theilen G. H. Monoclonal antibodies to three epitopic regions of feline leukemia virus p27 and their use in enzyme-linked immunosorbent assay of p27. J Immunol Methods. 1983 Jan 28;56(2):209–220. doi: 10.1016/0022-1759(83)90413-1. [DOI] [PubMed] [Google Scholar]
  34. Madewell B. R., Jarrett O. Recovery of feline leukaemia virus from non-viraemic cats. Vet Rec. 1983 Apr 9;112(15):339–342. doi: 10.1136/vr.112.15.339. [DOI] [PubMed] [Google Scholar]
  35. Marciani D. J., Kensil C. R., Beltz G. A., Hung C. H., Cronier J., Aubert A. Genetically-engineered subunit vaccine against feline leukaemia virus: protective immune response in cats. Vaccine. 1991 Feb;9(2):89–96. doi: 10.1016/0264-410x(91)90262-5. [DOI] [PubMed] [Google Scholar]
  36. Mathes L. E., Olsen R. G., Hebebrand L. C., Hoover E. A., Schaller J. P., Adams P. W., Nichols W. S. Immunosuppressive properties of a virion polypeptide, a 15,000-dalton protein, from feline leukemia virus. Cancer Res. 1979 Mar;39(3):950–955. [PubMed] [Google Scholar]
  37. Meenan J., Mooney E., Mosquita N., Johnson A. H., Collins P., Feely J., Mulcahy F. M. The impact of HIV disease progression on serum lipoproteins. AIDS. 1992 Dec;6(12):1551–1552. doi: 10.1097/00002030-199212000-00026. [DOI] [PubMed] [Google Scholar]
  38. Miller T. L., Winter H. S., Luginbuhl L. M., Orav E. J., McIntosh K. Pancreatitis in pediatric human immunodeficiency virus infection. J Pediatr. 1992 Feb;120(2 Pt 1):223–227. doi: 10.1016/s0022-3476(05)80431-7. [DOI] [PubMed] [Google Scholar]
  39. Mochizuki M., Jarrett O. Haemadsorption and haemagglutination by feline leukaemia viruses. J Gen Virol. 1985 Feb;66(Pt 2):385–389. doi: 10.1099/0022-1317-66-2-385. [DOI] [PubMed] [Google Scholar]
  40. Morikawa S., Lutz H., Aubert A., Bishop D. H. Identification of conserved and variable regions in the envelope glycoprotein sequences of two feline immunodeficiency viruses isolated in Zurich, Switzerland. Virus Res. 1991 Sep;21(1):53–63. doi: 10.1016/0168-1702(91)90071-3. [DOI] [PubMed] [Google Scholar]
  41. Onions D., Jarrett O., Testa N., Frassoni F., Toth S. Selective effect of feline leukaemia virus on early erythroid precursors. Nature. 1982 Mar 11;296(5853):156–158. doi: 10.1038/296156a0. [DOI] [PubMed] [Google Scholar]
  42. Pedersen N. C., Ho E. W., Brown M. L., Yamamoto J. K. Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome. Science. 1987 Feb 13;235(4790):790–793. doi: 10.1126/science.3643650. [DOI] [PubMed] [Google Scholar]
  43. Pedersen N. C., Theilen G., Keane M. A., Fairbanks L., Mason T., Orser B., Che C. H., Allison C. Studies of naturally transmitted feline leukemia virus infection. Am J Vet Res. 1977 Oct;38(10):1523–1531. [PubMed] [Google Scholar]
  44. Pedersen N. C., Torten M., Rideout B., Sparger E., Tonachini T., Luciw P. A., Ackley C., Levy N., Yamamoto J. Feline leukemia virus infection as a potentiating cofactor for the primary and secondary stages of experimentally induced feline immunodeficiency virus infection. J Virol. 1990 Feb;64(2):598–606. doi: 10.1128/jvi.64.2.598-606.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Poli A., Abramo F., Taccini E., Guidi G., Barsotti P., Bendinelli M., Malvaldi G. Renal involvement in feline immunodeficiency virus infection: a clinicopathological study. Nephron. 1993;64(2):282–288. doi: 10.1159/000187327. [DOI] [PubMed] [Google Scholar]
  46. Poli A., Falcone M. L., Bigalli L., Massi C., Hofmann-Lehmann R., Lombardi S., Bendinelli M., Lutz H. Circulating immune complexes and analysis of renal immune deposits in feline immunodeficiency virus-infected cats. Clin Exp Immunol. 1995 Aug;101(2):254–258. doi: 10.1111/j.1365-2249.1995.tb08347.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Quackenbush S. L., Donahue P. R., Dean G. A., Myles M. H., Ackley C. D., Cooper M. D., Mullins J. I., Hoover E. A. Lymphocyte subset alterations and viral determinants of immunodeficiency disease induction by the feline leukemia virus FeLV-FAIDS. J Virol. 1990 Nov;64(11):5465–5474. doi: 10.1128/jvi.64.11.5465-5474.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Reinacher M., Frese K. Untersuchungen zur Glomerulonephritis bei Hund und Katze. Tierarztl Prax. 1991 Apr;19(2):175–180. [PubMed] [Google Scholar]
  49. Sammalkorpi K., Valtonen V., Kerttula Y., Nikkilä E., Taskinen M. R. Changes in serum lipoprotein pattern induced by acute infections. Metabolism. 1988 Sep;37(9):859–865. doi: 10.1016/0026-0495(88)90120-5. [DOI] [PubMed] [Google Scholar]
  50. Schnittman S. M., Lane H. C., Higgins S. E., Folks T., Fauci A. S. Direct polyclonal activation of human B lymphocytes by the acquired immune deficiency syndrome virus. Science. 1986 Sep 5;233(4768):1084–1086. doi: 10.1126/science.3016902. [DOI] [PubMed] [Google Scholar]
  51. Shelton G. H., Abkowitz J. L., Linenberger M. L., Russell R. G., Grant C. K. Chronic leukopenia associated with feline immunodeficiency virus infection in a cat. J Am Vet Med Assoc. 1989 Jan 15;194(2):253–255. [PubMed] [Google Scholar]
  52. Shelton G. H., Linenberger M. L., Abkowitz J. L. Hematologic abnormalities in cats seropositive for feline immunodeficiency virus. J Am Vet Med Assoc. 1991 Nov 15;199(10):1353–1357. [PubMed] [Google Scholar]
  53. Shelton G. H., Linenberger M. L., Persik M. T., Abkowitz J. L. Prospective hematologic and clinicopathologic study of asymptomatic cats with naturally acquired feline immunodeficiency virus infection. J Vet Intern Med. 1995 May-Jun;9(3):133–140. doi: 10.1111/j.1939-1676.1995.tb03286.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Shor-Posner G., Basit A., Lu Y., Cabrejos C., Chang J., Fletcher M., Mantero-Atienza E., Baum M. K. Hypocholesterolemia is associated with immune dysfunction in early human immunodeficiency virus-1 infection. Am J Med. 1993 May;94(5):515–519. doi: 10.1016/0002-9343(93)90087-6. [DOI] [PubMed] [Google Scholar]
  55. Snyder H. W., Jr, Jones F. R., Day N. K., Hardy W. D., Jr Isolation and characterization of circulating feline leukemia virus-immune complexes from plasma of persistently infected pet cats removed by ex vivo immunosorption. J Immunol. 1982 Jun;128(6):2726–2730. [PubMed] [Google Scholar]
  56. Sparkes A. H., Hopper C. D., Millard W. G., Gruffydd-Jones T. J., Harbour D. A. Feline immunodeficiency virus infection. Clinicopathologic findings in 90 naturally occurring cases. J Vet Intern Med. 1993 Mar-Apr;7(2):85–90. doi: 10.1111/j.1939-1676.1993.tb03174.x. [DOI] [PubMed] [Google Scholar]
  57. Testa N. G., Onions D., Jarrett O., Frassoni F., Eliason J. F. Haemopoietic colony formation (BFU-E, GM-CFC) during the development of pure red cell hypoplasia induced in the cat by feline leukaemia virus. Leuk Res. 1983;7(2):103–116. doi: 10.1016/0145-2126(83)90001-2. [DOI] [PubMed] [Google Scholar]
  58. Tompkins M. B., Nelson P. D., English R. V., Novotney C. Early events in the immunopathogenesis of feline retrovirus infections. J Am Vet Med Assoc. 1991 Nov 15;199(10):1311–1315. [PubMed] [Google Scholar]
  59. Trainin Z., Wernicke D., Ungar-Waron H., Essex M. Suppression of the humoral antibody response in natural retrovirus infections. Science. 1983 May 20;220(4599):858–859. doi: 10.1126/science.6302837. [DOI] [PubMed] [Google Scholar]
  60. Walker C., Canfield P. J., Love D. N. Analysis of leucocytes and lymphocyte subsets for different clinical stages of naturally acquired feline immunodeficiency virus infection. Vet Immunol Immunopathol. 1994 Dec;44(1):1–12. doi: 10.1016/0165-2427(94)90165-1. [DOI] [PubMed] [Google Scholar]
  61. Weijer K., Daams J. H. The presence of leukaemia (lymphosarcoma) and feline leukaemia virus (FeLv) in cats in The Netherlands. J Small Anim Pract. 1976 Oct;17(10):649–659. doi: 10.1111/j.1748-5827.1976.tb06925.x. [DOI] [PubMed] [Google Scholar]
  62. Weinroth S. E., Parenti D. M., Simon G. L. Wasting syndrome in AIDS: pathophysiologic mechanisms and therapeutic approaches. Infect Agents Dis. 1995 Jun;4(2):76–94. [PubMed] [Google Scholar]
  63. Wolf P., Reiser J. R., Fellow J. E., Haghighi P. Pancreatitis in patients with AIDS presumptively due to CMV. J Clin Lab Anal. 1989;3(3):152–155. doi: 10.1002/jcla.1860030304. [DOI] [PubMed] [Google Scholar]
  64. Yamamoto J. K., Hansen H., Ho E. W., Morishita T. Y., Okuda T., Sawa T. R., Nakamura R. M., Pedersen N. C. Epidemiologic and clinical aspects of feline immunodeficiency virus infection in cats from the continental United States and Canada and possible mode of transmission. J Am Vet Med Assoc. 1989 Jan 15;194(2):213–220. [PubMed] [Google Scholar]

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