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. 1997 Nov;71(11):8632–8641. doi: 10.1128/jvi.71.11.8632-8641.1997

Immunopathologic changes in the thymus during the acute stage of experimentally induced feline immunodeficiency virus infection in juvenile cats.

J C Woo 1, G A Dean 1, N C Pedersen 1, P F Moore 1
PMCID: PMC192327  PMID: 9343221

Abstract

The feline thymus is a target organ and site of viral replication during the acute stage of feline immunodeficiency virus (FIV) infection. This was demonstrated by histologic, immunohistologic, flow cytometric, and virologic tests. Thymic lesions developed after 28 days postinoculation (p.i.) and included thymitis, premature cortical involution, and medullary B-cell hyperplasia with germinal center formation and epithelial distortion. Alterations in thymocyte subsets also developed. Fewer CD4+ CD8- cells were detected at 28 days p.i., while an increase in CD4- CD8+ cells resulted in an inversion of the thymic CD4/CD8 ratio of single-positive cells, similar to events in peripheral blood. Provirus was present in all thymocyte subpopulations including cortical CD1(hi), CD1(lo), and B cells. The CD1(hi) thymocyte proviral burden increased markedly after 56 days p.i., coincident with the presence of infiltrating inflammatory cells. Increased levels of provirus in the CD1(lo) thymocyte subpopulation were detected prior to 56 days p.i. This was likely due to inclusion of infected infiltrating inflammatory cells which could not be differentiated from mature, medullary thymocytes. Proviral levels in B cells also increased from 70 days p.i. Morphologic alterations, productive viral infection, and altered thymocyte subpopulations suggest that thymic function is compromised, thus contributing to the inability of FIV-infected cats to replenish the peripheral T-cell pool.

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Selected References

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  1. Barlough J. E., Ackley C. D., George J. W., Levy N., Acevedo R., Moore P. F., Rideout B. A., Cooper M. D., Pedersen N. C. Acquired immune dysfunction in cats with experimentally induced feline immunodeficiency virus infection: comparison of short-term and long-term infections. J Acquir Immune Defic Syndr. 1991;4(3):219–227. [PubMed] [Google Scholar]
  2. Beebe A. M., Dua N., Faith T. G., Moore P. F., Pedersen N. C., Dandekar S. Primary stage of feline immunodeficiency virus infection: viral dissemination and cellular targets. J Virol. 1994 May;68(5):3080–3091. doi: 10.1128/jvi.68.5.3080-3091.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burke A. P., Anderson D., Benson W., Turnicky R., Mannan P., Liang Y. H., Smialek J., Virmani R. Localization of human immunodeficiency virus 1 RNA in thymic tissues from asymptomatic drug addicts. Arch Pathol Lab Med. 1995 Jan;119(1):36–41. [PubMed] [Google Scholar]
  4. Calabrò M. L., Zanotto C., Calderazzo F., Crivellaro C., Del Mistro A., De Rossi A., Chieco-Bianchi L. HIV-1 infection of the thymus: evidence for a cytopathic and thymotropic viral variant in vivo. AIDS Res Hum Retroviruses. 1995 Jan;11(1):11–19. doi: 10.1089/aid.1995.11.11. [DOI] [PubMed] [Google Scholar]
  5. Colombi S., Deprez M., De Leval L., Humblet C., Greimers R., Defresne M. P., Boniver J., Moutschen M. Thymus involvement in murine acquired immunodeficiency (MAIDS). Thymus. 1994;23(1):27–37. [PubMed] [Google Scholar]
  6. Courgnaud V., Lauré F., Brossard A., Bignozzi C., Goudeau A., Barin F., Bréchot C. Frequent and early in utero HIV-1 infection. AIDS Res Hum Retroviruses. 1991 Mar;7(3):337–341. doi: 10.1089/aid.1991.7.337. [DOI] [PubMed] [Google Scholar]
  7. Dandekar S., Beebe A. M., Barlough J., Phillips T., Elder J., Torten M., Pedersen N. Detection of feline immunodeficiency virus (FIV) nucleic acids in FIV-seronegative cats. J Virol. 1992 Jul;66(7):4040–4049. doi: 10.1128/jvi.66.7.4040-4049.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. De Rossi A., Calabro M. L., Panozzo M., Bernardi D., Caruso B., Tridente G., Chieco-Bianchi L. In vitro studies of HIV-1 infection in thymic lymphocytes: a putative role of the thymus in AIDS pathogenesis. AIDS Res Hum Retroviruses. 1990 Mar;6(3):287–298. doi: 10.1089/aid.1990.6.287. [DOI] [PubMed] [Google Scholar]
  9. Dean G. A., Reubel G. H., Moore P. F., Pedersen N. C. Proviral burden and infection kinetics of feline immunodeficiency virus in lymphocyte subsets of blood and lymph node. J Virol. 1996 Aug;70(8):5165–5169. doi: 10.1128/jvi.70.8.5165-5169.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dua N., Reubel G., Moore P. F., Higgins J., Pedersen N. C. An experimental study of primary feline immunodeficiency virus infection in cats and a historical comparison to acute simian and human immunodeficiency virus diseases. Vet Immunol Immunopathol. 1994 Nov;43(4):337–355. doi: 10.1016/0165-2427(94)90156-2. [DOI] [PubMed] [Google Scholar]
  11. English R. V., Nelson P., Johnson C. M., Nasisse M., Tompkins W. A., Tompkins M. B. Development of clinical disease in cats experimentally infected with feline immunodeficiency virus. J Infect Dis. 1994 Sep;170(3):543–552. doi: 10.1093/infdis/170.3.543. [DOI] [PubMed] [Google Scholar]
  12. Frederick T., Mascola L., Eller A., O'Neil L., Byers B. Progression of human immunodeficiency virus disease among infants and children infected perinatally with human immunodeficiency virus or through neonatal blood transfusion. Los Angeles County Pediatric AIDS Consortium and the Los Angeles County-University of Southern California Medical Center and the University of Southern California School of Medicine. Pediatr Infect Dis J. 1994 Dec;13(12):1091–1097. doi: 10.1097/00006454-199412000-00004. [DOI] [PubMed] [Google Scholar]
  13. Kneitz C., Kerkau T., Müller J., Coulibaly C., Stahl-Hennig C., Hunsmann G., Hünig T., Schimpl A. Early phenotypic and functional alterations in lymphocytes from simian immunodeficiency virus infected macaques. Vet Immunol Immunopathol. 1993 Apr;36(3):239–255. doi: 10.1016/0165-2427(93)90022-v. [DOI] [PubMed] [Google Scholar]
  14. Lackner A. A., Vogel P., Ramos R. A., Kluge J. D., Marthas M. Early events in tissues during infection with pathogenic (SIVmac239) and nonpathogenic (SIVmac1A11) molecular clones of simian immunodeficiency virus. Am J Pathol. 1994 Aug;145(2):428–439. [PMC free article] [PubMed] [Google Scholar]
  15. Li S. L., Kaaya E. E., Ordónez C., Ekman M., Feichtinger H., Putkonen P., Böttiger D., Biberfeld G., Biberfeld P. Thymic immunopathology and progression of SIVsm infection in cynomolgus monkeys. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 May 1;9(1):1–10. [PubMed] [Google Scholar]
  16. McKinney R. E., Jr, Wilfert C. M. Lymphocyte subsets in children younger than 2 years old: normal values in a population at risk for human immunodeficiency virus infection and diagnostic and prognostic application to infected children. Pediatr Infect Dis J. 1992 Aug;11(8):639–644. [PubMed] [Google Scholar]
  17. Moore P. F., Rossitto P. V., Danilenko D. M., Wielenga J. J., Raff R. F., Severns E. Monoclonal antibodies specific for canine CD4 and CD8 define functional T-lymphocyte subsets and high-density expression of CD4 by canine neutrophils. Tissue Antigens. 1992 Aug;40(2):75–85. doi: 10.1111/j.1399-0039.1992.tb01963.x. [DOI] [PubMed] [Google Scholar]
  18. Müller J. G., Czub S., Marx A., Brinkmann R., Plesker R., Müller-Hermelink H. K. Detection of SIV in rhesus monkey thymus stroma cell cultures. Res Virol. 1994 May-Aug;145(3-4):239–244. doi: 10.1016/s0923-2516(07)80028-8. [DOI] [PubMed] [Google Scholar]
  19. Müller J. G., Krenn V., Czub S., Stahl-Hennig C., Coulibaly C., Hunsmann G., Müller-Hermelink H. K. The thymic epithelial reticulum and interdigitating cells in SIV-induced thymus atrophy and its comparison with other forms of thymus involution. Res Virol. 1993 Jan-Feb;144(1):93–98. doi: 10.1016/s0923-2516(06)80017-8. [DOI] [PubMed] [Google Scholar]
  20. Müller J. G., Krenn V., Schindler C., Czub S., Stahl-Hennig C., Coulibaly C., Hunsmann G., Kneitz C., Kerkau T., Rethwilm A. Alterations of thymus cortical epithelium and interdigitating dendritic cells but no increase of thymocyte cell death in the early course of simian immunodeficiency virus infection. Am J Pathol. 1993 Sep;143(3):699–713. [PMC free article] [PubMed] [Google Scholar]
  21. Palmer L. D., Weng N., Levine B. L., June C. H., Lane H. C., Hodes R. J. Telomere length, telomerase activity, and replicative potential in HIV infection: analysis of CD4+ and CD8+ T cells from HIV-discordant monozygotic twins. J Exp Med. 1997 Apr 7;185(7):1381–1386. doi: 10.1084/jem.185.7.1381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Papiernik M., Brossard Y., Mulliez N., Roume J., Brechot C., Barin F., Goudeau A., Bach J. F., Griscelli C., Henrion R. Thymic abnormalities in fetuses aborted from human immunodeficiency virus type 1 seropositive women. Pediatrics. 1992 Feb;89(2):297–301. [PubMed] [Google Scholar]
  23. Phillips T. R., Talbott R. L., Lamont C., Muir S., Lovelace K., Elder J. H. Comparison of two host cell range variants of feline immunodeficiency virus. J Virol. 1990 Oct;64(10):4605–4613. doi: 10.1128/jvi.64.10.4605-4613.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pommier J. P., Gauthier L., Livartowski J., Galanaud P., Boué F., Dulioust A., Marcé D., Ducray C., Sabatier L., Lebeau J. Immunosenescence in HIV pathogenesis. Virology. 1997 Apr 28;231(1):148–154. doi: 10.1006/viro.1997.8512. [DOI] [PubMed] [Google Scholar]
  25. Reubel G. H., George J. W., Higgins J., Pedersen N. C. Effect of chronic feline immunodeficiency virus infection on experimental feline calicivirus-induced disease. Vet Microbiol. 1994 Apr;39(3-4):335–351. doi: 10.1016/0378-1135(94)90169-4. [DOI] [PubMed] [Google Scholar]
  26. Rosenzweig M., Clark D. P., Gaulton G. N. Selective thymocyte depletion in neonatal HIV-1 thymic infection. AIDS. 1993 Dec;7(12):1601–1605. doi: 10.1097/00002030-199312000-00009. [DOI] [PubMed] [Google Scholar]
  27. Schnittman S. M., Denning S. M., Greenhouse J. J., Justement J. S., Baseler M., Kurtzberg J., Haynes B. F., Fauci A. S. Evidence for susceptibility of intrathymic T-cell precursors and their progeny carrying T-cell antigen receptor phenotypes TCR alpha beta + and TCR gamma delta + to human immunodeficiency virus infection: a mechanism for CD4+ (T4) lymphocyte depletion. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7727–7731. doi: 10.1073/pnas.87.19.7727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Valentin H., Nugeyre M. T., Vuillier F., Boumsell L., Schmid M., Barré-Sinoussi F., Pereira R. A. Two subpopulations of human triple-negative thymic cells are susceptible to infection by human immunodeficiency virus type 1 in vitro. J Virol. 1994 May;68(5):3041–3050. doi: 10.1128/jvi.68.5.3041-3050.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wolthers K. C., Bea G., Wisman A., Otto S. A., de Roda Husman A. M., Schaft N., de Wolf F., Goudsmit J., Coutinho R. A., van der Zee A. G. T cell telomere length in HIV-1 infection: no evidence for increased CD4+ T cell turnover. Science. 1996 Nov 29;274(5292):1543–1547. doi: 10.1126/science.274.5292.1543. [DOI] [PubMed] [Google Scholar]
  30. Woo J. C., Moore P. F. A feline homologue of CD1 is defined using a feline-specific monoclonal antibody. Tissue Antigens. 1997 Mar;49(3 Pt 1):244–251. doi: 10.1111/j.1399-0039.1997.tb02745.x. [DOI] [PubMed] [Google Scholar]
  31. Zachar V., Thomas R. A., Goustin A. S. Absolute quantification of target DNA: a simple competitive PCR for efficient analysis of multiple samples. Nucleic Acids Res. 1993 Apr 25;21(8):2017–2018. doi: 10.1093/nar/21.8.2017. [DOI] [PMC free article] [PubMed] [Google Scholar]

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