Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1986 Dec;125(3):436–442.

HTLV-III expression in infected lymph nodes and relevance to pathogenesis of lymphadenopathy.

P Biberfeld, K J Chayt, L M Marselle, G Biberfeld, R C Gallo, M E Harper
PMCID: PMC1888459  PMID: 3642987

Abstract

In situ hybridization with a 35S-labeled probe of cryosections from 14 lymph nodes of HTLV-III/LAV-seropositive individuals with lymphadenopathy showed the presence of rare cells containing HTLV-III RNA at levels consistent with virus replication. Positive cells were observed at a frequency of only 1-10 per section. In all lymph nodes studied, including those showing follicular hyperplasia or involution, most of the cells expressing viral RNA were present in the follicular areas. Only a minority of such cells were found outside the follicles. The nature of the follicular, virus-replicating cells was not evident from the processed cryosections. After prolonged autoradiography, another pattern of hybridization was observed, suggesting low levels of viral RNA diffusely distributed throughout most, but not all, follicles. This may represent extracellular virus and/or virus-antibody complexes, but was not consistent with intracellular viral RNA or phagocytosed virus particles. Comparison of hybridization levels in relation to histology suggested a decrease in both the number of HTLV-III replicating cells as well as in the diffusely distributed viral RNA with progression of follicular involution. Our observations indicate that in HTLV-III-infected subjects, lymph node follicles are an important site of virus replication and trapping, suggesting a decisive role of the virus in the characteristic reactive and cytopathogenic changes of HTLV-III-associated lymphadenopathy.

Full text

PDF
436

Images in this article

438Figure 2
on p.438
440Figure 3
on p.440

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  2. Benveniste E., Schroff R., Stevens R. H., Gottlieb M. S. Immunoregulatory T cells in men with a new acquired immunodeficiency syndrome. J Clin Immunol. 1983 Oct;3(4):359–367. doi: 10.1007/BF00915797. [DOI] [PubMed] [Google Scholar]
  3. Bowen D. L., Lane H. C., Fauci A. S. Immunopathogenesis of the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Nov;103(5):704–709. doi: 10.7326/0003-4819-103-5-704. [DOI] [PubMed] [Google Scholar]
  4. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  5. Fauci A. S., Macher A. M., Longo D. L., Lane H. C., Rook A. H., Masur H., Gelmann E. P. NIH conference. Acquired immunodeficiency syndrome: epidemiologic, clinical, immunologic, and therapeutic considerations. Ann Intern Med. 1984 Jan;100(1):92–106. doi: 10.7326/0003-4819-100-1-92. [DOI] [PubMed] [Google Scholar]
  6. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  7. Gallo R. C., Wong-Staal F. A human T-lymphotropic retrovirus (HTLV-III) as the cause of the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Nov;103(5):679–689. doi: 10.7326/0003-4819-103-5-679. [DOI] [PubMed] [Google Scholar]
  8. Gartner S., Markovits P., Markovitz D. M., Betts R. F., Popovic M. Virus isolation from and identification of HTLV-III/LAV-producing cells in brain tissue from a patient with AIDS. JAMA. 1986 Nov 7;256(17):2365–2371. [PubMed] [Google Scholar]
  9. Gartner S., Markovits P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. doi: 10.1126/science.3014648. [DOI] [PubMed] [Google Scholar]
  10. Hahn B. H., Shaw G. M., Arya S. K., Popovic M., Gallo R. C., Wong-Staal F. Molecular cloning and characterization of the HTLV-III virus associated with AIDS. Nature. 1984 Nov 8;312(5990):166–169. doi: 10.1038/312166a0. [DOI] [PubMed] [Google Scholar]
  11. Harper M. E., Marselle L. M., Gallo R. C., Wong-Staal F. Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc Natl Acad Sci U S A. 1986 Feb;83(3):772–776. doi: 10.1073/pnas.83.3.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ioachim H. L., Lerner C. W., Tapper M. L. The lymphoid lesions associated with the acquired immunodeficiency syndrome. Am J Surg Pathol. 1983 Sep;7(6):543–553. doi: 10.1097/00000478-198309000-00005. [DOI] [PubMed] [Google Scholar]
  13. Janossy G., Pinching A. J., Bofill M., Weber J., McLaughlin J. E., Ornstein M., Ivory K., Harris J. R., Favrot M., Macdonald-Burns D. C. An immunohistological approach to persistent lymphadenopathy and its relevance to AIDS. Clin Exp Immunol. 1985 Feb;59(2):257–266. [PMC free article] [PubMed] [Google Scholar]
  14. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  15. Matthaei D., Frahm J., Haase A., Schuster R., Bomsdorf H. Chemical-shift-selective magnetic-resonance imaging of avascular necrosis of the femoral head. Lancet. 1985 Feb 16;1(8425):370–371. doi: 10.1016/s0140-6736(85)91388-1. [DOI] [PubMed] [Google Scholar]
  16. McDougal J. S., Mawle A., Cort S. P., Nicholson J. K., Cross G. D., Scheppler-Campbell J. A., Hicks D., Sligh J. Cellular tropism of the human retrovirus HTLV-III/LAV. I. Role of T cell activation and expression of the T4 antigen. J Immunol. 1985 Nov;135(5):3151–3162. [PubMed] [Google Scholar]
  17. Metroka C. E., Cunningham-Rundles S., Pollack M. S., Sonnabend J. A., Davis J. M., Gordon B., Fernandez R. D., Mouradian J. Generalized lymphadenopathy in homosexual men. Ann Intern Med. 1983 Nov;99(5):585–591. doi: 10.7326/0003-4819-99-5-585. [DOI] [PubMed] [Google Scholar]
  18. Meyer P. R., Yanagihara E. T., Parker J. W., Lukes R. J. A distinctive follicular hyperplasia in the acquired immune deficiency syndrome (AIDS) and the AIDS related complex. A pre-lymphomatous state for B cell lymphomas? Hematol Oncol. 1984 Oct-Dec;2(4):319–347. doi: 10.1002/hon.2900020403. [DOI] [PubMed] [Google Scholar]
  19. Modlin R. L., Hofman F. M., Meyer P. R., Vaccaro S. A., Ammann A. J., Conant M. A., Rea T. H., Taylor C. R. Altered distribution of B and T lymphocytes in lymph-nodes from homosexual men with Kaposi's sarcoma. Lancet. 1983 Oct 1;2(8353):768–771. doi: 10.1016/s0140-6736(83)92300-0. [DOI] [PubMed] [Google Scholar]
  20. Pahwa S., Pahwa R., Saxinger C., Gallo R. C., Good R. A. Influence of the human T-lymphotropic virus/lymphadenopathy-associated virus on functions of human lymphocytes: evidence for immunosuppressive effects and polyclonal B-cell activation by banded viral preparations. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8198–8202. doi: 10.1073/pnas.82.23.8198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  22. Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. doi: 10.1038/313277a0. [DOI] [PubMed] [Google Scholar]
  23. Said J. W., Shintaku I. P., Teitelbaum A., Chien K., Sassoon A. F. Distribution of T-cell phenotypic subsets and surface immunoglobulin-bearing lymphocytes in lymph nodes from male homosexuals with persistent generalized adenopathy: an immunohistochemical and ultrastructural study. Hum Pathol. 1984 Aug;15(8):785–790. doi: 10.1016/s0046-8177(84)80171-9. [DOI] [PubMed] [Google Scholar]
  24. Salahuddin S. Z., Rose R. M., Groopman J. E., Markham P. D., Gallo R. C. Human T lymphotropic virus type III infection of human alveolar macrophages. Blood. 1986 Jul;68(1):281–284. [PubMed] [Google Scholar]
  25. Shaw G. M., Harper M. E., Hahn B. H., Epstein L. G., Gajdusek D. C., Price R. W., Navia B. A., Petito C. K., O'Hara C. J., Groopman J. E. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science. 1985 Jan 11;227(4683):177–182. doi: 10.1126/science.2981429. [DOI] [PubMed] [Google Scholar]
  26. Tenner-Racz K., Racz P., Bofill M., Schulz-Meyer A., Dietrich M., Kern P., Weber J., Pinching A. J., Veronese-Dimarzo F., Popovic M. HTLV-III/LAV viral antigens in lymph nodes of homosexual men with persistent generalized lymphadenopathy and AIDS. Am J Pathol. 1986 Apr;123(1):9–15. [PMC free article] [PubMed] [Google Scholar]
  27. Tenner-Rácz K., Rácz P., Dietrich M., Kern P. Altered follicular dendritic cells and virus-like particles in AIDS and AIDS-related lymphadenopathy. Lancet. 1985 Jan 12;1(8420):105–106. doi: 10.1016/s0140-6736(85)91994-4. [DOI] [PubMed] [Google Scholar]
  28. Wong-Staal F., Shaw G. M., Hahn B. H., Salahuddin S. Z., Popovic M., Markham P., Redfield R., Gallo R. C. Genomic diversity of human T-lymphotropic virus type III (HTLV-III). Science. 1985 Aug 23;229(4715):759–762. doi: 10.1126/science.2992084. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES