Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Mar 1;89(5):1582–1586. doi: 10.1073/pnas.89.5.1582

Primary cultures of endothelial cells from the human liver sinusoid are permissive for human immunodeficiency virus type 1.

A M Steffan 1, M E Lafon 1, J L Gendrault 1, C Schweitzer 1, C Royer 1, D Jaeck 1, J P Arnaud 1, M P Schmitt 1, A M Aubertin 1, A Kirn 1
PMCID: PMC48496  PMID: 1371878

Abstract

Human endothelial cells isolated from hepatic sinusoids were infected in vitro with human immunodeficiency virus type 1 (HIV-1). An early sign of infection occurring in the culture was the formation of multinucleated cells. By double-labeling immunofluorescence, 5-15% of the cells recognized as endothelial cells owing to the presence of von Willebrand factor were found to contain HIV p24 and gp120 antigens after 2 weeks. Reverse transcriptase activity was released into the medium, and different steps in the process of viral budding were observed by electron microscopy. The virus produced by the endothelial cells was found to be infectious for CEM cells, a human T-cell line. CD4 molecules are present at the surface of the endothelial cells, as demonstrated by immunogold-silver staining and backscattered electron imaging. Treatment with an anti-CD4 antibody abolished productive infection of the sinusoidal endothelial cells. The possibility that endothelial cells of the liver sinusoid are infected in vivo with HIV remains to be clearly shown.

Full text

PDF
1582

Images in this article

Selected References

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

  1. Baroni C. D., Pezzella F., Pezzella M., Macchi B., Vitolo D., Uccini S., Ruco L. P. Expression of HIV in lymph node cells of LAS patients. Immunohistology, in situ hybridization, and identification of target cells. Am J Pathol. 1988 Dec;133(3):498–506. [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Beilke M. A. Vascular endothelium in immunology and infectious disease. Rev Infect Dis. 1989 Mar-Apr;11(2):273–283. doi: 10.1093/clinids/11.2.273. [DOI] [PubMed] [Google Scholar]
  4. Benveniste R. E., Morton W. R., Clark E. A., Tsai C. C., Ochs H. D., Ward J. M., Kuller L., Knott W. B., Hill R. W., Gale M. J. Inoculation of baboons and macaques with simian immunodeficiency virus/Mne, a primate lentivirus closely related to human immunodeficiency virus type 2. J Virol. 1988 Jun;62(6):2091–2101. doi: 10.1128/jvi.62.6.2091-2101.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bilello J. A., Pitts O. M., Hoffman P. M. Characterization of a progressive neurodegenerative disease induced by a temperature-sensitive Moloney murine leukemia virus infection. J Virol. 1986 Aug;59(2):234–241. doi: 10.1128/jvi.59.2.234-241.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Budka H., Costanzi G., Cristina S., Lechi A., Parravicini C., Trabattoni R., Vago L. Brain pathology induced by infection with the human immunodeficiency virus (HIV). A histological, immunocytochemical, and electron microscopical study of 100 autopsy cases. Acta Neuropathol. 1987;75(2):185–198. doi: 10.1007/BF00687080. [DOI] [PubMed] [Google Scholar]
  7. Budka H. Human immunodeficiency virus (HIV) envelope and core proteins in CNS tissues of patients with the acquired immune deficiency syndrome (AIDS). Acta Neuropathol. 1990;79(6):611–619. doi: 10.1007/BF00294238. [DOI] [PubMed] [Google Scholar]
  8. Czapar C. A., Weldon-Linne C. M., Moore D. M., Rhone D. P. Peliosis hepatis in the acquired immunodeficiency syndrome. Arch Pathol Lab Med. 1986 Jul;110(7):611–613. [PubMed] [Google Scholar]
  9. Drouet L., Scrobohaci M. L., Janier M., Baudin B. Endothelial cells: target for the HIV1 virus? Nouv Rev Fr Hematol. 1990;32(1):103–106. [PubMed] [Google Scholar]
  10. Epstein L. G., Sharer L. R., Cho E. S., Myenhofer M., Navia B., Price R. W. HTLV-III/LAV-like retrovirus particles in the brains of patients with AIDS encephalopathy. AIDS Res. 1984;1(6):447–454. doi: 10.1089/aid.1.1983.1.447. [DOI] [PubMed] [Google Scholar]
  11. Gabuzda D. H., Ho D. D., de la Monte S. M., Hirsch M. S., Rota T. R., Sobel R. A. Immunohistochemical identification of HTLV-III antigen in brains of patients with AIDS. Ann Neurol. 1986 Sep;20(3):289–295. doi: 10.1002/ana.410200304. [DOI] [PubMed] [Google Scholar]
  12. Gallo R. C., Sarin P. S., Gelmann E. P., Robert-Guroff M., Richardson E., Kalyanaraman V. S., Mann D., Sidhu G. D., Stahl R. E., Zolla-Pazner S. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):865–867. doi: 10.1126/science.6601823. [DOI] [PubMed] [Google Scholar]
  13. Gendelman H. E., Orenstein J. M., Baca L. M., Weiser B., Burger H., Kalter D. C., Meltzer M. S. The macrophage in the persistence and pathogenesis of HIV infection. AIDS. 1989 Aug;3(8):475–495. doi: 10.1097/00002030-198908000-00001. [DOI] [PubMed] [Google Scholar]
  14. Gyorkey F., Melnick J. L., Gyorkey P. Human immunodeficiency virus in brain biopsies of patients with AIDS and progressive encephalopathy. J Infect Dis. 1987 May;155(5):870–876. doi: 10.1093/infdis/155.5.870. [DOI] [PubMed] [Google Scholar]
  15. Harrison R. L., Boudreau R. Human hepatic sinusoidal endothelial cells in culture produce von Willebrand factor and contain Weibel-Palade bodies. Liver. 1989 Aug;9(4):242–249. doi: 10.1111/j.1600-0676.1989.tb00406.x. [DOI] [PubMed] [Google Scholar]
  16. Hellman L., Smedsröd B., Sandberg H., Pettersson U. Secretion of coagulant factor VIII activity and antigen by in vitro cultivated rat liver sinusoidal endothelial cells. Br J Haematol. 1989 Nov;73(3):348–355. doi: 10.1111/j.1365-2141.1989.tb07751.x. [DOI] [PubMed] [Google Scholar]
  17. Ho D. D., Rota T. R., Hirsch M. S. Infection of human endothelial cells by human T-lymphotropic virus type I. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7588–7590. doi: 10.1073/pnas.81.23.7588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Housset C., Boucher O., Girard P. M., Leibowitch J., Saimot A. G., Bréchot C., Marche C. Immunohistochemical evidence for human immunodeficiency virus-1 infection of liver Kupffer cells. Hum Pathol. 1990 Apr;21(4):404–408. doi: 10.1016/0046-8177(90)90202-g. [DOI] [PubMed] [Google Scholar]
  19. Housset C., Lamas E., Bréchot C. Detection of HIV1 RNA and p24 antigen in HIV1-infected human liver. Res Virol. 1990 Mar-Apr;141(2):153–159. doi: 10.1016/0923-2516(90)90017-d. [DOI] [PubMed] [Google Scholar]
  20. Hoxie J. A., Matthews D. M., Cines D. B. Infection of human endothelial cells by human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7591–7595. doi: 10.1073/pnas.81.23.7591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Koenig S., Gendelman H. E., Orenstein J. M., Dal Canto M. C., Pezeshkpour G. H., Yungbluth M., Janotta F., Aksamit A., Martin M. A., Fauci A. S. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science. 1986 Sep 5;233(4768):1089–1093. doi: 10.1126/science.3016903. [DOI] [PubMed] [Google Scholar]
  22. Kure K., Lyman W. D., Weidenheim K. M., Dickson D. W. Cellular localization of an HIV-1 antigen in subacute AIDS encephalitis using an improved double-labeling immunohistochemical method. Am J Pathol. 1990 May;136(5):1085–1092. [PMC free article] [PubMed] [Google Scholar]
  23. Lewis S. H., Reynolds-Kohler C., Fox H. E., Nelson J. A. HIV-1 in trophoblastic and villous Hofbauer cells, and haematological precursors in eight-week fetuses. Lancet. 1990 Mar 10;335(8689):565–568. doi: 10.1016/0140-6736(90)90349-a. [DOI] [PubMed] [Google Scholar]
  24. Meyenhofer M. F., Epstein L. G., Cho E. S., Sharer L. R. Ultrastructural morphology and intracellular production of human immunodeficiency virus (HIV) in brain. J Neuropathol Exp Neurol. 1987 Jul;46(4):474–484. doi: 10.1097/00005072-198707000-00006. [DOI] [PubMed] [Google Scholar]
  25. Mirra S. S., del Rio C. The fine structure of acquired immunodeficiency syndrome encephalopathy. Arch Pathol Lab Med. 1989 Aug;113(8):858–865. [PubMed] [Google Scholar]
  26. Nagura H., Koshikawa T., Fukuda Y., Asai J. Hepatic vascular endothelial cells heterogenously express surface antigens associated with monocytes, macrophages and T lymphocytes. Virchows Arch A Pathol Anat Histopathol. 1986;409(4):407–416. doi: 10.1007/BF00705413. [DOI] [PubMed] [Google Scholar]
  27. Perkocha L. A., Geaghan S. M., Yen T. S., Nishimura S. L., Chan S. P., Garcia-Kennedy R., Honda G., Stoloff A. C., Klein H. Z., Goldman R. L. Clinical and pathological features of bacillary peliosis hepatis in association with human immunodeficiency virus infection. N Engl J Med. 1990 Dec 6;323(23):1581–1586. doi: 10.1056/NEJM199012063232302. [DOI] [PubMed] [Google Scholar]
  28. Pomerantz R. J., de la Monte S. M., Donegan S. P., Rota T. R., Vogt M. W., Craven D. E., Hirsch M. S. Human immunodeficiency virus (HIV) infection of the uterine cervix. Ann Intern Med. 1988 Mar;108(3):321–327. doi: 10.7326/0003-4819-108-3-321. [DOI] [PubMed] [Google Scholar]
  29. Price R. W., Brew B., Sidtis J., Rosenblum M., Scheck A. C., Cleary P. The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science. 1988 Feb 5;239(4840):586–592. doi: 10.1126/science.3277272. [DOI] [PubMed] [Google Scholar]
  30. Pumarola-Sune T., Navia B. A., Cordon-Cardo C., Cho E. S., Price R. W. HIV antigen in the brains of patients with the AIDS dementia complex. Ann Neurol. 1987 May;21(5):490–496. doi: 10.1002/ana.410210513. [DOI] [PubMed] [Google Scholar]
  31. Re M. C., Furlini G., Cenacchi G., Preda P., La Placa M. Human immunodeficiency virus type 1 infection of endothelial cells in vitro. Microbiologica. 1991 Apr;14(2):149–152. [PubMed] [Google Scholar]
  32. Rostad S. W., Sumi S. M., Shaw C. M., Olson K., McDougall J. K. Human immunodeficiency virus (HIV) infection in brains with AIDS-related leukoencephalopathy. AIDS Res Hum Retroviruses. 1987;3(4):363–373. doi: 10.1089/aid.1987.3.363. [DOI] [PubMed] [Google Scholar]
  33. Schmitt M. P., Gendrault J. L., Schweitzer C., Steffan A. M., Beyer C., Royer C., Jaeck D., Pasquali J. L., Kirn A., Aubertin A. M. Permissivity of primary cultures of human Kupffer cells for HIV-1. AIDS Res Hum Retroviruses. 1990 Aug;6(8):987–991. doi: 10.1089/aid.1990.6.987. [DOI] [PubMed] [Google Scholar]
  34. Schuurman H. J., Krone W. J., Broekhuizen R., Goudsmit J. Expression of RNA and antigens of human immunodeficiency virus type-1 (HIV-1) in lymph nodes from HIV-1 infected individuals. Am J Pathol. 1988 Dec;133(3):516–524. [PMC free article] [PubMed] [Google Scholar]
  35. Scoazec J. Y., Feldmann G. Both macrophages and endothelial cells of the human hepatic sinusoid express the CD4 molecule, a receptor for the human immunodeficiency virus. Hepatology. 1990 Sep;12(3 Pt 1):505–510. doi: 10.1002/hep.1840120310. [DOI] [PubMed] [Google Scholar]
  36. Scoazec J. Y., Marche C., Girard P. M., Houtmann J., Durand-Schneider A. M., Saimot A. G., Benhamou J. P., Feldmann G. Peliosis hepatis and sinusoidal dilation during infection by the human immunodeficiency virus (HIV). An ultrastructural study. Am J Pathol. 1988 Apr;131(1):38–47. [PMC free article] [PubMed] [Google Scholar]
  37. Sharer L. R., Epstein L. G., Cho E. S., Joshi V. V., Meyenhofer M. F., Rankin L. F., Petito C. K. Pathologic features of AIDS encephalopathy in children: evidence for LAV/HTLV-III infection of brain. Hum Pathol. 1986 Mar;17(3):271–284. doi: 10.1016/s0046-8177(83)80220-2. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Smith T. W., DeGirolami U., Hénin D., Bolgert F., Hauw J. J. Human immunodeficiency virus (HIV) leukoencephalopathy and the microcirculation. J Neuropathol Exp Neurol. 1990 Jul;49(4):357–370. doi: 10.1097/00005072-199007000-00001. [DOI] [PubMed] [Google Scholar]
  40. Steffan A. M., Gendrault J. L., McCuskey R. S., McCuskey P. A., Kirn A. Phagocytosis, an unrecognized property of murine endothelial liver cells. Hepatology. 1986 Sep-Oct;6(5):830–836. doi: 10.1002/hep.1840060505. [DOI] [PubMed] [Google Scholar]
  41. Stevenson M., Stanwick T. L., Dempsey M. P., Lamonica C. A. HIV-1 replication is controlled at the level of T cell activation and proviral integration. EMBO J. 1990 May;9(5):1551–1560. doi: 10.1002/j.1460-2075.1990.tb08274.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Swarz J. R., Brooks B. R., Johnson R. T. Spongiform polioencephalomyelopathy caused by a murine retrovirus. II. Ultrastructural localization of virus replication and spongiform changes in the central nervous system. Neuropathol Appl Neurobiol. 1981 Sep-Oct;7(5):365–380. doi: 10.1111/j.1365-2990.1981.tb00239.x. [DOI] [PubMed] [Google Scholar]
  43. Vazeux R., Brousse N., Jarry A., Henin D., Marche C., Vedrenne C., Mikol J., Wolff M., Michon C., Rozenbaum W. AIDS subacute encephalitis. Identification of HIV-infected cells. Am J Pathol. 1987 Mar;126(3):403–410. [PMC free article] [PubMed] [Google Scholar]
  44. Wagner D. D., Olmsted J. B., Marder V. J. Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. J Cell Biol. 1982 Oct;95(1):355–360. doi: 10.1083/jcb.95.1.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Ward J. M., O'Leary T. J., Baskin G. B., Benveniste R., Harris C. A., Nara P. L., Rhodes R. H. Immunohistochemical localization of human and simian immunodeficiency viral antigens in fixed tissue sections. Am J Pathol. 1987 May;127(2):199–205. [PMC free article] [PubMed] [Google Scholar]
  46. Weiser B., Peress N., La Neve D., Eilbott D. J., Seidman R., Burger H. Human immunodeficiency virus type 1 expression in the central nervous system correlates directly with extent of disease. Proc Natl Acad Sci U S A. 1990 May;87(10):3997–4001. doi: 10.1073/pnas.87.10.3997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Welch K., Finkbeiner W., Alpers C. E., Blumenfeld W., Davis R. L., Smuckler E. A., Beckstead J. H. Autopsy findings in the acquired immune deficiency syndrome. JAMA. 1984 Sep 7;252(9):1152–1159. [PubMed] [Google Scholar]
  48. Wiley C. A., Nelson J. A. Role of human immunodeficiency virus and cytomegalovirus in AIDS encephalitis. Am J Pathol. 1988 Oct;133(1):73–81. [PMC free article] [PubMed] [Google Scholar]
  49. Wiley C. A., Schrier R. D., Nelson J. A., Lampert P. W., Oldstone M. B. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7089–7093. doi: 10.1073/pnas.83.18.7089. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES