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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
. 1987 Jun;84(11):3876–3880. doi: 10.1073/pnas.84.11.3876

Intra-blood-brain barrier synthesis of human immunodeficiency virus antigen and antibody in humans and chimpanzees.

J Goudsmit, L G Epstein, D A Paul, H J van der Helm, G J Dawson, D M Asher, R Yanagihara, A V Wolff, C J Gibbs Jr, D C Gajdusek
PMCID: PMC304979  PMID: 3473487

Abstract

The presence of human immunodeficiency virus (HIV) antigens in cerebrospinal fluid (CSF) was associated with progressive encephalopathy in adult and pediatric patients with acquired immunodeficiency syndrome (AIDS). HIV antigen was detected in CSF from 6 of 7 AIDS patients with progressive encephalopathy. By contrast, HIV antigen, whether free or complexed, was detected in CSF from only 1 of 18 HIV antibody seropositive patients without progressive encephalopathy and from 0 of 8 experimentally infected chimpanzees without clinical signs. Intra-blood-brain barrier synthesis of HIV-specific antibody was demonstrated in the majority of patients with AIDS (9/12) or at risk for AIDS (8/13) as well as in the experimentally infected chimpanzees, indicating HIV-specific B-cell reactivity in the brain without apparent neurological signs. In 6 of 11 patients with HIV infection, antibodies synthesized in the central nervous system were directed against HIV envelope proteins. Active viral expression appears to be necessary for both the immunodeficiency and progressive encephalopathy associated with HIV infection.

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Selected References

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  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. Carne C. A., Tedder R. S., Smith A., Sutherland S., Elkington S. G., Daly H. M., Preston F. E., Craske J. Acute encephalopathy coincident with seroconversion for anti-HTLV-III. Lancet. 1985 Nov 30;2(8466):1206–1208. doi: 10.1016/s0140-6736(85)90740-8. [DOI] [PubMed] [Google Scholar]
  3. Coutinho R. A., Krone W. J., Smit L., Albrecht-van Lent P., van der Noordaa J., Schaesberg W., Goudsmit J. Introduction of lymphadenopathy associated virus or human T lymphotropic virus (LAV/HTLV-III) into the male homosexual community in Amsterdam. Genitourin Med. 1986 Feb;62(1):38–43. doi: 10.1136/sti.62.1.38. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Epstein L. G., Sharer L. R., Oleske J. M., Connor E. M., Goudsmit J., Bagdon L., Robert-Guroff M., Koenigsberger M. R. Neurologic manifestations of human immunodeficiency virus infection in children. Pediatrics. 1986 Oct;78(4):678–687. [PubMed] [Google Scholar]
  5. Gajdusek D. C., Amyx H. L., Gibbs C. J., Jr, Asher D. M., Rodgers-Johnson P., Epstein L. G., Sarin P. S., Gallo R. C., Maluish A., Arthur L. O. Infection of chimpanzees by human T-lymphotropic retroviruses in brain and other tissues from AIDS patients. Lancet. 1985 Jan 5;1(8419):55–56. doi: 10.1016/s0140-6736(85)91011-6. [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. Goudsmit J., Wolters E. C., Bakker M., Smit L., Van der Noordaa J., Hische E. A., Tutuarima J. A., Van der Helm H. J. Intrathecal synthesis of antibodies to HTLV-III in patients without AIDS or AIDS related complex. Br Med J (Clin Res Ed) 1986 May 10;292(6530):1231–1234. doi: 10.1136/bmj.292.6530.1231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goudsmit J., de Wolf F., Paul D. A., Epstein L. G., Lange J. M., Krone W. J., Speelman H., Wolters E. C., Van der Noordaa J., Oleske J. M. Expression of human immunodeficiency virus antigen (HIV-Ag) in serum and cerebrospinal fluid during acute and chronic infection. Lancet. 1986 Jul 26;2(8500):177–180. doi: 10.1016/s0140-6736(86)92485-2. [DOI] [PubMed] [Google Scholar]
  9. Hische E. A., van Meegen M. T., van der Helm H. J. More precise determination of the cerebrospinal fluid IgG index. Clin Chem. 1985 Aug;31(8):1417–1417. [PubMed] [Google Scholar]
  10. Ho D. D., Rota T. R., Schooley R. T., Kaplan J. C., Allan J. D., Groopman J. E., Resnick L., Felsenstein D., Andrews C. A., Hirsch M. S. Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med. 1985 Dec 12;313(24):1493–1497. doi: 10.1056/NEJM198512123132401. [DOI] [PubMed] [Google Scholar]
  11. Klapper P. E., Laing I., Longson M. Rapid non-invasive diagnosis of herpes encephalitis. Lancet. 1981 Sep 19;2(8247):607–609. doi: 10.1016/s0140-6736(81)92744-6. [DOI] [PubMed] [Google Scholar]
  12. Lange J. M., Coutinho R. A., Krone W. J., Verdonck L. F., Danner S. A., van der Noordaa J., Goudsmit J. Distinct IgG recognition patterns during progression of subclinical and clinical infection with lymphadenopathy associated virus/human T lymphotropic virus. Br Med J (Clin Res Ed) 1986 Jan 25;292(6515):228–230. doi: 10.1136/bmj.292.6515.228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lange J. M., Paul D. A., Huisman H. G., de Wolf F., van den Berg H., Coutinho R. A., Danner S. A., van der Noordaa J., Goudsmit J. Persistent HIV antigenaemia and decline of HIV core antibodies associated with transition to AIDS. Br Med J (Clin Res Ed) 1986 Dec 6;293(6560):1459–1462. doi: 10.1136/bmj.293.6560.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lefvert A. K., Link H. IgG production within the central nervous system: a critical review of proposed formulae. Ann Neurol. 1985 Jan;17(1):13–20. doi: 10.1002/ana.410170105. [DOI] [PubMed] [Google Scholar]
  15. Levy J. A., Shimabukuro J., Hollander H., Mills J., Kaminsky L. Isolation of AIDS-associated retroviruses from cerebrospinal fluid and brain of patients with neurological symptoms. Lancet. 1985 Sep 14;2(8455):586–588. [PubMed] [Google Scholar]
  16. Martínez-Martín P., García-Sáiz A., Rapún J. L., Echevarría J. M. Intrathecal synthesis of IgG antibodies to varicella-zoster virus in two cases of acute aseptic meningitis syndrome with no cutaneous lesions. J Med Virol. 1985 Jun;16(2):201–209. doi: 10.1002/jmv.1890160213. [DOI] [PubMed] [Google Scholar]
  17. Neurath A. R., Strick N., Baker L., Krugman S. Radioimmunoassays of hidden viral antigens. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4415–4419. doi: 10.1073/pnas.79.14.4415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Paganelli R., Levinsky R. J., Atherton D. J. Detection of specific antigen within circulating immune complexes: validation of the assay and its application to food antigen-antibody complexes formed in healthy and food-allergic subjects. Clin Exp Immunol. 1981 Oct;46(1):44–53. [PMC free article] [PubMed] [Google Scholar]
  19. Resnick L., diMarzo-Veronese F., Schüpbach J., Tourtellotte W. W., Ho D. D., Müller F., Shapshak P., Vogt M., Groopman J. E., Markham P. D. Intra-blood-brain-barrier synthesis of HTLV-III-specific IgG in patients with neurologic symptoms associated with AIDS or AIDS-related complex. N Engl J Med. 1985 Dec 12;313(24):1498–1504. doi: 10.1056/NEJM198512123132402. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Tibbling G., Link H., Ohman S. Principles of albumin and IgG analyses in neurological disorders. I. Establishment of reference values. Scand J Clin Lab Invest. 1977 Sep;37(5):385–390. doi: 10.1080/00365517709091496. [DOI] [PubMed] [Google Scholar]

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