Plaque-associated expression of human herpesvirus 6 in multiple sclerosis.
Journal: 1995/September - Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
PUBMED: 7638210
Abstract:
Representational difference analysis was used to search for pathogens in multiple sclerosis brains. We detected a 341-nucleotide fragment that was 99.4% identical to the major DNA binding protein gene of human herpesvirus 6 (HHV-6). Examination of 86 brain specimens by PCR demonstrated that HHV-6 was present in>> 70% of MS cases and controls and is thus a commensal virus of the human brain. By DNA sequencing, 36/37 viruses from MS cases and controls were typed as HHV-6 variant B group 2. Other herpesviruses, retroviruses, and measles virus were detected infrequently or not at all. HHV-6 expression was examined by immunocytochemistry with monoclonal antibodies against HHV-6 virion protein 101K and DNA binding protein p41. Nuclear staining of oligodendrocytes was observed in MS cases but not in controls, and in MS cases it was observed around plaques more frequently than in uninvolved white matter. MS cases showed prominent cytoplasmic staining of neurons in gray matter adjacent to plaques, although neurons expressing HHV-6 were also found in certain controls. Since destruction of oligodendrocytes is a hallmark of MS, these studies suggest an association of HHV-6 with the etiology or pathogenesis of MS.
Relations:
Content
Citations
(118)
References
(36)
Diseases
(2)
Drugs
(1)
Chemicals
(3)
Organisms
(2)
Processes
(1)
Anatomy
(1)
Similar articles
Articles by the same authors
Discussion board
Proc Natl Acad Sci U S A 92(16): 7440-7444

Plaque-associated expression of human herpesvirus 6 in multiple sclerosis.

Abstract

Representational difference analysis was used to search for pathogens in multiple sclerosis brains. We detected a 341-nucleotide fragment that was 99.4% identical to the major DNA binding protein gene of human herpesvirus 6 (HHV-6). Examination of 86 brain specimens by PCR demonstrated that HHV-6 was present in > 70% of MS cases and controls and is thus a commensal virus of the human brain. By DNA sequencing, 36/37 viruses from MS cases and controls were typed as HHV-6 variant B group 2. Other herpesviruses, retroviruses, and measles virus were detected infrequently or not at all. HHV-6 expression was examined by immunocytochemistry with monoclonal antibodies against HHV-6 virion protein 101K and DNA binding protein p41. Nuclear staining of oligodendrocytes was observed in MS cases but not in controls, and in MS cases it was observed around plaques more frequently than in uninvolved white matter. MS cases showed prominent cytoplasmic staining of neurons in gray matter adjacent to plaques, although neurons expressing HHV-6 were also found in certain controls. Since destruction of oligodendrocytes is a hallmark of MS, these studies suggest an association of HHV-6 with the etiology or pathogenesis of MS.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Kurtzke JF. Epidemiologic evidence for multiple sclerosis as an infection. Clin Microbiol Rev. 1993 Oct;6(4):382–427.[PMC free article] [PubMed] [Google Scholar]
  • Allen I, Brankin B. Pathogenesis of multiple sclerosis--the immune diathesis and the role of viruses. J Neuropathol Exp Neurol. 1993 Mar;52(2):95–105. [PubMed] [Google Scholar]
  • Johnson RT. The virology of demyelinating diseases. Ann Neurol. 1994;36 (Suppl):S54–S60. [PubMed] [Google Scholar]
  • Rice GP. Virus-induced demyelination in man: models for multiple sclerosis. Curr Opin Neurol Neurosurg. 1992 Apr;5(2):188–194. [PubMed] [Google Scholar]
  • Lisitsyn N, Lisitsyn N, Wigler M. Cloning the differences between two complex genomes. Science. 1993 Feb 12;259(5097):946–951. [PubMed] [Google Scholar]
  • Salahuddin SZ, Ablashi DV, Markham PD, Josephs SF, Sturzenegger S, Kaplan M, Halligan G, Biberfeld P, Wong-Staal F, Kramarsky B, et al. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science. 1986 Oct 31;234(4776):596–601. [PubMed] [Google Scholar]
  • Josephs SF, Salahuddin SZ, Ablashi DV, Schachter F, Wong-Staal F, Gallo RC. Genomic analysis of the human B-lymphotropic virus (HBLV). Science. 1986 Oct 31;234(4776):601–603. [PubMed] [Google Scholar]
  • Human herpesvirus-6 strain groups: a nomenclature. Arch Virol. 1993;129(1-4):363–366. [PubMed] [Google Scholar]
  • Tourtellotte WW, Rosario IP, Conrad A, Syndulko K. Human neuro-specimen banking 1961-1992. The National Neurological Research Specimen Bank (a donor program of pre- and post-mortem tissues and cerebrospinal fluid/blood; and a collection of cryopreserved human neurological specimens for neuroscientists). J Neural Transm Suppl. 1993;39:5–15. [PubMed] [Google Scholar]
  • Chou S, Marousek GI. Analysis of interstrain variation in a putative immediate-early region of human herpesvirus 6 DNA and definition of variant-specific sequences. Virology. 1994 Jan;198(1):370–376. [PubMed] [Google Scholar]
  • Gompels UA, Carrigan DR, Carss AL, Arno J. Two groups of human herpesvirus 6 identified by sequence analyses of laboratory strains and variants from Hodgkin's lymphoma and bone marrow transplant patients. J Gen Virol. 1993 Apr;74(Pt 4):613–622. [PubMed] [Google Scholar]
  • Shi SR, Key ME, Kalra KL. Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem. 1991 Jun;39(6):741–748. [PubMed] [Google Scholar]
  • Pellett PE, Sánchez-Martínez D, Dominguez G, Black JB, Anton E, Greenamoyer C, Dambaugh TR. A strongly immunoreactive virion protein of human herpesvirus 6 variant B strain Z29: identification and characterization of the gene and mapping of a variant-specific monoclonal antibody reactive epitope. Virology. 1993 Aug;195(2):521–531. [PubMed] [Google Scholar]
  • Agulnick AD, Thompson JR, Iyengar S, Pearson G, Ablashi D, Ricciardi RP. Identification of a DNA-binding protein of human herpesvirus 6, a putative DNA polymerase stimulatory factor. J Gen Virol. 1993 Jun;74(Pt 6):1003–1009. [PubMed] [Google Scholar]
  • Steeper TA, Horwitz CA, Ablashi DV, Salahuddin SZ, Saxinger C, Saltzman R, Schwartz B. The spectrum of clinical and laboratory findings resulting from human herpesvirus-6 (HHV-6) in patients with mononucleosis-like illnesses not resulting from Epstein-Barr virus or cytomegalovirus. Am J Clin Pathol. 1990 Jun;93(6):776–783. [PubMed] [Google Scholar]
  • Yamanishi K, Okuno T, Shiraki K, Takahashi M, Kondo T, Asano Y, Kurata T. Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet. 1988 May 14;1(8594):1065–1067. [PubMed] [Google Scholar]
  • Cone RW, Huang ML, Ashley R, Corey L. Human herpesvirus 6 DNA in peripheral blood cells and saliva from immunocompetent individuals. J Clin Microbiol. 1993 May;31(5):1262–1267.[PMC free article] [PubMed] [Google Scholar]
  • Hall CB, Long CE, Schnabel KC, Caserta MT, McIntyre KM, Costanzo MA, Knott A, Dewhurst S, Insel RA, Epstein LG. Human herpesvirus-6 infection in children. A prospective study of complications and reactivation. N Engl J Med. 1994 Aug 18;331(7):432–438. [PubMed] [Google Scholar]
  • Caserta MT, Hall CB, Schnabel K, McIntyre K, Long C, Costanzo M, Dewhurst S, Insel R, Epstein LG. Neuroinvasion and persistence of human herpesvirus 6 in children. J Infect Dis. 1994 Dec;170(6):1586–1589. [PubMed] [Google Scholar]
  • Suga S, Yoshikawa T, Asano Y, Kozawa T, Nakashima T, Kobayashi I, Yazaki T, Yamamoto H, Kajita Y, Ozaki T, et al. Clinical and virological analyses of 21 infants with exanthem subitum (roseola infantum) and central nervous system complications. Ann Neurol. 1993 Jun;33(6):597–603. [PubMed] [Google Scholar]
  • Luppi M, Barozzi P, Maiorana A, Marasca R, Torelli G. Human herpesvirus 6 infection in normal human brain tissue. J Infect Dis. 1994 Apr;169(4):943–944. [PubMed] [Google Scholar]
  • Knox KK, Carrigan DR. Disseminated active HHV-6 infections in patients with AIDS. Lancet. 1994 Mar 5;343(8897):577–578. [PubMed] [Google Scholar]
  • Drobyski WR, Knox KK, Majewski D, Carrigan DR. Brief report: fatal encephalitis due to variant B human herpesvirus-6 infection in a bone marrow-transplant recipient. N Engl J Med. 1994 May 12;330(19):1356–1360. [PubMed] [Google Scholar]
  • Knox KK, Carrigan DR. Active human herpesvirus (HHV-6) infection of the central nervous system in patients with AIDS. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 May 1;9(1):69–73. [PubMed] [Google Scholar]
  • Rodriguez M. Multiple sclerosis: basic concepts and hypothesis. Mayo Clin Proc. 1989 May;64(5):570–576. [PubMed] [Google Scholar]
  • Cook SD, Dowling PC. Multiple sclerosis and viruses: an overview. Neurology. 1980 Jul;30(7 Pt 2):80–91. [PubMed] [Google Scholar]
  • Yamanishi K, Kondo K, Mukai T, Kondo T, Nagafuji H, Kato T, Okuno T, Kurata T. Human herpesvirus 6 (HHV-6) infection in the central nervous system. Acta Paediatr Jpn. 1992 Jun;34(3):337–343. [PubMed] [Google Scholar]
  • Ishiguro N, Yamada S, Takahashi T, Takahashi Y, Togashi T, Okuno T, Yamanishi K. Meningo-encephalitis associated with HHV-6 related exanthem subitum. Acta Paediatr Scand. 1990 Oct;79(10):987–989. [PubMed] [Google Scholar]
  • Huang LM, Lee CY, Lee PI, Chen JM, Wang PJ. Meningitis caused by human herpesvirus-6. Arch Dis Child. 1991 Dec;66(12):1443–1444.[PMC free article] [PubMed] [Google Scholar]
  • Sola P, Merelli E, Marasca R, Poggi M, Luppi M, Montorsi M, Torelli G. Human herpesvirus 6 and multiple sclerosis: survey of anti-HHV-6 antibodies by immunofluorescence analysis and of viral sequences by polymerase chain reaction. J Neurol Neurosurg Psychiatry. 1993 Aug;56(8):917–919.[PMC free article] [PubMed] [Google Scholar]
  • Wilborn F, Schmidt CA, Brinkmann V, Jendroska K, Oettle H, Siegert W. A potential role for human herpesvirus type 6 in nervous system disease. J Neuroimmunol. 1994 Jan;49(1-2):213–214. [PubMed] [Google Scholar]
  • Fazakerley JK, Pathak S, Scallan M, Amor S, Dyson H. Replication of the A7(74) strain of Semliki Forest virus is restricted in neurons. Virology. 1993 Aug;195(2):627–637. [PubMed] [Google Scholar]
  • Suckling AJ, Pathak S, Jagelman S, Webb HE. Virus-associated demyelination. A model using avirulent Semliki Forest virus infection of mice. J Neurol Sci. 1978 Nov;39(1):147–154. [PubMed] [Google Scholar]
  • Fazakerley JK, Webb HE. Semliki Forest virus-induced, immune-mediated demyelination: adoptive transfer studies and viral persistence in nude mice. J Gen Virol. 1987 Feb;68(Pt 2):377–385. [PubMed] [Google Scholar]
  • Zurbriggen A, Yamawaki M, Vandevelde M. Restricted canine distemper virus infection of oligodendrocytes. Lab Invest. 1993 Mar;68(3):277–284. [PubMed] [Google Scholar]
  • Rodriguez M, Leibowitz JL, Powell HC, Lampert PW. Neonatal infection with the Daniels strain of Theiler's murine encephalomyelitis virus. Lab Invest. 1983 Dec;49(6):672–679. [PubMed] [Google Scholar]
, et al.
PathoGenesis Corporation, Seattle, WA 98119, USA.
PathoGenesis Corporation, Seattle, WA 98119, USA.
Abstract
Representational difference analysis was used to search for pathogens in multiple sclerosis brains. We detected a 341-nucleotide fragment that was 99.4% identical to the major DNA binding protein gene of human herpesvirus 6 (HHV-6). Examination of 86 brain specimens by PCR demonstrated that HHV-6 was present in > 70% of MS cases and controls and is thus a commensal virus of the human brain. By DNA sequencing, 36/37 viruses from MS cases and controls were typed as HHV-6 variant B group 2. Other herpesviruses, retroviruses, and measles virus were detected infrequently or not at all. HHV-6 expression was examined by immunocytochemistry with monoclonal antibodies against HHV-6 virion protein 101K and DNA binding protein p41. Nuclear staining of oligodendrocytes was observed in MS cases but not in controls, and in MS cases it was observed around plaques more frequently than in uninvolved white matter. MS cases showed prominent cytoplasmic staining of neurons in gray matter adjacent to plaques, although neurons expressing HHV-6 were also found in certain controls. Since destruction of oligodendrocytes is a hallmark of MS, these studies suggest an association of HHV-6 with the etiology or pathogenesis of MS.
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.