Skip to main content

Advertisement

SpringerLink
Log in

Human herpesvirus 6 infection of the central nervous system

  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Human herpesvirus (HHV) 6 infects all children, usually during the first year of life. High fever is the hallmark of primary infection, with febrile seizures the most common complication. After primary infection, HHV-6 remains latent or persistent at multiple sites, with intermittent reactivation. Many disorders of the central nervous system (CNS) have been linked to HHV-6 reactivation, including chronic seizure disorders, encephalitis, and demyelinating disorders including multiple sclerosis. Although multiple studies have pieced together an understanding of the molecular organization, viral characteristics, immunology, and epidemiology of HHV-6, the true role of this virus in diseases of the CNS is still unfolding.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Salahuddin SZ, Ablashi DV, Markham PD, et al.: Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 1986, 234:596–601.

    Article  PubMed  CAS  Google Scholar 

  2. Yamanishi K, Okuno T, Shiraki K, et al.: Identification of human herpesvirus-6 as a causal agent for exanthema subitum. Lancet 1988, 1:1065–1067.

    Article  PubMed  CAS  Google Scholar 

  3. Hall CB, Long CE, Schnabel KC, et al.: Human herpesvirus-6 infection in children. A prospective study of complications and reactivation. N Engl J Med 1994, 331:432–438.

    Article  PubMed  CAS  Google Scholar 

  4. Braun DK, Dominguez G, Pellett PE: Human herpesvirus 6. Clin Microbiol Rev 1997, 10:521–567.

    PubMed  CAS  Google Scholar 

  5. Dominguez G, Dambaugh TR, Stamey FR, et al.: Human herpesvirus 6B genome sequence: coding content and comparison with human herpesvirus 6A. J Virol 1999, 73:8040–8052.

    PubMed  CAS  Google Scholar 

  6. Berenberg W, Wright S, Janeway CA: Roseola infantum (exanthem subitum). N Engl J Med 1949, 241:253–259.

    Article  CAS  PubMed  Google Scholar 

  7. Suga S, Suzuki K, Ihira M, et al.: Clinical characteristics of febrile convulsions during primary HHV-6 infection. Arch Dis Child 2000, 82:62–66.

    Article  PubMed  CAS  Google Scholar 

  8. Suga S, Yoshikawa T, Asano Y, et al.: Clinical and virological analyses of 21 infants with exanthema subitum (roseola infantum) and central nervous system complications. Ann Neurol 1993, 33:597–603.

    Article  PubMed  CAS  Google Scholar 

  9. Ahtiluoto S, Mannonen L, Paetau A, et al.: In situ hybridization detection of human herpesvirus 6 in brain tissue from fatal encephalitis. Pediatrics 2000, 105:431–433.

    Article  PubMed  CAS  Google Scholar 

  10. Kamei A, Ichinohe S, Onuma R, et al.: Acute disseminated demyelination due to primary human herpesvirus-6 infection. Eur J Pediatr 1997, 156:709–712.

    Article  PubMed  CAS  Google Scholar 

  11. Lanari M, Papa I, Venturi V, et al.: Congenital infection with human herpesvirus 6 variant B associated with neonatal seizures and poor neurological outcome. J Med Virol 2003, 70:628–632.

    Article  PubMed  Google Scholar 

  12. Kato Z, Kozawa R, Teramoto T, et al.: Acute cerebellitis in primary human herpesvirus-6 infection. Eur J Pediatr 2003, 162:801–803.

    Article  PubMed  Google Scholar 

  13. Santoro F, Kennedy PE, Locatelli G, et al.: CD46 is a cellular receptor for human herpesvirus 6. Cell 1999, 99:817–827.

    Article  PubMed  CAS  Google Scholar 

  14. Albright AV, Lavi E, Black JB, et al.: The effect of human herpesvirus-6 (HHV-6) on cultured human neural cells: oligodendrocytes and microglia. J Neurovirol 1998, 4:486–494.

    PubMed  CAS  Google Scholar 

  15. He J, McCarthy M, Zhou Y, et al.: Infection of primary human fetal astrocytes by human herpesvirus 6. J Virol 1996, 70:1296–1300.

    PubMed  CAS  Google Scholar 

  16. Chan PK, Ng HK, Hui M, Cheng AF: Prevalence and distribution of human herpesvirus 6 variants A and B in adult human brain. J Med Virol 2001, 64:42–46.

    Article  PubMed  CAS  Google Scholar 

  17. Cuomo L, Trivedi P, Cardillo MR, et al.: Human herpesvirus 6 infection in neoplastic and normal brain tissue. J Med Virol 2001, 63:45–51.

    Article  PubMed  CAS  Google Scholar 

  18. Caserta MT, Hall CB, Schnabel K, et al.: Neuroinvasion and persistence of human herpesvirus 6 in children. J Infect Dis 1994, 170:1586–1589.

    PubMed  CAS  Google Scholar 

  19. Hall CB, Caserta MT, Schnabel KC, et al.: Persistence of human herpesvirus 6 according to site and variant: possible greater neurotropism of variant A. Clin Infect Dis 1998, 26:132–137.

    PubMed  CAS  Google Scholar 

  20. Kong H, Baerbig Q, Duncan L, et al.: Human herpesvirus type 6 indirectly enhances oligodendrocyte cell death. J Neurovirol 2003, 9:539–550.

    PubMed  CAS  Google Scholar 

  21. Yoshikawa T, Asano Y, Ihira M, et al.: Human herpesvirus 6 viremia in bone marrow transplant recipients: clinical features and risk factors. J Infect Dis 2002, 185:847–853. This is a carefully performed prospective study using viral culture to examine the frequency of HHV-6 reactivation and associated clinical findings in BMT patients.

    Article  PubMed  Google Scholar 

  22. Caserta MT, McDermott MP, Dewhurst S, et al.: Human herpesvirus 6 (HHV6) DNA persistence and reactivation in normal children. J Pediatr 2004, In press.

  23. Norton RA, Caserta MT, Hall CB, et al.: Detection of human herpesvirus 6 by reverse transcription-PCR. J Clin Microbiol 1999, 37:3672–3675.

    PubMed  CAS  Google Scholar 

  24. Kondo K, Nagafuji H, Hata A, et al.: Association of human herpesvirus 6 infection of the central nervous system with recurrence of febrile convulsions. J Infect Dis 1993, 167:1197–1200.

    PubMed  CAS  Google Scholar 

  25. Jee SH, Long CE, Schnabel KC, et al.: Risk of recurrent seizures after a primary human herpesvirus 6-induced febrile seizure. Pediatr Infect Dis J 1998, 17:43–48.

    Article  PubMed  CAS  Google Scholar 

  26. Uesugi H, Shimizu H, Maehara T, et al.: Presence of human herpesvirus 6 and herpes simplex virus detected by polymerase chain reaction in surgical tissue from temporal lobe epileptic patients. Psychiatry Clin Neurosci 2000, 54:589–593.

    Article  PubMed  CAS  Google Scholar 

  27. Donati D, Akhyani N, Fogdell-Hahn A, et al.: Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections. Neurology 2003, 61:1405–1411. This is a thorough evaluation of HHV-6 in brain specimens from patients with epilepsy with multiple methods of detection of active HHV-6 infection. Only a small number of patients were included.

    PubMed  CAS  Google Scholar 

  28. McCullers JA, Lakeman FD, Whitley RJ: Human herpesvirus 6 is associated with focal encephalitis. Clin Infect Dis 1995, 21:571–576.

    PubMed  CAS  Google Scholar 

  29. Zerr DM, Gupta D, Huang ML, et al.: Effect of antivirals on human herpesvirus 6 replication in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002, 34:309–317.

    Article  PubMed  CAS  Google Scholar 

  30. Zerr DM, Gooley TA, Yeung L, et al.: Human herpesvirus 6 reactivation and encephalitis in allogeneic bone marrow transplant recipients. Clin Infect Dis 2001, 33:763–771.

    Article  PubMed  CAS  Google Scholar 

  31. Wang FZ, Linde A, Hagglund H, et al.: Human herpesvirus 6 DNA in cerebrospinal fluid specimens from allogeneic bone marrow transplant patients: does it have clinical significance? Clin Infect Dis 1999, 28:562–568.

    PubMed  CAS  Google Scholar 

  32. Boutolleau D, Fernandez C, Andre E, et al.: Human herpesvirus (HHV)-6 and HHV-7: two closely related viruses with different infection profiles in stem cell transplantation recipients. J Infect Dis 2003, 187:179–186.

    Article  PubMed  Google Scholar 

  33. Wainwright MS, Martin PL, Morse RP, et al.: Human herpesvirus 6 limbic encephalitis after stem cell transplantation. Ann Neurol 2001, 50:612–619. This is one of the largest case studies of well-described patients with evidence of a unique clinical syndrome and active HHV-6 infection of the CNS.

    Article  PubMed  CAS  Google Scholar 

  34. Novoa LJ, Nagra RM, Nakawatase T, et al.: Fulminant demyelinating encephalomyelitis associated with productive HHV-6 infection in an immunocompetent adult. J Med Virol 1997, 52:301–308.

    Article  PubMed  CAS  Google Scholar 

  35. Mock DJ, Powers JM, Goodman AD, et al.: Association of human herpesvirus 6 with the demyelinative lesions of progressive multifocal leukoencephalopathy. J Neurovirol 1999, 5:363–373.

    PubMed  CAS  Google Scholar 

  36. Daibata M, Hatakeyama N, Kamioka M, et al.: Detection of human herpesvirus 6 and JC virus in progressive multifocal leukoencephalopathy complicating follicular lymphoma. Am J Hematol 2001, 67:200–205.

    Article  PubMed  CAS  Google Scholar 

  37. Challoner PB, Smith KT, Parker JD, et al.: Plaque-associated expression of human herpesvirus 6 in multiple sclerosis. Proc Natl Acad Sci U S A 1995, 92:7440–7444.

    Article  PubMed  CAS  Google Scholar 

  38. Tejada-Simon MV, Zang YC, Hong J, et al.: Detection of viral DNA and immune responses to the human herpesvirus 6 101-kilodalton virion protein in patients with multiple sclerosis and in controls. J Virol 2002, 76:6147–6154.

    Article  PubMed  CAS  Google Scholar 

  39. Berti R, Brennan MD, Soldan SS, et al.: Increased detection of serum HHV-6 DNA sequences during multiple sclerosis (MS) exacerbations and correlation with parameters of MS disease progression. J Neurovirol 2002, 8:250–256.

    Article  PubMed  CAS  Google Scholar 

  40. Alvarez-Lafuente R, Martin-Estefania C, de Las Heras V, et al.: Active human herpesvirus 6 infection in patients with multiple sclerosis. Arch Neurol 2002, 59:929–933.

    Article  PubMed  Google Scholar 

  41. Soldan SS, Berti R, Salem N, et al.: Association of human herpes virus 6 (HHV-6) with multiple sclerosis: increased IgM response to HHV-6 early antigen and detection of serum HHV-6 DNA. Nat Med 1997, 3:1394–1397.

    Article  PubMed  CAS  Google Scholar 

  42. Caselli E, Boni M, Bracci A, et al.: Detection of antibodies directed against human herpesvirus 6 U94/REP in sera of patients affected by multiple sclerosis. J Clin Microbiol 2002, 40:4131–4137.

    Article  PubMed  CAS  Google Scholar 

  43. Chapenko S, Millers A, Nora Z, et al.: Correlation between HHV-6 reactivation and multiple sclerosis disease activity. J Med Virol 2003, 69:111–117.

    Article  PubMed  Google Scholar 

  44. Beck R, Wiendl H, Jahn G, et al.: Human herpesvirus 6 in serum and spinal fluid of patients with multiple sclerosis? Arch Neurol 2003, 60:639; author reply 639–640.

    Article  PubMed  Google Scholar 

  45. Goldberg SH, Albright AV, Lisak RP, Gonzalez-Scarano F: Polymerase chain reaction analysis of human herpesvirus-6 sequences in the sera and cerebrospinal fluid of patients with multiple sclerosis. J Neurovirol 1999, 5:134–139.

    PubMed  CAS  Google Scholar 

  46. Taus C, Pucci E, Cartechini E, et al.: Absence of HHV-6 and HHV-7 in cerebrospinal fluid in relapsing-remitting multiple sclerosis. Acta Neurol Scand 2000, 101:224–228.

    Article  PubMed  CAS  Google Scholar 

  47. Secchiero P, Carrigan DR, Asano Y, et al.: Detection of human herpesvirus 6 in plasma of children with primary infection and immunosuppressed patients by polymerase chain reaction. J Infect Dis 1995, 171:273–280.

    PubMed  CAS  Google Scholar 

  48. Ihira M, Yoshikawa T, Suzuki K, et al.: Monitoring of active HHV-6 infection in bone marrow transplant recipients by real time PCR; comparison to detection of viral DNA in plasma by qualitative PCR. Microbiol Immunol 2002, 46:701–705.

    PubMed  CAS  Google Scholar 

  49. Chiu SS, Cheung CY, Tse CY, Peiris M: Early diagnosis of primary human herpesvirus 6 infection in childhood: serology, polymerase chain reaction, and virus load. J Infect Dis 1998, 178:1250–1256.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, 14642, Rochester, NY, USA

    Mary T. Caserta MD

Authors
  1. Mary T. Caserta MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Caserta, M.T. Human herpesvirus 6 infection of the central nervous system. Curr Infect Dis Rep 6, 316–321 (2004). https://doi.org/10.1007/s11908-004-0054-x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11908-004-0054-x

Keywords

Search

Navigation