Skip to main content

Polymerase Chain Reaction Detection of Herpes Simplex Virus in Cerebrospinal Fluid

  • Chapter
Diagnosis of Human Viruses by Polymerase Chain Reaction Technology

Part of the book series: Frontiers of Virology ((FRVIROLOGY,volume 1))

Summary

Herpes simplex encephalitis (HSE) is a serious disease with significant morbidity and mortality if left untreated. It can be treated with acyclovir, but for this to be effective it must be instituted early during the course of disease. Noninvasive, early diagnosis, however, is presumptive at best, and many patients are treated without a definitive diagnosis.

We have developed a polymerase chain reaction (PCR) for the detection of HSV DNA in the cerebrospinal fluid (CSF) of experimentally infected mice. PCR was compared with viral isolation techniques and immunofluorescence on CSF cells during the course of disease of experimentally infected mice. It was found to be more sensitive than these other methods, and HSV DNA could be detected during the earliest stages of central nervous system infection. The assay has also been used for the detection of HSV DNA in CSF samples from patients with HSE. The results are discussed and compared with those published elsewhere.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Anonymous (1991) Acute diagnosis of herpes simplex encephalitis. Lancet 337:205–206

    Article  Google Scholar 

  • Aurelius E, Johansson B, Sköldenberg B, Staland A, Forsgen M (1991) Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid. Lancet 337:189–192

    Article  PubMed  CAS  Google Scholar 

  • Baringer JR (1978) Herpes simplex infections of the nervous system. In: Vinken P, Bruyn GW (eds) Infections of the nervous system. Elsevier, Amsterdam, pp 145–159 (Handbook of clinical neurology, vol 34, part 2)

    Google Scholar 

  • Bergström T, Andersen O, Vahlne A (1989) Isolation of herpes simplex virus type 1 during first attack of multiple sclerosis. Ann Neurol 26:283–285

    Article  PubMed  Google Scholar 

  • Boerman RH (1991) Herpes simplex encephalitis. An experimental and clinical study on early noninvasive diagnosis. Thesis, Leiden University

    Google Scholar 

  • Boerman RH, Raap AK, van der Ploeg, Peters AGB, Rothbart PH (1987) Rapid diagnosis of HSV-1 encephalitis by radioactive genome detection in cerebrospinal fluid. Lancet ii:94

    Article  Google Scholar 

  • Boerman RH, Peters ACB, Verhey M, Raap AK, van Ekdom LTS, van Eer A, van der Ploeg M (1988) Immunofluorescence detection of herpes simplex virus type 1 antigen in cerebrospinal fluid cells of experimentally infected mice. J Neurol Sci 87:245–254

    Article  PubMed  CAS  Google Scholar 

  • Boerman RH, Arnoldus EPJ, Raap AK, Bloem BR, Verhey M, van Gemert G, Peters ACB, van der Ploeg M (1989) Polymerase chain reaction and viral culture techniques to detect HSV in small volumes of cerebrospinal fluid. An experimental mouse encephalitis study. J Virol Methods 25:189–198

    Article  CAS  Google Scholar 

  • Boerman RH, Arnoldus EPJ, Peters ACB, Bloem BR, Raap AK, van der Ploeg M (1991 a) Polymerase chain reaction for early detection of HSV-DNA in cerebrospinal fluid. An experimental mouse encephalitis study. J Med Virol 33:53–55

    Article  Google Scholar 

  • Boerman RH, Bloem BR, Peters ACB, Raap AK, van der Ploeg M (1991 b) Spread of herpes simplex virus to the cerebrospinal fluid and the meninges in experimental mouse encephalitis. Acta Neuropathol (Berl) (accepted for publication)

    Google Scholar 

  • Boerman RH, Mitro A, Bloem BR, Arnoldus EPJ, Raap AK, Peters ACB, van der Ploeg M (1991c) Detection of herpes simplex virus in ependyma of experimentally infected mice. Acta Virol (Praha) (accepted for publication)

    Google Scholar 

  • Booss J, Esiri MM (1986) Sporadic encephalitis I. In: Viral encephalitis: pathology, diagnosis and management. Blackwell Scientific, Oxford, pp 55–94

    Google Scholar 

  • Brihaye J (1970) Etude des encéphalites herpétiques et des encéphalites necrosantes aigues. Acta Neurol Psych Belg 59:1–114

    Google Scholar 

  • Casey HL (1965) Adaptation of the LBCF microtechnique. In: Standardized diagnostic complement fixation and adaptation to microtest. US Public Health Service, Washington (US Public Health Service monograph no. 74), pp 31–34

    Google Scholar 

  • Cook ML, Stevens JG (1973) Pathogenesis of herpetic neuritis and ganglionitis in mice-evidence for intraaxonal transport of infection. Infect Immun 7:272–288

    PubMed  CAS  Google Scholar 

  • Dayan AD, Stokes MI (1973) Rapid diagnosis of encephalitis by immunofluorescent examination of cerebrospinal fluid cells. Lancet i: 177–179

    Article  Google Scholar 

  • Dyson H, Shimeld C, Hill TJ, Blyth WA, Easty DL (1987) Spread of herpes simplex virus within ocular nerves of the mouse: demonstration of viral antigen in whole mounts of eye tissue. J Gen Virol 68:2989–2995

    Article  PubMed  Google Scholar 

  • Fishman RA (1987) No, brain biopsy need not be done in every patient suspected of having herpes simplex encephalitis. Arch Neurol 44:1291–1292

    Article  PubMed  CAS  Google Scholar 

  • Fleming JO, Ting JYP, Stohlman SA, Weiner LP (1983) Improvements in obtaining and characterizing mouse cerebrospinal fluid. J Neuroimmunol 4:129–140

    Article  PubMed  CAS  Google Scholar 

  • Gleaves CA, Wilson DJ, Wold AD, Smith TF (1985) Detection and serotyping of herpes simplex virus in MRC-5 cells by use of centrifugation and monoclonal antibodies 16 h postinoculation. J Clin Microbiol 21:29–32

    PubMed  CAS  Google Scholar 

  • Hanley DF, Johnson RT, Whitley RJ (1987) Yes, brain biopsy should be a prerequisite for herpes simplex encephalitis treatment. Arch Neurol 44:1289–1290

    Article  PubMed  CAS  Google Scholar 

  • Johnson GD, Davidson RS, McNamee KC, Rüssel G, Goodwin D, Holborrow EJ (1982) Fading of immunofluorescence during microscopy: a study of the phenomenon and its remedy. J Immunol Methods 55:231–242

    Article  PubMed  CAS  Google Scholar 

  • Kimura H, Shibata M, Kuzushima K, Nishikawa K, Nishiyama Y, Morishima T (1990) Detection and direct typing of herpes simplex virus by polymerase chain reaction. Med Microbiol Immunol (Berl) 179:177–184

    Article  CAS  Google Scholar 

  • Kit S, Kit M, Qavi H, Trkula D, Otsuka H (1983) Nucleotide sequence of the herpes simplex type 2 (HSV-2) thymidine kinase gene and predicted amino acid sequence of thymidine kinase polypeptide and its comparison with the HSV-1 thymidine kinase gene. Biochim Biophys Acta 741:158–170

    PubMed  CAS  Google Scholar 

  • Klapper PE, Cleator GM, Dennett C, Lewis AG (1990) Diagnosis of herpes encephalitis via Southern blotting of cerebrospinal fluid DNA amplified by polymerase chain reaction. J Med Virol 32:261–264

    Article  PubMed  CAS  Google Scholar 

  • Koskiniemi M, Vaheri A, Taskinen E (1984) Cerebrospinal fluid alterations in herpes simplex virus encephalitis. Rev Infect Dis 6:609–618

    Article  Google Scholar 

  • Kristensson K, Vahlne A, Persson LA, Lycke E (1978) Neural spread of herpes simplex virus types 1 and 2 in mice after corneal or subcutaneous (footpad) inoculation. J Neurol Sci 35:331–340

    Article  PubMed  CAS  Google Scholar 

  • Leestma JE, Borastein MB, Sheppard DR, Feldman LA (1969) Ultrastructural aspects of herpes simplex infection in organized cultures of mammalian nervous tissue. Lab Invest 20:70–78

    PubMed  CAS  Google Scholar 

  • Lopez C, Dudas G (1979) Replication of herpes simplex virus type 1 in macrophages of resistant and susceptible mice. Infect Immun 23:432–437

    PubMed  CAS  Google Scholar 

  • Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor

    Google Scholar 

  • Medawar PB (1948) Immunity to homologous grafted skin, part 3. Fate of skin homographs transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br J Exp Pathol 299:58–69

    Google Scholar 

  • Nahmias AJ, Whitley AN, Visintine AN, Takei Y, Alford CA Jr, Collaborative Antiviral Study Group (1982) Herpes simplex encephalitis: laboratory evaluations and their diagnostic significance. J Infect Dis 145:829–936

    Article  PubMed  CAS  Google Scholar 

  • Nii S, Kamahora J (1963) Location of herpetic viral antigen in interphase cells. Biken J 6:145–154

    PubMed  CAS  Google Scholar 

  • Peden K, Mounts P, Hayward GS (1982) Homology between mammalian cell DNA sequences and human herpesvirus genomes detected by a hybridization procedure with high-complexity probe. Cell 31:71–80

    Article  PubMed  CAS  Google Scholar 

  • Peters ACB, Versteeg J (1980) Immunofluorescence of CSF cells in viral neurological diseases. In: Den Hartog-Jager WA (ed) Color atlas of CSF cytopathology. Elsevier, Amsterdam

    Google Scholar 

  • Porter-Jordan K, Rosenberg El, Keiser JF, Gross JD, Ross AM, Nasim S, Garrett CT (1990) Nested polymerase chain reaction assay for the detection of cytomegalovirus overcomes false positives caused by contamination with fragmented DNA. J Med Virol 30:85–91

    Article  PubMed  CAS  Google Scholar 

  • Puchhammer-Stöckl E, Popow-Kraupp T, Heinz FX, Mandl CW, Kunz C (1990) Establishment of PCR for the early diagnosis of herpes simplex encephalitis. J Med Virol 32:77–82

    Article  PubMed  Google Scholar 

  • Reed LJ, Muench H (1938) A simple method for estimating fifty percent endpoints. Am J Hyg 27:493–497

    Google Scholar 

  • Richman DD, Cleveland PH, Redfield DC, Oxman MN, Wahl GM (1984) Rapid viral diagnosis. J Infect Dis 149:298–310

    Article  PubMed  CAS  Google Scholar 

  • Roizman B (1961) Virus infections of cells in mitosis: I. Observations on the recruitment of cells in karyokinesis into giant cells inducted by herpes simplex virus and bearing on the site of antigen formation. Virology 13:387–401

    CAS  Google Scholar 

  • Rowley AH, Whitley RJ, Lakeman FD, Wolinsky SM (1990) Rapid detection of herpes-simplex-virus DNA in cerebrospinal fluid of patients with herpes simplex virus encephalitis. Lancet 335:440–441

    Article  PubMed  CAS  Google Scholar 

  • Saiki RK, Scharf S, Faloona F, Mullis KB, Korn GT, Erlich HA, Arnheim N (1985) Enzymatic amplification of globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:1350–1354

    Article  PubMed  CAS  Google Scholar 

  • Saiki RK, Gelfland DH, Stoffel S (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491

    Article  PubMed  CAS  Google Scholar 

  • Salmon VC, Turner RB, Speranza MJ, Overall JC Jr (1986) Rapid detection of herpes simplex virus in clinical specimens by centrifugation and immunoperoxidase staining. J Clin Microbiol 23:683–686

    PubMed  CAS  Google Scholar 

  • Schuster V, Matz B, Wiegand H et al. (1986) Detection of herpes simplex virus and adenovirus DNA by dot-blot hybridization using in vitro synthesized RNA transcripts. J Virol Methods 13:291–299

    Article  PubMed  CAS  Google Scholar 

  • Sidman RL, Angevine JB, Pierce ET (1971) Atlas of the mouse brain and spinal cord. Harvard University Press, Cambridge

    Google Scholar 

  • Sköldenberg B, Jansson S, Wolorit S (1975) HSV type 1 and acute … meningitis. Scand J Infect Dis 7:227–232

    PubMed  Google Scholar 

  • Sköldenberg B, Alestig K, Forkman A, Lövgren K, Norrby R, Stiernstedt G, Forsgren M, Bergstrom T, Dahlqvist E, Frydén A, Olding-Stenkvist E, Uhnoo I, De Vahl K (1984) Acyclovir versus vidarabine in herpes simplex encephalitis. Lancet 2:707–711

    Article  PubMed  Google Scholar 

  • Spaar F-W (1976) Die menschliche Herpes-Simplex-Encephalitis und-Meningitis. Eine klinisch-neuropathologische Untersuchung. Fischer, Stuttgart

    Google Scholar 

  • Taber LH, Brasier F, Couch RB, Greenberg SB, Jones D, Knight V (1976) Diagnosis of herpes simplex virus infection by immunofluorescence. J Clin Microbiol 3:309–312

    PubMed  CAS  Google Scholar 

  • Tenser RB (1978) Ultracentrifugal inoculation of herpes simplex virus. Infect Immun 21:281–285

    PubMed  CAS  Google Scholar 

  • Trotter JL, Brooks BR (1980) Pathophysiology of cerebrospinal fluid immunoglobulins. In: Wood JH (ed) Neurobiology of cerebrospinal fluid. Plenum, New York, pp 465–486

    Google Scholar 

  • Ugolini G, Kuypers HGJM, Strick PL (1989) Transneuronal transfer of herpes virus from peripheral nerves to cortex and brainstem. Science 243:89–91

    Article  PubMed  CAS  Google Scholar 

  • van den Berg FM, van Ooyen AJJ, Volkers H, Walboomers JMM (1984) Heterogeneity in subregions of the terminal repeats of herpes simplex virus type 2 DNA. Intervirology 21:96–103

    Google Scholar 

  • van Loon AM, van der Logt JTM, van der Veen J (1981) Diagnosis of herpes encephalitis by ELISA. Lancet 2:1228–1229

    Google Scholar 

  • van Loon AM, van der Logt JTM, Heessen FWA, van der Veen J (1985 a) Quantitation of immunoglobulin E antibody to cytomegalovirus by antibody capture enzyme-linked immunosorbent assay. J Clin Microbiol 21:558–561

    PubMed  Google Scholar 

  • von Loon AM, van der Logt JTM, Heessen FWA, van der Veen J (1985 b) Use of enzyme-labelled antigen for the detection of immunoglobulin M and A antibody to herpes simplex virus in serum and cerebrospinal fluid. J Med Virol 15:183–195

    Article  PubMed  Google Scholar 

  • van Loon AM, van der Logt JTM, Heessen FWA, Postma B, Peeters MF (1989) Diagnosis of herpes simplex virus encephalitis by detection of virus-specific immunoglobulins A and G in serum and cerebrospinal fluid by using an antibody-capture enzyme-linked immunosorbent assay. J Clin Microbiol 27:1983–1987

    PubMed  Google Scholar 

  • Watson DH, Russell WC, Wildy P (1963) Electron microscopic particle count on herpes virus using the phosphotungstate negative staining technique. Virology 19:250–260

    Article  PubMed  CAS  Google Scholar 

  • Whitley RJ (1990) Herpes simplex virus infections. In: Remington JS, Klein JO (eds) Infections diseases of the fetus and newborn infant. Saunders, Philadelphia, pp 282–305

    Google Scholar 

  • Whitley RJ, Soong SJ, Hirsch MS, Karchmer AW, Dolin R (1981) Herpes simplex encephalitis. Vidarabine and diagnostic problems. N Engl J Med 304:313–318

    CAS  Google Scholar 

  • Whitley RJ, Soong SJ, Linneman C Jr, Liu C, Pazin G, Alford CA (1982) Herpes simplex encephalitis. Clinical assessment. JAMA 247:317–320

    CAS  Google Scholar 

  • Whitley RJ, Alford CA, Hirsch MS et al. (1986) Vidarabine vs acyclovir therapy in herpes encephalitis. N Engl J Med 314:144–149

    Article  PubMed  CAS  Google Scholar 

  • Zurukzoglu S (1937) Über das Vorkommen von Herpesvirus in Liquor Cerebrospinalis. Zentralbl Bakteriol [Orig] 139:86–92

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1992 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Boerman, R.H. et al. (1992). Polymerase Chain Reaction Detection of Herpes Simplex Virus in Cerebrospinal Fluid. In: Becker, Y., Darai, G. (eds) Diagnosis of Human Viruses by Polymerase Chain Reaction Technology. Frontiers of Virology, vol 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84766-0_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-84766-0_10

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-84768-4

  • Online ISBN: 978-3-642-84766-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics