title: Human herpesvirus 6 DNA levels in cerebrospinal fluid due to primary infection differ from those due to chromosomal viral integration and have implications for diagnosis of encephalitis.
abstract: The prevalence and concentration of human herpesvirus 6 (HHV-6) DNA in the cerebrospinal fluid (CSF) of the immunocompetent in primary infection was compared with that in viral chromosomal integration. Samples from 510 individuals with suspected encephalitis, 200 young children and 310 older children and/or adults, and 12 other patients were tested. HHV-6 DNA concentration (log(10) copies/ml) was measured in CSF, serum, and whole blood using PCR. Serum HHV-6 immunoglobulin G antibody was measured by indirect immunofluorescence. Primary infection was defined by antibody seroconversion and/or a low concentration of HHV-6 DNA (<3.0 log(10) copies/ml) in a seronegative serum. Chromosomal integration was defined by a high concentration of viral DNA in serum (>/=3.5 log(10) copies/ml) or whole blood (>/=6.0 log(10) copies/ml). The prevalences of CSF HHV-6 DNA in primary infection and chromosomal integration were 2.5% and 2.0%, respectively, in the young children (<2 years) and 0% and 1.3%, respectively, in the older children and/or adults. The mean concentration of CSF HHV-6 DNA in 9 children with primary infection (2.4 log(10) copies/ml) was significantly lower than that of 21 patients with viral chromosomal integration (4.0 log(10) copies/ml). Only HHV-6B DNA was found in primary infection, whereas in viral integration, 4 patients had HHV-6A and 17 patients HHV-6B. Apart from primary infection, chromosomal integration is the most likely cause of HHV-6 DNA in the CSF of the immunocompetent. Our results show that any diagnosis of HHV-6 encephalitis or other type of active central nervous system infection should not be made without first excluding chromosomal HHV-6 integration by measuring DNA load in CSF, serum, and/or whole blood.
authors.affiliation: Centre for Virology, Division of Infection and Immunity, Royal Free and University College Medical School (UCL campus), Windeyer Institute of Medical Sciences, 46 Cleveland Street, London W1T 4JF, United Kingdom. k.n.ward@ucl.ac.uk
authors.forename: Katherine N
authors.initials: KN
authors.lastname: Ward
authors.forename: Hoe Nam
authors.initials: HN
authors.lastname: Leong
authors.forename: Anton D
authors.initials: AD
authors.lastname: Thiruchelvam
authors.forename: Claire E
authors.initials: CE
authors.lastname: Atkinson
authors.forename: Duncan A
authors.initials: DA
authors.lastname: Clark
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000032:analysis; D001769:Blood / Q000821:virology; D002555:Cerebrospinal Fluid / Q000821:virology; D002675:Child, Preschool; D002875:Chromosomes / Q000821:virology; D004279:DNA, Viral / Q000134:cerebrospinal fluid*; D018792:Encephalitis, Viral / Q000175:diagnosis* / Q000821:virology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015654:Herpesvirus 6, Human / Q000276:immunology / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D015995:Prevalence; D019349:Roseolovirus Infections / Q000175:diagnosis* / Q000821:virology; D044967:Serum / Q000821:virology; D016662:Virus Integration
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D007074:Immunoglobulin G