title: Chromosomal integration of human herpesvirus 6 is the major mode of congenital human herpesvirus 6 infection.
abstract: OBJECTIVE
  We examined the frequency and characteristics of chromosomally integrated human herpesvirus 6 among congenitally infected children.
  
  
  METHODS
  Infants with and without congenital human herpesvirus 6 infection were prospectively monitored. Cord blood mononuclear cell, peripheral blood mononuclear cell, saliva, urine, and hair follicle samples were examined for human herpesvirus 6 DNA. Human herpesvirus 6 RNA, serum antibody, and chromosomally integrated human herpesvirus 6 levels were also assessed.
  
  
  RESULTS
  Among 85 infants, 43 had congenital infections and 42 had postnatal infections. Most congenital infections (86%) resulted from chromosomally integrated human herpesvirus 6; 6 infants (14%) had transplacental infections. Children with chromosomally integrated human herpesvirus 6 had high viral loads in all sites (mean: 5-6 log(10) genomic copies per mug of cellular DNA); among children with transplacental infection or postnatal infection, human herpesvirus 6 DNA was absent in hair samples and inconsistent in other samples, and viral loads were significantly lower. One parent of each child with chromosomally integrated human herpesvirus 6 who had parental hair samples tested had hair containing human herpesvirus 6 DNA. Variant A caused 32% of chromosomally integrated human herpesvirus 6 infections, compared with 2% of postnatal infections. Replicating human herpesvirus 6 was detected only among chromosomally integrated human herpesvirus 6 samples (8% of cord blood mononuclear cells and peripheral blood mononuclear cells). Cord blood human herpesvirus 6 antibody levels were similar among children with chromosomally integrated human herpesvirus 6, transplacental infection, and postnatal infection and between children with maternal and paternal chromosomally integrated human herpesvirus 6 transmission.
  
  
  CONCLUSIONS
  Human herpesvirus 6 congenital infection results primarily from chromosomally integrated virus which is passed through the germ-line. Infants with chromosomally integrated human herpesvirus 6 had high viral loads in all specimens, produced human herpesvirus 6 antibody, and mRNA. The clinical relevance needs study as 1 of 116 newborns may have chromosomally integrated human herpesvirus 6 blood specimens.
authors.affiliation: Department of Pediatrics, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 689, Rochester, NY 14642, USA. caroline_hall@urmc.rochester.edu
authors.forename: Caroline Breese
authors.initials: CB
authors.lastname: Hall
authors.forename: Mary T
authors.initials: MT
authors.lastname: Caserta
authors.forename: Kenneth
authors.initials: K
authors.lastname: Schnabel
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Shelley
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Marino
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Carnahan
authors.forename: Christina
authors.initials: C
authors.lastname: Yoo
authors.forename: Geraldine K
authors.initials: GK
authors.lastname: Lofthus
authors.forename: Michael P
authors.initials: MP
authors.lastname: McDermott