Published online September 1, 2008
PEDIATRICS Vol. 122 No. 3 September 2008, pp. 513-520 (doi:10.1542/peds.2007-2838)
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Human Herpesvirus 6 (Including...
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ARTICLE

Chromosomal Integration of Human Herpesvirus 6 Is the Major Mode of Congenital Human Herpesvirus 6 Infection

Caroline Breese Hall, MDa,b, Mary T. Caserta, MDa, Kenneth Schnabel, MBAa, Lynne M. Shelley, BSa, Andrea S. Marino, BSa, Jennifer A. Carnahan, BSa, Christina Yoo, BSa, Geraldine K. Lofthus, PhDb and Michael P. McDermott, PhDc

Departments of a Pediatrics
b Medicine
c Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York

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 log10 genomic copies per µg 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.

Key Words: human herpesvirus 6 • congenital infection • chromosomally integrated infection • transmission

Abbreviations: HHV6—human herpesvirus 6 • CI-HHV6—chromosomally integrated human herpesvirus 6 • TPI—transplacental infection • PNI—postnatal infection • PBMC—peripheral blood mononuclear cell • CBMC—cord blood mononuclear cell • RT—reverse transcription • PCR—polymerase chain reaction • FISH—fluorescence in situ hybridization • CMV—cytomegalovirus

Accepted Dec 18, 2007.


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