The proposed studies focus on the clinical, epidemiologic, and virologic characterization of primary HHV-6 infection and the possible neurotropism of some HHV-6 strains. Preliminary studies at Rochester suggest that HHV-6 is a major cause of morbidity and healthcare costs for children in the first two years of life, accounting for 11% of Emergency Department visits for <2 year olds and 15-20% for 6-12 month olds. The proposed studies aim to delineate the importance of HHV-6 infection in childhood by describing the epidemiology, clinical, and laboratory course associated with primary infection. The source and means of transmission of HHV-6 to the infant and whether HHV-6 persists of reactivates after primary infection in children will be determined. The extent of genetic variability among strains of HHV-6 from such children and family members will be defined. These studies will further seek to determine if neurotropic strains exist and if the human central nervous system is a site of HHV-6 persistence. Children <2 years of age presenting to the Emergency Department with acute febrile illnesses will be enrolled and examined (n=1500-1800). Blood, respiratory secretions and, when possible, cerebrospinal fluid (CSF) will be obtained for HHV-6 isolation, identification by polymerase chain reaction (PCR), and serology. An estimated 150-180 children with primary viremic HHV-6 infection will thus be identified and followed over the subsequent year to determine the clinical course and sequelae of primary HHV-6 infection and will have repeated laboratory studies to determine whether HHV-6 persists and, if so, the sites of persistent infection. Children with primary HHV-6 infection will be compared to matched children with acute illness and negative HHV-6 cultures in order to determine the distinctive epidemiology, demographics, clinical and laboratory characteristics associated with HHV-6 infection. The source and means of transmission of HHV-6 to infants with primary infection will be delineated by the study of 1) 20 pairs of mothers and their HHV-6 positive infants and 2) newborn siblings of HHV-6 positive children. These children will have long-term follow-up with serial samples of blood and respiratory secretions. Isolates of infants and family members will be compared. Genetic and phenotypic variability among and within strains of HHV-6 will be defined by identifying variable domains of the HHV-6 genome which will be used as """"""""molecular fingerprints"""""""" by two methods 1) sequence analysis of PCR-amplified DNA fragments and 2) restriction endonuclease digestive profiles of virion DNA. Whether HHV-6 strains can be divided into two groups based on antigenicity and host cell tropism will also be assessed by strain reactivity with a panel of monoclonal antibodies and by growth in various primary and continuous cell lines. Neurotropism of HHV-6 will be studied by detection of HHV-6 and/or antibody in the CSFs of children with primary of past HHV-6 infection and by PCR detection in post-mortem brain tissue of children dying of various causes, including AIDS. Neurotropic strains will be examined by using PCR to amplify directly HHV-6 gene sequences and strains compared by restriction endonuclease digestion profiles and by selective cell tropism in primary fetal neural cell types.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Epidemiology and Disease Control Subcommittee 2 (EDC)
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University of Rochester
Schools of Dentistry
United States
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Caserta, Mary T; Hall, Caroline Breese; Schnabel, Kenneth et al. (2010) Diagnostic assays for active infection with human herpesvirus 6 (HHV-6). J Clin Virol 48:55-7
Caserta, Mary T; Hall, Caroline Breese; Schnabel, Ken et al. (2007) Human herpesvirus (HHV)-6 and HHV-7 infections in pregnant women. J Infect Dis 196:1296-303
Hall, Caroline Breese; Caserta, Mary T; Schnabel, Kenneth C et al. (2006) Characteristics and acquisition of human herpesvirus (HHV) 7 infections in relation to infection with HHV-6. J Infect Dis 193:1063-9
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