CONGENITAL CYTOMEGALOVIRUS RESEARCH

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cytomegalovirus (CMV) is the most common congenital infection in humans, affecting roughly 1% of births. While most CMV-infected infants have no symptoms at birth, approximately 10% are severly symptomatic and it is possible that up to 15% of those with no symptoms at birth will develop sensorineural hearing loss (SNHL) detectable later in childhood. Of those who are symptomatic at birth, 10% will die in infancy, and the survivors will have SNHL, mental retardation, cognitive problems, visual impairement, behavioral problems, or cerebral palsy. These variable outcomes have host and viral determinants, but no good predictive markers have been identified. Preliminary data from our laboratory suggests that polymorphisms in the human CMV-encoded TNF alpha receptor gene (UL144) appear to correlate with severe congenital CMV outcome. In a cohort of 23 congenitally infected infants, we found that CMV infection with uncommon genotypes of UL144 was highly associated with severe disease (p 0.02). Other groups have suggested a role for the amount of virus (viral loads) causing infection, with high viral loads in the amniotic fluids of mothers of infants with severe disease. We propose to determine the relative role of CMV genotypes and viral loads in the development of severe disease primarily as measured by hearing loss. We anticipate recruiting 80 patients over 2 years and following each for a minimum of 2 years (total study duration 4 years). Each subject will have 4 visits every 6 months starting at age 6 months.