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. Coxsackievirus B and Adenoviruses are the most common viral pathogens implicated in the development of human myocarditis, and gain entry into cells via the Coxsackie Adenovirus Receptor (CAR). Previous studies have demonstrated that expression of the murine analogue of CAR expression is higher in young versus old rodents, and that adenovirus mediated gene transduction is less efficient in aged animals. We examined CAR expression in non-human primates, using RT- PCR, immunoblot, and immunofluorescence. RNA and protein was extracted from cardiac tissue from 15 Rhesus macaque monkey of various ages (2 days-14 yrs) obtained from the Tulane National Primate Research Center (TNPRC). We determined the nucleotide sequence of the rhesus CAR (rhCAR) gene, and designed a primer-probe combination for rhCAR quantitation by real time PCR. Relative to GAPDH, rhCAR mRNA levels were inversely correlated with age in Rhesus macaques; the highest levels were seen in primates less than one year of age. Efforts to quantify relative protein expression are underway. These data suggest indicate that myocarditis and other manifestations of CVB infection in newborns may reflect higher CAR expression. Funding for preliminary studies in nonhuman primates was obtained throught the Pilot Study Program at TNPRC. Animals have been assigned, and baseline ECG, antibody levels to coxsackievirus, and echocardiograms have been obtained. Initial training for minimally invasive cardiac biopsy techniques has been completed. The first phase of the proposed studies will begin in March and will include titration of viral dose to cause disease without severe acute complications.
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