Neonatal gammaherpesvirus-68 infection drives cardiac damage and reveals an age-dependent pathogenesis 3853

Abstract Description Gammaherpesvirus predominantly infects children early in life, yet mechanistic studies focus primarily on adult models of infection, creating a gap in understanding infection in the young. We hypothesized that early infection increases disease severity and disrupts latency establishment and maintenance. To test this, we infected C57BL/6J mice on postnatal day 3 with γ-herpesvirus-68, a model that mimics human infection. Neonatal mice exhibited a dose-dependent survival curve and higher viral loads in the spleens, lungs, and livers during acute infection compared to adults. Unlike adults, neonatal mice failed to clear acute infection and establish latency in the spleen. Neonatal peritoneal cells did establish latency similarly to adults, suggesting tissue- and cell-specific differences in latency. Ex vivo reactivation was higher in neonatal splenocytes, but not in peritoneal cells. Interestingly, we identified the heart as a unique organ of viral replication in neonates. Cardiac hematoxylin and eosin staining revealed immune infiltrates in neonates at days 4 and 9 postinfection, while adult hearts showed no infiltrates. By day 16, trichrome staining revealed neonatal cardiac fibrosis. In situ hybridization showed viral RNA in non-hematopoietic cells surrounded by B-cells on day 4 postinfection. These results demonstrate the age-dependent pathogenesis of γHV68 infection and the need for mechanistic studies to elucidate viral-induced cardiomyopathy in early life. Topic Categories Viral Immunology (VIR)