Immune and neurological outcomes of maternal-transmitted cytomegalovirus infection (P6153)

Abstract

Abstract Human cytomegalovirus (CMV) infection is the most significant infectious cause of developmental brain disorders, likely due to the predilection of the virus to infect the central nervous system early in development and that the immune system is not fully functional to eliminate this infectious agent. The data show that mother-child transmission rates for human CMV are at least 10-fold higher when mothers have their first infection while they are pregnant than if they are immune prior to becoming pregnant (30-50% versus 3%, respectively). These numbers provide a compelling argument that to prevent congenital CMV infection, all women of child-bearing age should be immune to the virus. However, immune women harbor virus in a latent state that reactivates specifically in the mammary gland during lactation, resulting in transmission of virus together with anti-viral maternal antibodies to their breastfed infants. We have established a mouse model of murine CMV infection that closely replicates this human situation. We found that neonatal mice infected while nursed by mothers with latent murine CMV infection have widespread dissemination of infectious virus, including the brain. Interestingly, the virus-specific T cell repertoire in neonates that acquire murine CMV from breast milk orally from immune mothers is distinct from neonates that ingest virus alone. The potential to elicit protective versus detrimental immune and neurological outcomes is under investigation.