TARGETING METABOLIC REPROGRAMMING OF RESPIRATORY SYNCYTIAL VIRUS INFECTION

Abstract

Abstract Respiratory syncytial virus (RSV) causes severe respiratory disease and infects virtually most children by 2 years of age. It is the leading cause of hospitalization of infants worldwide and remerges later in life to be a serious lower respiratory tract illness in the elderly. Recently, significant emphasis focused on changes in host cellular metabolism in response to viral infection. We performed a retrospective study of pediatric patients infected with RSV and found this infection correlated with increased glucose uptake in the lungs. We characterized cells freshly isolated from naturally RSV infected pediatric patients’ nasopharyngeal aspirates (NPA) and quantified their bioenergetics. Next, we will determine RSV infection induced changes in metabolic responses of different cell types including primary human epithelial cells (NHBE), dendritic cells (DCs), macrophages (MOs) and A549 cell line. Additionally, we will characterize the infect co-cultures of NHBE and DCs/MOs with RSV to determine if their crosstalk can help regulate aberrant NHBE metabolism. We found a dramatic increase in glycolysis and mitochondria respiration in cells isolated from patients’ NPA. RSV infection increases basal respiration, ATP production, and proton leak while reducing mitochondrial oxygen consumption and respiratory capacity in pediatric patients’ NPA. Significant increases in metabolism in the infected patient’s upper respiratory cells ex vivo support our in situ findings in RSV infected patients lungs. Understanding and defining the metabolic changes in the host during RSV infection may lead to novel therapeutic approaches through targeted inhibition of specific cellular metabolic pathways.