MULUALEM ENYEW Tilahun
$639,740
University of Virginia
Virginia
National Institute on Aging (NIA)
Summary/Abstract In light of the widespread and devastating impact of the SARS-CoV-2 pandemic, a significant number of individuals have been observed to develop chronic lung conditions characterized by persistent inflammation and fibrosis after recovering from acute COVID-19. Furthermore, recent studies indicate that such chronic lung issues are also prevalent following other respiratory viral infections, such as influenza. A critical gap in our understanding persists regarding the cellular and molecular mechanisms that underlie the development of chronic lung sequelae post-primary viral pneumonia. This gap in knowledge poses a potential obstacle in creating effective treatments for patients suffering from chronic lung fibrosis triggered by SARS-CoV-2 and other respiratory viral infections. Our research has revealed that CD8 tissue resident memory (TRM) cells exhibit high levels of the NAD+ ectoenzyme CD38. This enzyme is essential for the formation and maintenance of CD8 TRM cells after primary respiratory viral infections. In this proposal, we aim to explore the hypothesis that targeting CD38 could dampen aberrant CD8 TRM accumulation in aged hosts, thereby mitigating age-associated chronic lung fibrosis following viral pneumonia. If our hypothesis is correct, the data generated in this study will not only provide mechanistic insights as to how lung sequelae develop after viral pneumonia including COVID-19, but could also pave the way for targeted immunotherapies aiming to preserve lung function after acute viral pneumonia in the elderly.