Emmie de Wit, Ph.D.

The goal of the Molecular Pathogenesis Unit (MPU) is to increase our understanding of the pathogenesis of emerging respiratory viruses on every level from host to molecule. The emergence of SARS-CoV-2 in late 2019 and the resulting COVID-19 pandemic have made clear how little we understand about the pathogenesis of viral infections of the respiratory tract and how inadequate existing therapeutics are.

Comparison of healthy lungs (left) to lungs affected by interstitial pneumonia during acute virus infection (right).

Credit: NIAID

It is important to note that even before the COVID-19 pandemic, lower respiratory tract infections were the leading cause of infectious disease deaths worldwide, and the eighth most important cause of death in the US. Besides this continuous burden of endemic respiratory viruses, emerging respiratory viruses remain an important threat to global health. Novel respiratory viruses keep emerging from animal reservoirs: in the last decade alone Middle East Respiratory Syndrome-coronavirus (MERS-CoV), enterovirus D68, Nipah virus, several avian influenza viruses, and SARS-CoV-2 emerged or re-emerged. 

Colorized electron micrograph of a SARS-CoV-2 virus particle in the lungs of an infected rhesus macaque.

Credit: NIAID

Although great progress has been made in the field of direct-acting antivirals, especially for the treatment of COVID-19, therapeutics to treat severe lower respiratory tract disease have lagged behind. A key problem in the development of treatments for severe respiratory virus disease is that virus replication often peaks ahead of disease severity. Rather than virus-induced lung damage alone, the proinflammatory immune response also contributes to severe respiratory disease. Although increasing attention is given to the host processes involved in severe respiratory infections, these studies are often hampered by a focus on in vivo pathogenesis in lethal disease models, or on mechanistic studies of single molecules or signaling pathways in vitro. In MPU, we aim to combine pathogenesis studies with detailed molecular analyses to identify molecular determinants of severe respiratory tract disease within the virus and the host. Ultimately, the identification of common pathways involved in lower respiratory tract disease progression and druggable targets within those pathways will be used to develop broad-acting, syndrome-based therapeutics.