Human respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract infections in children under the age of 5, the elderly, and immunocompromised individuals, leading to millions of hospitalizations and a high mortality rate. Prior exposure to RSV affords little protection and many are susceptible to reinfection throughout life. Despite the substantial burden to global human health, there are limited effective prophylactic and therapeutic options available. The RSV genome encodes for two ORFs at the 3’ end, the multifunctional non-structural proteins NS1 and NS2. These proteins are implicated in several functions, including immune antagonism. However, the mechanisms by which NS1 and NS2 proteins modulate host responses remain incompletely defined. We recently solved the X-ray crystal structures of NS1 and NS2. Using these structures, we have advanced our understanding of non-structural protein interactions with host components. Consequences of these host-viral interactions include direct inhibition of cytosolic pathogen sensors and binding to host nuclear transcriptional machinery to shape the immune response to infection. These studies provide the basis to target NS1 and NS2 therapeutically and to generate mutant viruses that can inform on future vaccine development.

Molecular insights from RSV non-structural proteins

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.