Poster #58 - Marco DiGialleonardo

Using novel c/μ method to predict adaptive mutations in Respiratory Syncytial Virus A

Marco DiGialleonardo 1 Chun Wu, Ph.D. 1,2 1 Department of Biological and Biomedical Sciences, Rowan University, Glassboro, NJ 08028, USA 2 Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ 08028, USA

Respiratory Syncytial Virus A (RSV-A) is a leading cause of respiratory infections in infants, young children, and elderly. While there has been progress in developing RSV vaccine and monoclonal antibody treatments, RSV-A remains a global health threat due to immune escape mutations. To solve this, a novel substitution-mutation rate ratio (c/μ) method, which was tested on SARS-CoV-2 (COVID-19) and human immunodeficiency virus (HIV) empirical sequence data, will be used to identify adaptive mutations across the RSV-A genome and characterize its molecular evolution. The c/μ method quantifies the relationship between the substitution rate (c) and predicted mutation rates (μ), where μ is independent of selection, time, and genomic location. c/μ was applied to the entire RSV-A genome, including the Translated Region (TR), Untranslated Region (UTR) and four-fold degenerate sites. Using this method, we identified 109 nonsynonymous mutations under adaptive selection (c/μ > 1); of the 30/109 mutations supported by literature mutation effects, 10/30 had confirmed adaptive mutation effects. Most of the adaptive mutations were concentrated in the Glycoprotein (G) and Fusion (F) protein, both of which are current or potential vaccine and drug targets. Notable mutations such as N276S and K124N in the F protein, and E232G, P226L, and P274L in the G protein, appear to promote viral binding to host cells and aid immune evasion. Full-length structural modeling of the G and F proteins will be used to map out and mark the adaptive mutations as potential drug targets. Additionally, an L-shaped c/μ distribution of fitness effects alongside variable presence of molecular clock was observed across its genome and genomic segments, suggesting RSV-A follows Near Neutral Selectionist Theory, contrasting conventional neutralist and selectionist theories. These findings support the use of c/μ as a predictive framework for identifying relevant mutations in viruses.