Viruses have the potential to cause enormous health, social, and economic burdens. These burdens are demonstrated by influenza viruses, which cause seasonal epidemics, and SARS-CoV-2 viruses, which caused the ongoing COVID-19 pandemic resulting in over 4.55 million deaths. Virus research and vaccine strain selection often require viruses to be propagated in cell lines or embryonated chicken eggs. However, viruses may acquire culture-adapted mutations during this process, biasing our understanding of the viruses and consequently affecting disease prevention and control strategies. We determined whether culture-adaptations occur during influenza B virus (IBV) and SARS-CoV-2 virus propagation and their phenotypic implications. To do this, we collected nasopharyngeal swab samples from individuals experiencing influenza-like illnesses during the 2019-2020 influenza season and those who tested COVID-19-positive during 2020 in Columbia, Missouri. These viruses were isolated and whole genome sequencing was performed on both original samples and isolates to identify culture adaptations. We found that culture adapted mutations occurred in seasonal IBVs across multiple genes including the hemagglutinin surface glycoprotein and the RNA polymerase complex. We also identified culture adaptations within the spike gene of SARS-CoV-2 that facilitated their replication ability. This knowledge may help optimize strategies for disease surveillance, prevention, and control as well as vaccine strain selection and vaccine development.
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