Genetic symphony: investigating codon usage bias and evolutionary dynamics in West Nile virus across diverse geographical regions

INTRODUCTIONWest Nile virus (WNV) is a mosquito-borne zoonotic disease belonging to the Flavivirus genus within the Flaviviridae family, which includes over 75 viral species.It was initially identified in 1937 in Uganda, Africa, and has since spread globally, impacting Europe, North America, the Middle East, and West Asia [1,2].The virus circulates between mosquitoes and birds but can also affect mammals such as horses and humans.Since the mid-1990s, WNV outbreaks have grown in severity, frequency, and geographical range, driven by increasing prevalence of mosquito vectors [3].After the propagation of the ABSTRACT: West Nile Virus (WNV) infection, a significant zoonotic disease caused by Flaviviruses, affects birds, humans, and other wildlife species, leading to mild to severe fever and sometimes fatal neuroinvasive disease.Since its discovery, WNV has triggered epidemics on every continent except Antarctica, leading to significant financial losses from treatment costs, control programs, and the loss of animals and their products.The absence of specialized antiviral therapies or effective vaccines contributes to ongoing outbreaks in both endemic and non-endemic regions.This study combines analyses of codon usage bias, evolutionary dynamics, and phylogeography of WNV across Africa, America, Asia, and Europe.Results indicate that mutational pressure and natural selection shape codon usage bias, with natural selection being the primary driving force.Evolutionary dynamic analysis identified Uganda (Africa), China (Asia), Connecticut (United States of America), and Russia (Europe) as significant regions, with the tMRCA dated to 1908, 1785, 1852, and 1785, respectively.The highest evolutionary rate was observed in America, with a mean rate of 6.498E-2.These findings highlight key regions and evolutionary mechanisms driving WNV spread, essential for targeted surveillance and intervention.The study informs the development of specialized antiviral therapies and vaccines to mitigate WNV outbreaks globally.