Transmission Dynamics and Identification of Hot and Cold Spots in Coxsackievirus A16 Genome

Abstract

In the past decades, multiple outbreaks of hand, foot, and mouth disease have been recorded in Asia, with severe cases and fatalities reported in East Asian and Southeast Asian countries. Coxsackievirus A16 (CV-A16) is one of the most prevalent causative agents of hand, foot, and mouth disease. This study is the first to investigate the transmission dynamics of CV-A16 across East Asia and Southeast Asia using complete genome sequences, as well as identify the hot and cold spots in its genome. In this study, 258 isolates collected from East Asia and Southeast Asia between 1997-2019 were sourced from GenBank. The consensus (e.g. maximum likelihood) tree was constructed using RaxML. Moreover, single nucleotide variations (SNVs) were mapped using Shewhart control chart to identify the hot and cold spots. Phylogenetic analysis showed that isolates from Vietnam, Thailand, and China cluster together, while Malaysian isolates cluster with Chinese isolates. Additionally, hot spots were found on protein precursors P2 and P3, while cold spots were found in protein precursor P1. In conclusion, the study demonstrated that strains of CV-A16 were dispersed widely across East Asia and Southeast Asia, with closely related strains coming from Vietnam, Thailand, and China. Malaysian strains were also found to be closely related to Chinese strains. Additionally, hot spots were found on regions of CV-A16 genome coding for non-structural proteins, whereas cold spots were found on regions vital for capsid formation. Additional studies on spatiotemporal analysis of CV-A16, and integration of epidemiological data, virus transportation events, and up-to-date genomic data is recommended to further investigate the transmission of CV-A16.