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.
