Inter- and intra-host sequence diversity reveal the emergence of viral variants during an overwintering epidemic caused by dengue virus serotype 2 in southern Taiwan
Hui-Ying Ko, Yao-Tsun Li, Day-Yu Chao, Yun-Cheng Chang, Zheng-Rong T. Li, Melody Wang, Chuan-Liang Kao, Tzai-Hung Wen, Pei-Yun Shu, Gwong-Jen J. Chang, and Chwan-Chuen King
Virus genomes can show changes due to transmission between hosts. In evolutionary scale, replacements with new viral lineages are usually associated with alternating clinical burdens or epidemic potentials, but few studies have integrated viral dynamics from intra-host viral variations to macro-level clade (a monophyletic group) replacements. In this study, we combined both levels of research to study the changes in viral genomes during two consecutive dengue outbreaks (2001–2003) in southern Taiwan. We identified a potential overwintering candidate virus group characterized by lower genetic diversity, transmission rate, number of intra-host variants and a more pervasive geographical distribution pattern. Deep sequencing data revealed the temporal dynamics of minor variants in different nucleotide positions, correlated with the phylogenetic analyses of consensus sequences derived from different patients. We thus propose that investigating the quasi-species complexity of viruses from intra-host and inter-host infections can provide a novel understanding of virus evolution. Such investigations could also be a useful method to monitor the dynamics of viral changes and be included in the virological surveillance.