The first deep sequencing method was announced in 2005. Due to an increasing number of sequencing data and a reduction in the costs of each sequencing dataset, this innovative technique was soon applied to genetic investigations of viral genome diversity in various viruses, particularly RNA viruses. These deep sequencing findings documented viral epidemiology and evolution and provided high-resolution data on the genetic changes in viral populations. Here, we review deep sequencing platforms that have been applied in viral quasispecies studies. Further, we discuss recent deep sequencing studies on viral inter- and intrahost evolution, drug resistance, and humoral immune selection, especially in emerging and re-emerging viruses. Deep sequencing methods are becoming the standard for providing comprehensive results of viral population diversity, and their applications are discussed.
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