Analysis of intrapatient heterogeneity uncovers the microevolution of Middle East respiratory syndrome coronavirus

Park, Donghyun; Huh, Hee Jae; Kim, Yeon Jeong; Son, Dae-Soon; Jeon, Hyo-Jeong; Im, Eu-Hyun; Kim, Jong-Won; Lee, Nam Yong; Kang, Eun-Suk; Kang, Cheol In; Chung, Doo Ryeon; Ahn, Jin-Hyun; Peck, Kyong Ran; Choi, Sun Shim; Kim, Yae-Jean; Ki, Chang-Seok; Park, Woong-Yang

The evolutionary dynamics of RNA viruses are complex because of their high mutation rates, rapid replication rates, and large population sizes. Multiple rounds of replication of a given viral genome can generate a cloud of diverse variants or a heterogeneous viral population. Previous reports on other RNA viruses have suggested that quasispecies diversity, rather than the selection of individual variants, correlates with pathogenicity and enables adaptation to new environments (Vignuzzi et al. 2006; Lauring and Andino 2010) . The importance of characterizing viral populations as swarms with similar variants has led several groups to use next-generation sequencing (NGS) technologies on clinical samples to explore the complexity of the spectrum of mutant viruses, including HIV-1 and hepatitis B virus (Bushman et al. 2008; Eriksson et al. 2008; Margeridon-Thermet et al. 2009 ). Although the description of MERS-CoV quasispecies is far from completion, previous studies that recovered whole MERS-CoV genome sequences from dromedary camels revealed the existence of intrahost single-nucleotide variants (Briese et al. 2014; Borucki et al. 2016) .