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

Another notable nonsynonymous substitution was A107V (at position 11257), which occurred in the nonstructural protein 6 (nsp6) coding region within orf1ab. This A107V variation in nsp6 and the I529T substitution in the spike glycoprotein were frequently found in the South Korean isolates and appeared to be genetically linked ( Fig. 2; Supplemental Table S2 ). Nsp6 is a membrane-spanning protein and is an integral component of the viral replication complex involved in double-membrane vesicle formation (Lundin et al. 2014) . Although the functional importance of these MERS-CoV variants in viral replication and their interaction with the host immune system remain to be elucidated, our data showed that the selection of these variants may not be independent from each other, suggesting the unit of selection may be a combination of variants rather than individual variants.