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

Recently, in an analysis of 13 MERS-CoV genomes associated with the 2015 outbreak in South Korea, Kim et al. (2016c) reported that 11 of those genomes had an I529T mutation in RBD, and one had a D510G mutation. The study showed that D510G and I529T mutations resulted in reduced affinity of RBD for the human CD26 receptor compared with the wildtype RBD. Based on the spread of a mutant MERS-CoV with reduced affinity for the receptor, the authors suggested that MERS-CoV adaptation during human-to-human spread might be driven by host immunological pressure such as neutralizing antibodies (Kim et al. 2016c) . Consistent with the previous analysis, our data showed that the I529T and D510G mutations were observed in the consensus sequences from 29 and 4 of 35 samples, respectively. Furthermore, our analysis at an intrapatient level showed that the frequency of the wild type at both positions was only 6.5% ± 1.7% on average, supporting a strong selection pressure favoring the variants over the wild type.