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Genome Sequences Suggest Diminishing Virulence During Korean MERS Outbreak

NEW YORK (GenomeWeb) – A study appearing online today in mBio suggests that many of the Middle East respiratory coronavirus (MERS-CoV) isolates involved in a 2015 outbreak in South Korea contained mutations suspected of leading to diminished virulence in the respiratory infection-causing virus.

A team of Korean researchers used whole-genome sequencing to assess 13 MERS-CoV isolates from individuals treated at a South Korean hospital between May and July, 2015. All but one of the sequenced isolates contained point mutations expected to alter the virus' ability to bind to and infect human cells via interactions with CD26 cell surface receptors.

The study is expected to have implications for understanding MERS-CoV infections in humans, predicting future transmission patterns, and coming up with suitable vaccine strategies.

"These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26," senior author Nam-Hyuk Cho, a microbiology and immunology researcher at Seoul National University, and colleagues wrote.

More than 1,500 MERS-CoV infections have been documented since the virus was originally identified in 2012, the team noted, and the virus has a mortality rate of around 35 percent so far. A significant proportion of cases occurring so far in the Middle East and Korea have involved transmission within a healthcare setting, prompting concern that MERS-CoV may mutate to become more readily transmissible from one individual to the next.

For the new study, Cho and colleagues sought to determine whether such mutations occurred during a 2015 outbreak in Korea that infected at least 186 individuals and killed 38 individuals.

Using Sanger sequencing, they sequenced MERS-CoV isolates from respiratory secretions for 13 individuals treated at the Chungnam National University in South Korea, including one individual who had contact with the first individual infected after a trip to the Middle East and several individuals from the second, third, or fourth infection waves.

The team then analyzed the newly sequenced MERS-CoV isolates alongside two previously sequenced isolates from Korea and 99 other isolate sequences available through the GenBank database before the end of September, 2015.

Among the 26 mutations they detected in the isolates from South Korea, the researchers identified mutations in the MERS-CoV viral spike (S) protein's receptor binding domain that were introduced in isolates from the second or subsequent infection wave.

The team's predictions — supported by its preliminary experiments in a human embryonic kidney cell line — suggest such alterations lead to lower-than-usual MERS-CoV binding to human cell surface receptors, potentially decreasing over the course of the South Korean MERS-CoV outbreak.

"It is thought that human adaptation of animal coronavirus might be achieved through sequential mutations that enhance the affinity of the S protein to the human receptor," the study's authors wrote. "However, the results of our current study showing the rapid and wide spread of [a receptor binding domain] mutant with reduced affinity to human receptor generates evidence that do not support this hypothesis."