In 2015, an unexpectedly large outbreak of Middle East Respiratory Syndrome coronavirus (MERS-CoV) in South Korea had a disastrous impact on the whole country and highlighted scientists limited knowledge of this virus. Now, new research into this outbreak has revealed some very surprising findings.
MERS-CoV was first identified in Saudi Arabia in 2012. The virus has been mainly seen in Middle Eastern countries, with cases reported in at least 10 other countries in Europe, Asia, and the United States. The virus causes severe respiratory infection and has a worldwide mortality rate of approximately 35%. Similar to other coronaviruses, MERS-CoV utilizes a large surface spike glycoprotein to enter human CD26 cells and cause infection.
From May to July 2015, a large outbreak of MERS initiated by an infected traveler from the Arabian peninsula swept South Korea. In its wake, it left 186 confirmed cases and 38 deaths. “The unexpected outbreak raised strong concerns about the possible generation of mutant viruses and prompted us to investigate the MERS viruses infecting Korean patients,” said Nam Hyuk Cho, PhD, faculty member at the Seoul National University College of Medicine in Korea, and principal investigator of a new study reported this week in mBio, an online open-access journal of the American Society for Microbiology.
In the study, investigators isolated 13 new viral genomes from 14 infected patients with MERS treated during the outbreak. They found that 12 of the genomes had two specific point mutations (I529T and D510G mutations) in the receptor-binding domain (RBD) of the viral spike protein. Further analysis showed that the acquired mutations made the virus less virulent rather than more virulent.
“Strikingly, both mutations resulted in reduced affinity of RBD to human CD26 compared to wild-type RBD,” explained Dr. Cho. “This is an interesting strategy of coronavirus evolution to survive in nature and live together with the new host. The virus may tune down its power to attack for the sake of longer survival in the new host.”
Dr. Cho pointed out that the kinds of changes seen in the viral spike protein have been reported previously in the study of severe acute respiratory syndrome. (SARS)-CoV, another animal-derived coronavirus that spread worldwide in 2002 and 2003. At that time, scientists said changes in the spike protein toward reduced affinity to the human CD26 receptor might be driven by immunological pressure, such as neutralizing antibodies. Neutralizing antibodies defend a cell from an antigen or infectious body by neutralizing any effect it has biologically. “This type of viral evolution during host changes, camel-to-human and human-to-human spread, may occur for host adaptation and immune escape,” said Dr. Cho. “The mutations may impair viral fitness and virulence to human, but provide more of a chance to escape the antiviral immunity.”
The findings have implications for the development of a vaccine for MERS. Currently, most vaccine trials for MERS prevention are using the spike antigen to generate effective neutralizing antibodies against it. “Strategies for vaccine development also need to consider the chance of emergence of neutralizing antibody-escape mutants,” said Dr. Cho. “Vaccines for MERS need to target the more stable and conserved region of the spike.”
-- Kate O'Rourke