Study Reveals How Deadly MERS Virus Enters Human Cells

The MERS virus was first detected in humans in the year 2012 in Saudi Arabia. It is thought to have originated in camels; however it is also known that bats are carriers of a form of this virus. Since, its first detection more than 830 people have fallen due to this virus, particularly in Middle East, Europe and Asia. A couple of cases were also reported in the United States. No cure for MERS has been found till date. The disease is characterized by respiratory illness which can often lead to renal failure and it is seen 35% of the people affected by it succumb to death due to the infection.

A new research by the scientists at Cornell have revealed the details of how this virus – Middle East respiratory syndrome coronavirus (MERS-CoV) enters human cells. The finding is significant because it can help in understanding how it has the ability to infect many cells- a hallmark of viral pathogenicity. The findings will also be able to offer insights to finding new avenues for treatment.

The study first appeared online on October 6^th in the Proceedings of the National Academy of Sciences. It was also the first time the researchers used the Cornell's Biological Safety Level 3 facility that is located in the Animal Health Diagnostics Center. This was important because it allowed the study's authors, Gary Whittaker, professor of virology, and Jean Millet, a postdoctoral associate in Whittaker’s lab, to be safe while working with the live virus.

In their study, the researchers found that a common protease enzyme called furin activates the MERS-CoV with cell membrane and thus enters the host cells. It is suggested by Millet and Whittaker that if we could block furin at a specific point during the host cell entry process, a way of treating the disease could be found. This will prevent the virus from getting into the cells where it makes use of the cell's reproduction to create new viruses. It was also revealed that the coronaviruses have a spike protein that is activated by a protease and it paves way for membrane fusion and hence entry into a host cell. The place on the spike protein where a protease activates this process is known as a cleavage site. Interestingly, the researchers also discovered that there were actually two cleavage sites for the MERS virus and each of them were activated by furin at different times. First was after a new virus assembled inside the host cell and the second was when the released virus finds a new cell and is taken up into the membrane.

Another virus of the same family known as severe acute respiratory syndrome (SARS) had spread globally in the year 2003 is thought to have originated in bats and was transmitted to civets- a small mammal native to tropical Asia and Africa.

Millet, the paper’s first author remarked that the coronavirus's first characterization is that it has a spike protein containing two furin cleavage sites. His fellow researcher said that it might be that because of the extra cleavage, the virus spreads more in the animals and humans. They primarily cause infection in lungs and also infect additional cell types which include immune cells as well. This paves way for the spread of the virus throughout the body.

Millet remarked that these viruses are extremely adaptable. They mutate by changing the protease they use for activation. Their flexibility in their cleavage activation strategies makes them more difficult to interpret. It is suspected by the researchers that a MERS-CoV in camels might have mutated about two and half years ago which allowed the virus to infect humans. Presently, we know that this virus does not spread that easily between people. The chances of its spread are typically high during hospital-acquired outbreaks.

Since, people in North Africa and the Middle East have strong cultural connections to camels; they often may be exposed to raw camel products “ milk, urine “ which are thought to be main causes of infection to humans.

References

https://www.news.cornell.edu/stories/2014/10/study-reveals-how-deadly-mers-virus-enters-human-cells

https://www.sciencedaily.com/releases/2014/10/141013190354.htm