Scientists have a clearer idea of how a virus that likely originated with camels can cause deadly infections in people.
There is currently no cure for MERS, a respiratory illness that can lead to renal failure and kills 35 percent of the people it infects.
Since it was first detected in humans in 2012 in Saudi Arabia, more than 830 people have fallen ill worldwide, mostly in the Middle East, Europe, and Asia, with a few cases in the United States. It may have originated in camels, though bats also carry a form of the virus.
Researchers discovered that a common protease enzyme known as furin activates the MERS-CoV (Middle East respiratory syndrome corconavirus) to fuse with cell membranes and enter host cells.
Blocking furin at a specific point in the host cell entry process could lead to a treatment by preventing the virus from getting into cells, where it uses the cell’s reproduction mechanism to make new viruses.
Coronaviruses have a spike protein that is activated by a protease and mediates membrane fusion and entry into a host cell. The location on the spike protein where a protease activates this process is called a cleavage site.
The researchers found there were two cleavage sites for MERS-CoV, each activated by furin at different times: after a new virus is assembled inside a host cell, when the virus makes its way out of the host cell to the cell surface, and again, when the released virus finds a new cell and is taken up into the membrane.
“This is the first characterization of a natural coronavirus with a spike protein containing two furin cleavage sites,” says Jean Millet, a postdoctoral associate at Cornell University and first author of the paper that is published in the Proceedings of the National Academy of Sciences.
“It might be a situation where that extra cleavage site is allowing more spread in the animal or human,” says Gary Whittaker, professor of virology.
Contact with camels
With MERS, “the primary infection is in the lungs, and even there it infects additional cell types,” including immune cells, which could allow it to spread throughout the body.
One way viruses mutate is by changing the protease they use for activation. “This study shows how flexible coronaviruses are in terms of cleavage activation strategies,” says Millet. “They are extremely adaptable.”
Researchers suspect that a MERS-CoV in camels may have mutated two and half years ago, allowing the virus to infect humans. At present, the virus does not spread easily between people, except during hospital-acquired outbreaks.
Societies in North Africa and the Middle East have strong cultural connections to camels, where “there are a lot of activities that expose people to raw camel products—milk, urine—which could be the root of infection to humans,” says Whittaker.
Another coronavirus in the same family as MERS-CoV is severe acute respiratory syndrome (SARS), which spread globally in 2003. SARS appears to have originated in bats, and was transmitted to civets, a small mammal native to tropical Asia and Africa.
The National Institutes of Health funded the work.
Source: Cornell University