26 September 2017
A team of scientists from Saudi Arabia and Greece investigated how MERS-CoV infects a host organism and found a mechanism with which the deadly virus suppresses white blood cell responses.
MERS-CoV was first identified in humans as recently as 2012 and has infected more than 1,900 people, killing over a third of them, as of March 2017. The disease caused by the virus instigates severe respiratory tract infection, shock and multiple organ failures.
The group, spearheaded by King Faisal Specialist Hospital and Research Center immunologist Ahmed Al-Qahtani, found that the viral-surface ‘spike’ protein induces the suppression of the infected host’s immune system. It does this by binding to a specific receptor, named DPP4, on the surface of macrophages — a type of white blood cell that eliminates pathogens by engulfing and digesting them. The DPP4 receptor is also present on the cells lining the respiratory tract. The binding of the virus’s spike protein to these receptors enables the virus to adhere to and invade cells, greatly helping infection of the host.
Macrophages would usually respond to the foreign particles by releasing pro-inflammatory signaling molecules that kick-start the body’s reaction to infectious substances. The spike protein/DPP4 interaction prevents this from happening.
In their study, the team produced a mock virus that presented just the spike protein on its surface, to exclude the possibility that other interactions contributed to the resistance of the MERS-CoV. They then evaluated the effects of the MERS-CoV spike protein’s interaction with the DPP4 of isolated immune cells.
As well as its role in the survival of MERS-CoV, the DPP4 receptor is also a target for therapeutics research, says Al-Qahtani. “DPP4 is well known for its function in immune cells and DPP4 inhibitors are used as anti-diabetic drugs.”
Al-Qahtani’s team hopes their discovery will, one day, provide a significant benefit to patients infected with MERS-CoV. “Our findings provide a potential mechanism to explain why MERS-infected individuals fail to eliminate the virus as they may do with other respiratory viruses, and suggest a potential treatment to boost immune responses and anti-viral responses in infected patients,” Al-Qahtani says.
- Al-Qahtani, A.A., Lyroni, K., Aznaourova, M., Tseliou, M., Al-Anazi, M. et al. Middle east respiratory syndrome corona virus spike glycoprotein suppresses macrophage responses via DPP4-mediated induction of IRAK-M and PPARγ. Oncotarget (2017)| article