Subtle differences determine risk from MERS strains

MERS-CoV first made the leap from dromedary camels to humans in 2012. Since then, this virus has been responsible for nearly 900 deaths , largely due to isolated super spreader events on the Arabian Peninsula. The family of viruses responsible for that initial outbreak has essentially disappeared, but two other major MERS-CoV families known as clade B and clade C have continued to circulate extensively in camels in the Middle East and Africa, respectively. 

No MERS outbreaks have occurred in Africa to date, indicating that clade C viruses are less adapted for infecting human lung tissue. To test this hypothesis, Peiris, Mok and colleagues teamed up with other researchers across Africa to collect dozens of camel-derived clade C viruses and compare them with their Arabian counterparts. 

Strikingly, these African MERS-CoV strains consistently showed much poorer replication in both human lung tissue and humanized mouse models . “I found it very surprising that the two clades of viruses appear to behave differently in humans although they are more than 99% identical at the genetic level,” says Peiris. Closer analysis of the various viruses revealed subtle but important sequence and structural changes in the MERS-CoV spike  protein that reduce the ability of clade C viruses to bind and enter lung cells. 

Ghazi Kayali , who oversees coronavirus research and surveillance through the Lebanon-based NGO Human Link,  says the work is an important step toward understanding the features that determine MERS-CoV pathogenicity. Although outbreaks are currently rare, the camel trade could introduce more dangerous clade B strains into Africa, whereas domestic clade C strains could likewise acquire the ability to better infiltrate human cells. “Mutations are already taking place,” says Kayali, who was not involved in the study, “and there's a very, very strong possibility that one of these mutations can lead to a problem.”

Careful monitoring will be essential for intercepting such spillover events, and Peiris notes that such surveillance is sorely lacking at present. “We need more surveillance and characterization of the virus in camels, and also for respiratory disease in camel herding populations in Africa,” he says.

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