"Insights into the Structure and Function of the OTU Protease Virulence Factors from Emerging Human Nairoviruses" ACS Infectious Diseases
Warmer temperatures bring out ticks that spread diseases such as Lyme disease and Rocky Mountain spotted fever. But another class of emerging tick-borne pathogens - nairoviruses - is on the rise. Some nairoviruses cause high fevers and reduce organ function in people exposed to certain tick's bites. In ACS Infectious Diseases, researchers report how these viruses evade the human immune system. The findings could be used to help develop a surveillance system to monitor these viruses.
This study reinforces the need to be vigilant about not just tick bites but the type of ticks that an individual has been bitten by as they may carry diseases beyond what we have been used to looking for." - Scott Pegan
"The Crimean-Congo hemorrhagic fever virus [CCHFV] represents the global danger that nairoviruses can pose to the public," says Scott Pegan, an active U.S. Army Reserve member and corresponding author of the study. This viral disease is often fatal and is a threat to civilians and U.S. service personnel serving in Africa, the Middle East and Asia. And because several newly identified nairovurses can infect humans, "advancing understanding of how these viruses skirt host immunity and using this information to develop countermeasures and biosurveillance tools just seemed right," he says.
Scientists know that some nairoviruses evade host immunity by producing a certain enzyme that makes the viruses undetectable. The enzymes remove small proteins (ubiquitin and ISG15) attached to human proteins, and without those two proteins, the immune system isn't alerted to an infection. For this study, Pegan and colleagues wanted to assess if four species of nairoviruses have enzymes that can do this.
They started by isolating enzymes from three newly identified orthonairoviruses from patients in Asia and the Pacific Coast tick nairovirus (PCTNV), which has been found in ticks but not in humans. In experiments, the enzymes showed various abilities to remove ubiquitin and ISG15 attached to human proteins, and the PCTNV enzyme performed best compared to the three other viral enzymes. These results suggest that PCTNV might be able to evade the human immune system better than other nairoviruses. Because this virus is carried by a human-biting tick already known to transmit disease (e.g., Rocky Mountain spotted fever), people along the U.S. West Coast could be at risk for exposure.
Finally, the researchers compiled enzyme activity data for ubiquitin from this and other studies, encompassing 13 nairovirus species. And they trained computer models to identify pathogenic nairoviruses, which showed early promise for developing a biosurveillance system.
"This study reinforces the need to be vigilant about not just tick bites but the type of ticks that an individual has been bitten by as they may carry diseases beyond what we have been used to looking for," concludes Pegan.
The authors acknowledge funding from the National Institutes of Health, including the National Institute of General Medical Sciences and the National Institute of Allergy and Infectious Diseases.
