UC Riverside Identifies How Tick Borne Viruses Evade Immunity

A study led by a University of California, Riverside biomedical scientist shows how a family of tick-borne viruses known as orthonairoviruses can evade immune defenses, offering important insights into emerging infectious disease threats and the potential pandemic risk posed by these viruses.

Orthonairoviruses include some of the world's most dangerous tick-borne pathogens, such as Crimean-Congo hemorrhagic fever virus, which can cause severe hemorrhagic disease in humans. The research focuses on specialized viral proteins called ovarian tumor domain proteases, or OTUs, which help these viruses suppress the body's immune response.

My inspiration for working on orthonairoviruses came from two passions. One was a longstanding scientific interest in how viruses manipulate the host immune system. The other was my desire to help fellow soldiers. During my more than 30 years in the U.S. Army Reserve, I became increasingly aware of the threat these viruses pose to service members and the public."

Scott Pegan, Professor of Biomedical Sciences, University of California, Riverside

The study, published in ACS Infectious Diseases and featured as an ACS Editors' Choice, examined how viral OTUs interfere with critical cellular communication pathways that help the body detect and fight infection. Normally, cells use small proteins called ubiquitin and ISG15 to regulate immune responses. OTUs can remove these molecular signals, effectively blunting the body's defenses.

"The virus uses these proteins to disarm the body's immune defenses at multiple stages, making it easier for the infection to take hold," Pegan said. "Our study also highlights a third, previously uncharacterized function of these viral proteins that appears to contribute to immune evasion. Its function is not known."

Researchers continue to identify new orthonairoviruses around the world. In the United States, the Pacific Coast tick is already known to transmit several serious bacterial and viral pathogens, including those responsible for Rocky Mountain spotted fever and Pacific Coast tick fever. Previous studies have also identified a nairovirus associated with these ticks.

The findings contribute to a growing body of research aimed at understanding how emerging viruses interact with the immune system and may inform the future development of diagnostics, surveillance tools, and medical countermeasures.

"There is a very real health concern associated with Pacific Coast tick bites," Pegan said. "Our work demonstrates that one of the Pacific Coast tick orthonairovirus mechanisms used to suppress host immunity is highly compatible with humans. Combined with the fact that this virus is carried by a tick species that already transmits disease to people, it suggests the virus may be coming into contact with humans and could potentially be circulating undetected."

Pegan cautioned that additional research is needed to determine whether the virus is infecting people and causing disease. He said future studies are needed to help researchers determine whether human exposure is occurring within the tick's geographic range.

"People should continue taking steps to avoid tick bites," Pegan said. "Our research reinforces the importance of paying attention not only to tick exposure but also to the type of tick involved, because different species may carry diseases that we're not yet routinely monitoring."

The research also highlights the need for continued surveillance of emerging tick-borne viruses and improved preparedness for future outbreaks.

"If there is one thing people should take away from this study, it is that the rapid identification of human-infecting orthonairoviruses and related viruses, combined with their ability to evolve and bypass human immune defenses, underscores the significant pandemic potential of the Nairoviridae family," Pegan said.

Pegan was joined in the study by UCR researchers Adam Godzik, Lukasz Jaroszewski, David S. Gonzalez, Amritpal Jalf, Vanessa Moresco, Joseph Garcia, David Matta, Jonathan Nguyen, and Bryan Torres; as well as Éric Bergeron from the Viral Special Pathogens Branch, Centers for Disease Control and Prevention.

The research was funded by National Institute of Allergy and Infectious Diseases and National Institute of General Medical Sciences.

The title of the paper is "Insights into the Structure and Function of the OTU Protease Virulence Factors from Emerging Human Nairoviruses."