The virus may be coming into contact with humans undetected.
In the long human struggle against invisible adversaries, some dangers earn their power not through force but through silence. Researchers at UC Riverside have revealed how orthonairoviruses — a family of tick-borne pathogens that includes the deadly Crimean-Congo hemorrhagic fever virus — carry specialized proteins that dismantle the body's immune alarm system before it can sound. The concern is not merely theoretical: Pacific Coast ticks already bite people across the western United States and are known to carry a related nairovirus, raising the possibility that silent, undetected infections may already be unfolding. The work, published in ACS Infectious Diseases, calls for greater vigilance at a moment when new members of this viral family continue to emerge around the world.
- Orthonairoviruses deploy proteins that strip away the body's own molecular alarm signals, allowing infection to take hold before any immune defense is triggered.
- A previously uncharacterized third function of these viral proteins has been identified — one that also appears to suppress immunity, though its mechanism remains unknown, deepening the uncertainty.
- Pacific Coast ticks already transmit multiple serious diseases to people in the western U.S., and a nairovirus has been found in the same tick species, making silent human exposure a plausible and pressing concern.
- Researchers cannot yet confirm active human infection, but the biological compatibility between these viruses and human immune systems means the absence of detected cases may reflect evasion rather than absence.
- The Nairoviridae family as a whole is expanding globally, and scientists warn that its shared immune-evasion toolkit gives the entire group significant pandemic potential requiring urgent surveillance.
Scott Pegan spent more than three decades in the U.S. Army Reserve watching tick-borne viruses remain a sharp concern in military circles even as public awareness faded. Now a biomedical sciences professor at UC Riverside, he has helped reveal how orthonairoviruses — a family that includes the notorious Crimean-Congo hemorrhagic fever virus — evade the human immune system with unsettling precision. The findings, published in ACS Infectious Diseases and selected as an Editors' Choice, suggest these pathogens may already be circulating among humans without detection.
The mechanism is molecular sabotage. Orthonairoviruses produce proteins called ovarian tumor domain proteases that target ubiquitin and ISG15 — small molecules the body uses as cellular alarm bells. By stripping these signals away, the virus keeps the immune system muted even as infection takes hold. Pegan's team also identified a third, previously unknown function of these proteins that appears to further suppress immunity, though its exact workings remain unclear.
The concern becomes local and immediate when Pacific Coast ticks enter the picture. These ticks already transmit Rocky Mountain spotted fever and other serious diseases to people across the western United States, and researchers have identified a nairovirus associated with the same species. Given how well-suited these viruses appear to be for evading human immunity, Pegan suggests that silent, unrecognized infections may already be occurring within the ticks' geographic range.
Pegan is measured in his claims — more research is needed to confirm whether the virus is actively infecting people — but he does not minimize the risk. The broader warning extends beyond any single pathogen: new orthonairoviruses are being discovered globally, each carrying the same immune-evasion toolkit, and the entire Nairoviridae family carries significant pandemic potential. For now, standard tick-bite precautions remain the practical guidance, alongside a harder truth — that some threats may already be present, circulating quietly, waiting for the science to catch up.
Scott Pegan has spent more than three decades in the U.S. Army Reserve, and in that time he watched a particular threat grow quieter in public conversation even as it remained sharp in military circles: tick-borne viruses that kill with little warning and leave few traces. Now, as a biomedical sciences professor at UC Riverside, he has helped illuminate exactly how one family of these pathogens—orthonairoviruses—manages to slip past the body's defenses so effectively. The findings, published in ACS Infectious Diseases and selected as an Editors' Choice, suggest that some of the world's most dangerous tick viruses may already be circulating among humans without detection.
Orthonairoviruses are not new. Crimean-Congo hemorrhagic fever virus, perhaps the most notorious member of the family, has caused severe hemorrhagic disease in humans for decades. But what Pegan and his team discovered is how these viruses accomplish their stealth. They produce specialized proteins called ovarian tumor domain proteases—OTUs—that function like microscopic saboteurs. These proteins target the molecular signals cells normally use to mount an immune response. Specifically, they strip away ubiquitin and ISG15, small proteins that act as cellular alarm bells. Without these signals, the body's defenses remain muted even as infection takes hold. The research identified a third function of these viral proteins that had never been characterized before, one that also appears to suppress immunity, though its exact mechanism remains unknown.
The practical concern is immediate and local. Pacific Coast ticks already transmit several serious pathogens to people in the western United States—Rocky Mountain spotted fever, Pacific Coast tick fever, and bacterial infections among them. Researchers have also identified a nairovirus associated with these same ticks. What Pegan's work suggests is that the immune-evasion machinery these orthonairoviruses possess is highly compatible with human biology. Combine that with the fact that Pacific Coast ticks are already biting people, and the implication becomes difficult to ignore: the virus may already be in contact with human populations, potentially causing infections that go unrecognized because the body cannot mount a visible immune response.
Pegan is careful not to overstate what the research proves. He emphasizes that additional work is needed to determine whether the virus is actually infecting people and causing disease. But he also does not minimize the concern. "There is a very real health concern associated with Pacific Coast tick bites," he said. The virus's ability to suppress human immunity, combined with its presence in a tick species that already transmits disease to people, creates a scenario where silent circulation becomes plausible. Future studies will need to determine whether human exposure is actually occurring within the geographic range where these ticks are found.
The broader implication reaches beyond any single pathogen. Researchers continue to identify new orthonairoviruses around the world. Each one represents a potential threat, and each one carries the same basic toolkit for evading immune detection. Pegan and his collaborators—a team that included researchers from UC Riverside and the CDC's Viral Special Pathogens Branch—argue that the rapid emergence of human-infecting orthonairoviruses, combined with their capacity to evolve and bypass immune defenses, points to significant pandemic potential within the entire Nairoviridae family.
For now, the public health response remains preventive and cautious. Pegan recommends that people continue taking standard precautions against tick bites, but he adds an important nuance: not all ticks carry the same diseases, and different species require different monitoring strategies. The research reinforces the need for continued surveillance of emerging tick-borne viruses and improved preparedness systems. It also underscores a harder truth—that some threats may already be present, circulating quietly, waiting for the science to catch up.
Notable Quotes
The virus uses these proteins to disarm the body's immune defenses at multiple stages, making it easier for the infection to take hold.— Scott Pegan, UC Riverside biomedical sciences professor
The rapid identification of human-infecting orthonairoviruses and their ability to evolve and bypass human immune defenses underscores the significant pandemic potential of the Nairoviridae family.— Scott Pegan
The Hearth Conversation Another angle on the story
Why should someone in, say, California, care about this research right now? Is there an outbreak?
Not that we know of. That's actually the unsettling part. The research suggests the virus may already be in contact with people through tick bites, but because it suppresses immune responses so effectively, infections might be going undetected. There's no outbreak—yet—but the conditions for one may already exist.
So the virus is hiding from the immune system. How does that make it more dangerous than, say, the flu?
The flu triggers obvious symptoms—fever, cough, body aches. Your immune system fights back visibly. These orthonairoviruses actively disarm that response. A person could be infected and have minimal symptoms while the virus replicates. That makes it harder to diagnose, harder to track, and easier to spread unknowingly.
The researcher mentioned Pacific Coast ticks specifically. Should people on the West Coast be alarmed?
Not alarmed, but aware. Pacific Coast ticks already transmit other serious diseases. The new finding is that they may also carry orthonairoviruses that are particularly good at evading human immunity. The risk exists, but we don't yet know how many people are actually infected or whether it's causing disease.
What would change if researchers confirmed the virus is infecting people?
Everything. Right now it's a theoretical concern backed by solid biology. If human infections are confirmed, surveillance systems would need to be set up, diagnostic tests developed, and public health agencies would need to track its spread. It could shift from a research problem to a public health emergency.
Is this a pandemic waiting to happen?
Pegan is careful about that word. He says the pandemic potential is significant, especially given how many new orthonairoviruses are being discovered globally. But pandemic requires sustained human-to-human transmission. These are tick-borne viruses. The real risk is that one of them—this one or another—could establish itself in human populations in ways we're not yet equipped to detect.