A study from the University of California San Diego published in Cell reports on Mar. 9 that most animal viruses responsible for human epidemics and pandemics do not display significant evolutionary adaptation before infecting people.
This research challenges a common belief that viruses must first acquire special mutations to spread among humans. The findings suggest that many viruses may already have the ability to infect and transmit between humans, making human exposure to various animal viruses a key factor in pandemic risk.
The research team conducted a genome-wide analysis across several viral families, including influenza A virus, Ebola virus, Marburg virus, mpox virus, SARS-CoV, and SARS-CoV-2. They examined the period just before these viruses began spreading among humans but found no evidence of pre-adaptation. Instead, changes in selection pressures were only observed after sustained transmission in people had started.
"From a broad epidemiological standpoint, our findings challenge the idea that pandemic viruses are evolutionarily special before they reach humans," said Wertheim. "Rather than requiring rare, finely tuned adaptations in animals, many viruses may already possess the basic capacity to infect and transmit between humans. What matters most is human exposure to a diverse array of animal viruses."
The study also looked at historical cases such as the reemergence of H1N1 influenza A virus in 1977. Unlike other events analyzed, this strain showed signs consistent with laboratory propagation rather than natural evolution. "The 1977 influenza story is, in many ways, even more compelling than what we found for COVID-19," Wertheim said. "Our results provide new molecular evidence supporting the long-suspected idea that the H1N1 pandemic was sparked by a laboratory strain - possibly in the context of a failed vaccine trial."
Wertheim added: "This doesn't mean lab accidents don't happen. But it does mean that if a virus had been extensively passaged in a lab before an outbreak, we would expect to see it in the evolutionary record. In nearly all pandemics we've studied, that signal simply isn't there." Looking forward, Wertheim said: "Our goal is not just to understand the past, but to be better prepared for the future. By clarifying how pandemics actually begin, we can focus attention where it belongs - on surveillance, prevention and reducing the opportunities for the constant barrage of viral spillover."
