When a virus transfers from another species to humans, it can appear as though it is poised for global takeover, especially if it leads to a pandemic, as many zoonotic viruses have in recent years.
However, despite the significant threat these zoonotic pathogens pose, they are often merely responding to the environments we have created, such as our close contact with livestock, the destruction and encroachment on wildlife habitats, and the trade of captive wildlife.
A recent study reveals that most zoonotic viruses responsible for recent epidemics or pandemics were quite ordinary before infecting humans, showing no clear adaptive changes that would have made them prone to such a transition.
This finding challenges the common belief that spillover events occur when viruses develop a novel adaptation.
The new research suggests our risk of spillover might be higher than previously thought. If spillovers rely more on our exposure to existing pathogens rather than sudden mutations, we are vulnerable.
The study supports the idea that the examined outbreaks are consistent with viruses transmitted from other animal hosts rather than from laboratory settings.
“This work is directly relevant to the ongoing debate about COVID-19 origins,” says Joel Wertheim, senior author and professor of medicine at the University of California, San Diego.
“From an evolutionary standpoint, we find no evidence that SARS-CoV-2 was influenced by laboratory selection or extended evolution in an intermediate host before its outbreak.
“The lack of evidence aligns with what we would expect from a natural zoonotic event, further discrediting theories of laboratory manipulation.”
Traditionally, it has been thought that animal viruses require adaptive mutations to infect humans and sustain transmission between them. Given the limited evidence, Wertheim and his team decided to explore this further.
They analyzed viral genomes from outbreaks of influenza A, Ebola, Marburg, mpox, SARS-CoV, and SARS-CoV-2, concentrating on the period just before these viruses transitioned to humans to identify any adaptations that might have paved the way.
frameborder=”0″ allow=”accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share” referrerpolicy=”strict-origin-when-cross-origin” allowfullscreen>The researchers used a phylogenetic framework to assess selection pressure variations across viral genomes at three stages: within natural animal host reservoirs, just before a spillover event, and at the onset of sustained human outbreaks.
For all studied viruses, the intensity of natural selection was normal prior to their jump to humans, without any evolutionary signals indicating an impending spillover. Selection pressure changes were observed only after the viruses began to spread among humans.
“From a broad epidemiological viewpoint, our results challenge the belief that pandemic viruses are evolutionarily unique before reaching humans,” Wertheim says.
“Instead of requiring rare, precise adaptations in animals, many viruses may already have the basic ability to infect and transmit among humans. The key factor is human exposure to a wide range of animal viruses.”
The researchers further validated their approach by applying it to viruses grown in labs, which helped identify distinct evolutionary signals for laboratory transmission versus natural transmission.
While recent pandemics mostly appear to be naturally occurring, including SARS-CoV-2, the study did find evidence supporting a laboratory origin for a different pandemic: the unusual return of H1N1 influenza A in 1977 after a 20-year absence.
“The 1977 influenza story is, in many ways, even more compelling than what we found for COVID-19,” Wertheim says. “Our results provide new molecular evidence supporting the long-suspected idea that the H1N1 pandemic was triggered by a laboratory strain, possibly during a failed vaccine trial.”
Previous research has already flagged anomalies about the 1977 flu, particularly its genetic similarity to H1N1 strains from the 1950s.
The new study supports the lab-escape theory in this specific instance, demonstrating how this virus underwent selection pressure similar to that of lab-adapted flu strains and live-attenuated vaccines.
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Revisiting past pandemics can offer valuable insights that could help prevent future ones, according to the researchers.
While lab accidents present a plausible risk, these findings suggest a greater focus should be placed on the conditions that have led to most recent zoonotic diseases.
“Our goal is not just to understand the past, but to be better prepared for the future,” Wertheim says. “By clarifying how pandemics actually begin, we can focus efforts on surveillance, prevention, and reducing the opportunities for continuous viral spillover.”
The study was published in Cell.
