When a virus jumps to humans from another species, it can seem like a supervillain bent on world domination – especially if it goes on to ignite a pandemic, as many zoonotic viruses have done in recent decades.
And yet, despite the genuine danger zoonotic pathogens pose to human civilization, they’re often just capitalizing on conditions we created, like our proximity to livestock, our degradation and invasion of wildlife habitats, and our trading of captive wildlife.
In fact, according to a new study, most of the zoonotic viruses behind recent epidemics or pandemics were surprisingly unremarkable before they jumped to humans, with no clear evidence of prior adaptive changes predisposing them for such a leap.
This challenges a common assumption about spillover events, which have long been seen as breakthroughs in which viruses leverage a novel adaptation.
Instead, the new findings suggest our spillover risk may be even greater than we thought. If spillover depends less on sudden pathogen mutations than on our encountering existing ones, we’re sitting ducks.
The study also reinforces evidence that the outbreaks examined are consistent with viruses that jumped to us from other animal hosts rather than laboratory escapes.
“This work has direct relevance to the ongoing controversy around COVID-19 origins,” says senior author Joel Wertheim, professor of medicine at the University of California, San Diego.
“From an evolutionary perspective, we find no evidence that SARS-CoV-2 was shaped by selection in a laboratory or prolonged evolution in an intermediate host prior to its emergence.
“That absence of evidence is exactly what we would expect from a natural zoonotic event – and it represents another nail in the coffin for theories invoking laboratory manipulation.”
Conventional wisdom has long suggested animal viruses need adaptive mutations before they can infect people and sustain human-to-human transmission. Given the scant evidence, Wertheim and his colleagues decided to investigate.
They examined viral genomes from outbreaks of influenza A, Ebola, Marburg, mpox, SARS-CoV, and SARS-CoV-2, focusing on the period immediately before each virus leapt to humans in hopes of identifying any adaptations that set the stage.
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 measure varying selection pressure across viral genomes at three stages: in natural animal host reservoirs; on the phylogenetic tree immediately before a spillover event; and at the beginning of sustained human outbreaks.
In all the viruses studied, natural selection intensity was normal before the leap to humans, with no detectable evolutionary signal foreshadowing spillover. Changes in selection pressure emerged only after viruses began spreading among humans.
“From a broad epidemiological standpoint, our findings challenge the idea that pandemic viruses are evolutionarily special before they reach humans,” Wertheim says.
“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 researchers further tested their approach by applying it to viruses propagated in a lab, which also helped identify distinct evolutionary signals for laboratory passage versus natural transmission.
While recent pandemics seem to mostly occur via the latter, including SARS-CoV-2, the study did find evidence consistent with laboratory origin for a different pandemic: the bizarre 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 sparked by a laboratory strain – possibly in the context of a failed vaccine trial.”
Previous research has already flagged oddities about the 1977 flu, namely a suspicious genetic similarity with H1N1 strains from the 1950s.
The new study supports the lab-escape theory in that instance alone, showing how this virus underwent selection pressure resembling that of lab-adapted flu strains and live-attenuated vaccines.
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Revisiting past pandemics can provide valuable insights that might help us thwart future ones, the researchers say.
And while lab accidents are a plausible risk, these findings suggest we’d be wise to focus more on the conditions that sparked most zoonotic diseases lately.
“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 attention where it belongs – on surveillance, prevention, and reducing the opportunities for the constant barrage of viral spillover.”
The study was published in Cell.
