The next pandemic may not require a super-mutated virus with novel capabilities. A new study challenges long-held assumptions about how viruses jump from animals to humans, suggesting that many pandemic-causing viruses don’t undergo significant pre-adaptation before spilling over. Instead, the research indicates that human activity – our increasing proximity to animals, habitat destruction, and the wildlife trade – creates ample opportunities for existing viruses to find new hosts, making us surprisingly vulnerable to pathogens that haven’t necessarily evolved to specifically infect us.
For decades, the prevailing theory has been that zoonotic viruses, those that originate in animals and then infect humans, require specific genetic changes to overcome species barriers. These adaptations were thought to be crucial for enabling the virus to bind to human cells and replicate efficiently. Though, this new work, published in the journal Cell, suggests that this isn’t always the case. Researchers found little evidence of such pre-adaptation in the viral genomes of several pathogens that have caused recent outbreaks and pandemics, including influenza A, Ebola, mpox (formerly known as monkeypox), SARS-CoV, and SARS-CoV-2, the virus responsible for COVID-19.
Challenging the “Adapted Virus” Hypothesis
The study, led by Joel Wertheim, a professor of medicine at the University of California, San Diego, examined the genetic history of these viruses, focusing on the period immediately before they jumped to humans. Using a phylogenetic framework, the team measured the intensity of natural selection acting on the viral genomes in animal reservoirs, just before spillover, and at the start of human outbreaks. What they discovered was striking: natural selection intensity was normal before the viruses made the leap to humans. Changes in selection pressure only emerged *after* the viruses began spreading among people, suggesting that adaptation occurred in response to the new human environment, not as a prerequisite for infection.
“From a broad epidemiological standpoint, our findings challenge the idea that pandemic viruses are evolutionarily special before they reach humans,” Wertheim explained. “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.” This finding has significant implications for pandemic preparedness, shifting the focus from solely monitoring for viruses undergoing specific mutations to addressing the underlying factors that increase the risk of spillover events.
The 1977 Flu: A Case Study in Lab Origins
Interestingly, the research similarly shed light on the origins of the 1977 influenza pandemic, a particularly unusual event. The H1N1 strain that caused the pandemic was remarkably similar to strains circulating decades earlier, leading to suspicions that it originated from a laboratory. The new study provides molecular evidence supporting this theory. Researchers found that the 1977 H1N1 virus exhibited selection pressures consistent with laboratory adaptation, suggesting it may have been a strain used in vaccine development that was accidentally released.
Previous research had already highlighted anomalies surrounding the 1977 flu, including its genetic similarity to strains from the 1950s, as noted in a 2011 study published in PLoS ONE (https://doi.org/10.1371/journal.pone.0011184). Wertheim added, “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.”
Implications for COVID-19 Origins and Future Preparedness
The study’s findings also have relevance to the ongoing debate surrounding the origins of SARS-CoV-2. Wertheim and his team found no evidence that the virus was shaped by selection in a laboratory or prolonged evolution in an intermediate animal host before 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,” Wertheim stated. However, it’s essential to note that this study doesn’t definitively rule out a lab origin, but rather provides further support for a natural spillover event.
The researchers emphasize that reducing the risk of future pandemics requires a multi-faceted approach. This includes strengthening surveillance of animal populations to detect viruses with the potential to spill over, reducing human encroachment on wildlife habitats, regulating the wildlife trade, and improving biosecurity measures in laboratories. Addressing these factors is crucial, as the study demonstrates that the threat isn’t necessarily about waiting for a virus to become perfectly adapted to humans, but rather preventing the opportunities for existing viruses to make the jump in the first place.
The study’s findings underscore the importance of a “One Health” approach, recognizing the interconnectedness of human, animal, and environmental health. This collaborative, cross-disciplinary approach is essential for preventing and responding to emerging infectious diseases. The researchers plan to continue investigating the evolutionary dynamics of zoonotic viruses to better understand the factors that drive spillover events and inform public health strategies.
Looking ahead, the World Health Organization (WHO) is expected to release updated guidance on zoonotic disease surveillance and prevention in the coming months, incorporating the latest research findings. The next major checkpoint for pandemic preparedness will be the upcoming review of the International Health Regulations (IHR) in May 2024, where member states will discuss strengthening global health security frameworks.
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