Health and Medicine
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Early in a viral disease outbreak, it could be just as important to look at exactly who is getting infected, as well as how many people and what their symptoms are. That’s because some people may act as what scientists are calling “evolutionary accelarators”, inadvertently providing the virus with the perfect conditions to develop new mutations that make it more virulent.
The rest of this article is behind a paywall. Please sign in or subscribe to access the full content.To be clear, we’re not sure yet if this actually happens in human populations, in a real-world setting like a pandemic. But new research led by scientists at the University of Utah has demonstrated it in mice, making it a theoretical possibility worth exploring further.
Genetic factors within the host organism, as well as its sex, can strongly impact how a virus evolves while it is infecting them. If the earliest patients in a pandemic scenario have the right combination of these factors, we could be looking at a kind of incubator of viral virulence.
“Some hosts seem to select for virulence-associated mutations, virulence traits that affect other hosts as well. This supports the idea that if a virus infects them, then it’ll become worse for the entire population. We don’t know this yet, but it’s what our work indicates that could be happening,” said co-author Rodrigo Costa in a statement.
The team used an H3N2 influenza A virus that they adapted to infect mice. It was the same strain that caused the “Hong Kong” flu pandemic, which raged between 1968 and 1970 and caused up to 4 million deaths.
You probably don’t need a reminder that flu pandemics have been historically devastating – the 1968 pandemic paled in comparison to the 1918-19 one – and that many experts are concerned that another could be coming with the multi-species outbreaks of H5N1 that have been hitting the headlines.
In total, they ended up with 28 different viral lineages, after evolving the virus separately in male and female mice from two different lab strains.
“At the beginning of a pandemic, the virus comes from some animal and infects a new host species, where it acquires mutations that allow it to replicate faster. And that’s what we’re seeing with our experimental work. It’s emulating that first wave of infection and that first time a virus sees a population of new hosts,” said Costa.
The mice were then infected in 10 cycles while the virus’s replication and evolution were observed, as well as how the mice were doing. The team used a cutting-edge technique to track, in 3D, which specific parts of viral proteins were hotspots of selection.
In some hosts, they observed the virus gaining mutations that made it more virulent. Infections in the female mice of one strain produced more mutations than the males; infections in the other strain of mice produced fewer mutations overall. Both host sex and host genetics, therefore, have the potential to shape influenza virus evolution in a way that could have knock-on impacts for the rest of the population.
“These revelations are often unpredictable,” explained principal investigator Wayne Potts, a professor of biology at the University of Utah. “For example, when we designed these experiments, our favored hypothesis was that increased viral genetic diversity – via inoculations of viruses collected and mixed from multiple infected hosts – would be a major factor influencing virulence evolution, something we also tested.
“There was some support for this hypothesis, but it was minor compared to the influence of host sex and genotype and the observation that more resistant hosts select for greater viral virulence.”
It’s too early to say whether this effect can even be seen in humans, let alone whether it has influenced the trajectories of pandemics past, or could in the future.
“These are mice, not humans, but if the idea that different sexes and genotypes affect the evolution of the virus differently is true, this can be used, for example, to inform disease control strategies where the individuals or groups more likely to select for virulence get vaccinated first,” said Costa.
“If we found that this is also true in humans, then in the future, with enough sequencing data and more knowledge of these interactions and what these proteins do, maybe we can predict which hosts will be more likely to make the virus more virulent and immunize those people first.”
The study is published in the journal Nature Communications.
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