Why did the SARS-CoV-2 virus ravage the world’s human population, when many other animal viruses did not? Using nematode worms as a model, researchers at the State of Pennsylvania conducted a series of experiments to study the factors that influence the outcome of virus spread. They found that the species of the host influences the ability of a virus to spread to a new population. For example, some species are never infected, while others are and easily transmit the virus to other individuals of the species.
“Pathogens are spreading in humans with rather alarming frequency, and a ton of terrific research has been done to determine where and when the spread is most likely,” said David Kennedy, assistant professor of biology. “However, experimentally studying the spread of a virus in the laboratory to understand the probability that a virus is transmissible to a new host is a huge challenge, especially with regard to the replication necessary to obtain scientific information. »
Clara Shaw, a Penn State postdoctoral researcher who begins a new assistant professorship at the University of Minnesota Duluth in January, noted that the worms are a powerful experimental system.
“You can have an entire population of hosts in a single petri dish, and you can fit 50 replicate populations in a space the size of a shoebox,” Shaw said. “This worm-virus system may enable the careful study needed to inform which spillover events are likely to become the next COVID-19, and which are less of a concern for human and animal health. »
To complete their study, which was published September 21 in the journal Proceedings of the Royal Society Bthe researchers used species of nematode worms of the genus Caenorhabditis. One of them, Caenorhabditis elegans (C. elegans), is commonly used in other types of biological experiments.
To first determine whether the genus Caenorhabditis would be a useful system for studying the ecology and evolution of virus host-hopping, the team examined the susceptibility of 44 species of Caenorhabditis to infection by the virus d ‘Orsay, a virus known to infect the well-studied species C. elegans, but not documented in other species. They placed small amounts of the virus on petri dishes harboring populations of different Caenorhabditis species to see if the virus might replicate. Of the 44 species tested, 14 species were susceptible to the Orsay virus.
Using these 14 species of susceptible worms, the team then assessed whether these species were able to transmit the virus by transplanting a subset of virus-exposed worms into a virus-free habitat to reproduce and potentially transmit the virus. virus to their offspring. This process was repeated to determine how long the virus was able to persist and whether it was able to persist indefinitely.
“We showed that within this genus alone, different host species displayed the full range of possible outcomes following exposure to a novel pathogen,” Kennedy said. “Some were never infected, some were infected but were unable to transmit the virus, others were infected and transmitted the virus at such low levels that the pathogen eventually disappeared , and still others have been infected and transmitted the virus well enough to sustain it indefinitely. This is the raw material needed to answer the question of why some spillover events lead to host changes and new diseases while others die out on their own without any outside intervention. . »
Specifically, the team found that host species most closely related to C. elegans – the native host of the virus – were more susceptible to infection, and hosts closely related to each other showed higher susceptibilities. similar, regardless of their relationship to C. elegans.
“These patterns of susceptibility may be because closely related hosts likely have similar receptors for virus attachment, similar environments within the host for virus navigation, and similar defenses once morest viruses,” said said Shaw.
Kennedy noted that without a good model system to study the spread of viruses, it has been difficult to understand what factors facilitate new outbreaks and how evolution takes place in emerging pathogens.
He said: “These worms can be used not only to probe the impact of ecology on spread and emergence, but also to better understand how and why patterns of spread and emergence may differ between hosts. . »
The National Science Foundation supported this research.
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