'Russian nesting doll' virus hides inside a deadly fungus, making it even more dangerous to people

A fungus flagged as a "critical" concern by the World Health Organization may have a secret weapon: a virus hidden inside it.

Now, a new study suggests that targeting this virus may offer a new strategy for treating these dangerous fungal infections in people.

The virus, called A. fumigatus Polymycovirus-1 (AfuPmV-1M), was known prior to the new research. But the study revealed that the virus appears to be giving the fungus Aspergillus fumigatus several key survival advantages.

A. fumigatus can infect people who breathe in its spores. This can cause short-term or long-term lung infections or an "invasive" disease that spreads beyond the lungs. While many people breathe in Aspergillus spores every day, usually only immunocompromised patients get sick, study lead author Marina Campos Rocha, a postdoctoral researcher at the Hebrew University of Jerusalem, told Live Science. People with lung disease are also vulnerable.

The fungus is responsible for about 2.1 million cases of invasive aspergillosis and 1.8 million cases of chronic lung infection per year, out of the 6.55 million invasive fungal infections that happen worldwide each year. The invasive infection has a mortality rate that ranges from 30% to 80% worldwide.

In the new study, published Aug. 14 in the journal Nature Microbiology, scientists studied mice that they infected with A. fumigatus, which itself was infected by the AfuPmV-1M virus in what Rocha described as a "Russian doll" scenario. The fungus used was originally isolated from the lung of a patient who had died from aspergillosis.

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The researchers showed that when they gave mice antiviral drugs, the rodents' survival rate improved, they carried a lower fungal burden in their lungs, and they showed reduced viral levels compared with mice that weren't given the medicine.

In other words, by solely targeting the virus, the researchers managed to reduce the burden of the fungal infection in mice, Rocha said. This seems to disagree with findings from an earlier study, published in 2020, which found the opposite effect — that targeting the virus inadvertently worsened the fungal infection. (Rocha noted that there could be several reasons for the divergent results, including the fact that each research team used different approaches to render their fungal strains virus-free.)

Norman van Rhijn, a research fellow at the Manchester Fungal Infection Group, said the finding uncovered by Rocha and colleagues was completely novel. "This has been a big step towards understanding the virulence capacity of this fungus and has the potential to broaden these findings in other human pathogens," van Rhijn, who was not involved in the study, told Live Science in an email.

Rocha and her team found that the fungi exposed to antivirals reproduced less effectively and showed reduced melanin production; in many disease-causing fungi, melanin boosts virulence and the ability to survive in harsh environments.

The virus itself cannot harm mice or humans, since it needs specific receptors and proteins to bind to, and these are absent in the mammals, Rocha said. Each fungus-infecting virus is usually specific to one fungal species, she added.

"Like in the case of this one, it can only infect Aspergillus fumigatus," Rocha said. "It's not able to infect other fungi."

The researchers think one way the virus helps the fungus thrive is by controlling some of the processes by which the fungus processes RNA, a genetic molecule involved in making proteins. The virus somehow improves the fungus' stress responses and protein synthesis, thus strengthening survival in hostile conditions. They also saw that human immune cells found it harder to kill virus-infected strains of the fungus, compared with uninfected strains.

If the antivirals used to target AfuPmV-1M in the mice work as effectively in humans, future therapies could use the drug to weaken the fungus enough for the immune system or antifungal drugs to clear it from the body, the study authors think.

Rocha suspects other fungal pathogens that infect people may also be infected with similar viruses that boost their resilience. Together with her colleagues, she is investigating the infection mechanisms involved in infected and uninfected fungi.

"Our article represents only the initial step of this investigation," she told Live Science. "Our broader goal is to provide a more comprehensive explanation of how the process unfolds at the molecular level."