Amphibious disease: rescue in sight? – How a virus could fight the deadly fungal infection in frogs

Viral helper: Frogs and toads worldwide are dying from a deadly fungal disease. But now biologists may have found an opponent to this global amphibian disease. During DNA analyzes of the fungus Batrachochytrium dendrobatidis, they discovered a virus that affects this fungus. Normally, this pathogen actually seems to accelerate the spread of the chytrid fungus. But with the help of genetic manipulation, the virus could also be converted into an antidote, as the team reports in “Current Biology”.

Amphibians worldwide are fighting against habitat loss, environmental damage and climate change. What’s more, they are being decimated by a deadly fungal disease. The amphibian disease caused by the fungus Batrachochytrium dendrobatidis – Bd for short – attacks the skin of frogs and toads, disrupting their metabolism, electrolyte balance and breathing, ultimately leading to the animals’ death.

The chytrid fungus Bd originally comes from Asia, where a new, particularly aggressive strain of the fungus emerged, among other things, as a result of the amphibian trade. This then spread rapidly across the entire world. Since then, more than 500 amphibian species have recorded a decline in population, and 90 species may even have become extinct because of the fungus. So far there is no cure for the disease.

Searching for traces in the genome of the Bd fungus

Now a remedy may be in sight: A team of scientists led by Rebecca Clemons from the University of Michigan has accidentally found a possible way to render the fungus harmless and end the amphibian pandemic. The biologists discovered a virus that can infect some strains of the fungus. So far, some fungal viruses have already been known. However, only a few of them infect the fungi that can cause diseases in animals.

Clemons and her colleagues found the virus, named BdDV-1, when they examined the genome of different populations of the Bd fungus. The biologists originally wanted to understand more precisely how the fungus developed genetically and which mutations made it so deadly to frogs and toads.

Hidden virus in the fungal genome

During the analysis, however, the researchers came across DNA sections that were not part of the fungal genome. “We realized that these additional sequences, when assembled, had the characteristics of a viral genome,” says senior author Jason Stajich of the University of California, Riverside. This was a surprising find for the biologists, as previous targeted searches for such a virus had not been successful.

But how could this virus hide so well? Unlike most viruses that attack fungi, the BdDV-1 virus does not have double-stranded RNA as its genetic material, but rather single-stranded DNA, as follow-up tests by Clemons and her colleagues showed. This means that the viral genome can be incorporated particularly well into the genome of the Bd fungus, where it is well camouflaged and was overlooked in previous studies.

Spore-forming structures of the Bd fungus. © Mark Yacoub/UCR

Virus changes the fungal infection

But what consequences does the virus attack have for the amphibian fungus? Research has shown that fungi infected with the virus behave differently than uninfected ones: “When these strains have the virus, they produce fewer spores, so the fungi spread more slowly,” says Stajich. However, this observation only applies to laboratory cultures of the fungi.

In amphibians, however, Bd fungi infected with the virus spread even faster and are even more deadly to the animals, as experiments with dwarf clawed frogs have shown. “These seemingly contradictory results have only been observed with another fungal virus,” explain the scientists. A possible explanation for this could be interactions with the immune system of the animal hosts, but also other, as yet unexplored factors.

Viral DNA as a key against the amphibian disease?

“The discovery that the chytrid fungus harbors these viruses offers the opportunity to exploit the unique biology of these viruses, for example in genetic engineering and biological control of the fungus,” state Clemons and her team. For the latter, however, the virus would have to be genetically modified in the laboratory so that it significantly inhibits or renders harmless the fungal disease in amphibians.

In order to explore these possibilities, the researchers now want to clone the virus BdDV-1, infect different strains of the Bd fungus with it and observe how they react to it. The biologists could then change the viral DNA so that the fungi produce fewer spores or the toads and frogs otherwise no longer suffer from the fungal infection and die.

To do this, however, biologists must first research and understand the virus itself better. “We don’t know how the virus infects the fungus, how it gets into the cells,” says Yacoub. “If we want to engineer the virus to help amphibians, we need answers to questions like these.” (Current Biology, 2024; doi: 10.1016/j.cub.2024.02.062)

Source: University of California-Riverside

April 5, 2024 – Claudia Krapp

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