Understanding amphibian disease inside out


A Common Frog (Rana temporaria) – Photo by Bernie Kohl

In the spring of 2010, I was doing amphibian surveys among a few wetlands in Eastern Kentucky that were known for their excellent diversity. As I sauntered up to a familiar study site, I was greeted with an amphibian massacre. Hundreds of dead tadpoles floated on the surface of the wetland, creating a raft of amphibian biomass unlike anything I’d ever seen.
I was stunned. What happened?
All of the signs pointed towards an outbreak of Ranavirus, a genus of double-stranded DNA viruses that infect fish, amphibians, and reptiles. Ranavirus, right alongside the notorious fungal pathogen Batrachochytrium dendrobatidis (Bd), has been implicated in the recent, rapid decline and extinction of amphibian populations across the globe. Nasty, nasty stuff.

Ranavirus is a real bummer – Photo by Nathaniel Wheelwright

These two pathogens have been the focus of an avalanche of studies attempting to understand every aspect of their biology in order to combat the loss of native amphibians. There have been multiple solutions that lower the risk of infection, but many of these solutions are pretty darn difficult to employ in the field.
Recently, investigators have demonstrated some interesting connections between infection by Ranavirus or Bd with changes in gene expression in the host. Several studies suggest that Ranavirus infections result in adaptive immune responses in wild amphibians, and major expressional changes take place in skin tissues when animals are infected with Bd. A new study led by Stephen Price and Amber Griffiths looks for signs of differential expression among Common Frogs (Rana temporaria) infected with either Ranavirus or Bd and show that the frogs’ responses varied drastically between the two pathogens.
In the case of Ranavirus, they really didn’t do much at all:

Figure 4 from Price et al. (2015) comparing transcript counts between Bd- and Ranavirus-infected groups. Alternate false-discovery rates are displayed and following re-allocation of transcripts.

Animals infected with Bd showed five times the number of differentially expressed genes compared to those infected with Ranavirus. Differences in how these two pathogens infect and ultimately kill amphibians could certainly result in expression differences between tissues and across time periods, but the investigators still expected the animals to mount a significant immune response to Ranavirus, as other studies have shown.
However, this result underscores the dire need for species-specific understanding of how these pathogens affect populations. In the UK, where the frogs were collected, common frogs have experienced major declines due to Ranavirus infections, whereas they have shown resiliency to Bd infections. Price et al’s results provide a potential mechanism for this difference: common frogs quickly mount immune responses when infected with Bd but show a weak transcriptional response to Ranavirus.
This new paper nicely complements a similar study that appeared in Genome Biology and Evolution at the end of last year. Ellison et al tested for expression differences resulting from Bd infection among four species of central american frogs, including a species that had undergone severe declines due to Bd mortality and multiple species that have maintained stable populations in the face of Bd outbreaks. The authors showed that both Bd resistance and gene regulation vary both among and within species.
Ellison et al

Figure 1 from Ellison et al (2014) that summarizes all orthologous gene expression data (B = skin, C = spleen) among four species of frog that were infected with Bd

This entire line of research demonstrates the current and future value of transcriptomics for wildlife conservation. It is clear that only integrative pursuits that combine molecular data, ecology, natural history, and evolution will untangle the complicated web of abiotic and biotic factors that determine an individual’s, population’s, or entire species’ reaction to deadly pathogens.
It’s either that or a lot more dead frogs (and salamanders, and turtles, and fish).
Ellison, A. R., Tunstall, T., DiRenzo, G. V., Hughey, M. C., Rebollar, E. A., Belden, L. K., Harris, R.N., Ibáñez, R., Lips, K.R., & Zamudio, K. R. (2015). More than Skin Deep: Functional Genomic Basis for Resistance to Amphibian Chytridiomycosis. Genome biology and evolution, 7(1), 286-298.
Price, S. J., Garner, T. W., Balloux, F., Ruis, C., Paszkiewicz, K. H., Moore, K., & Griffiths, A. G. (2015). A de novo Assembly of the Common Frog (Rana temporaria) Transcriptome and Comparison of Transcription Following Exposure to Ranavirus and Batrachochytrium dendrobatidis. PloS one, 10(6), e0130500.

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