Amphibian (Xenopus laevis) Tadpoles and Adult Frogs Differ in Their Antiviral Responses to Intestinal Frog Virus 3 Infections

Abstract

The global amphibian declines are compounded by ranavirus infections such as Frog Virus 3 (FV3), and amphibian tadpoles more frequently succumb to these pathogens than adult animals. Amphibian gastrointestinal tracts represent a major route of ranavirus entry, and viral pathogenesis often leads to hemorrhaging and necrosis within this tissue. Alas, the differences between tadpole and adult amphibian immune responses to intestinal ranavirus infections remain poorly defined. As interferon (IFN) cytokine responses represent a cornerstone of vertebrate antiviral immunity, it is pertinent that the tadpoles and adults of the anuran Xenopus laevis frog mount disparate IFN responses to FV3 infections. Presently, we compared the tadpole and adult X. laevis responses to intestinal FV3 infections. Our results indicate that FV3-challenged tadpoles mount more robust intestinal type I and III IFN responses than adult frogs. These tadpole antiviral responses appear to be mediated by myeloid cells, which are recruited into tadpole intestines in response to FV3 infections. Conversely, myeloid cells bearing similar cytology already reside within the intestines of healthy (uninfected) adult frogs, possibly accounting for some of the anti-FV3 resistance of these animals. Further insight into the differences between tadpole and adult frog responses to ranaviral infections is critical to understanding the facets of susceptibility and resistance to these pathogens.

A perspective into the relationships between amphibian ( Xenopus laevis ) myeloid cell subsets

“…Frog kidneys are a central site of FV3 replication [34][35][36]. Compared to control animals, we observed a non-significant trend towards lower kidney FV3 DNA loads in the kidneys of recombinant IL34-pretreated frogs and towards higher kidney FV3 DNA loads in recombinant FT3L-treated frogs (electronic supplementary material, figure S2).…”

Endogenous Retroviruses Augment Amphibian (Xenopus laevis) Tadpole Antiviral Protection

“…We showed recently that tadpoles respond to intestinal FV3 infections by recruiting esterase-positive, IFN-expressing, and IL-34-dependent mononuclear phagocytes into this tissue (7). Considering that in addition to polymorphonuclear granulocytes, the CSF3 receptor (CSF3R) is also expressed on mammalian monocytes (42) and X. laevis IL-34-macrophages (43), we anticipate that the presently described rCSF3-responsive mononuclear phagocytes residing within the tadpole kidneys share features with the frog antiviral IL-34-macrophages.…”

The amphibian immune system

“…42 genes in X. laevis and 51 genes in X. tropicalis ) including both intron-spanning and intron-less genes that cannot be confidently classified as alpha or beta by phylogenetic study (reviewed in [43]). Xenopus type III IFNs also comprise an expanded set of fish-like intron-containing and mammalian-like intronless genes [44]. To date amphibians are the only class known to have both intron containing and intron-less IFN genes [45].…”