Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Kalia N
,
Hauser KA
,
Burton S
,
Hossainey MRH
,
Zelle M
,
Horb ME
,
Grayfer L
.
???displayArticle.abstract???
The global amphibian declines are compounded by infections with members of the Ranavirus genus such as Frog Virus 3 (FV3). Premetamorphic anuran amphibians are believed to be significantly more susceptible to FV3 while this pathogen targets the kidneys of both pre- and postmetamorphic animals. Paradoxically, FV3-challenged Xenopus laevis tadpoles exhibit lower kidney viral loads than adult frogs. Presently, we demonstrate that X. laevis tadpoles are intrinsically more resistant to FV3 kidney infections than cohort-matched metamorphic and postmetamorphic froglets and that this resistance appears to be epigenetically conferred by endogenous retroviruses (ERVs). Using a X. laevis kidney-derived cell line, we show that enhancing ERV gene expression activates cellular double-stranded RNA-sensing pathways, resulting in elevated mRNA levels of antiviral interferon (IFN) cytokines and thus greater anti-FV3 protection. Finally, our results indicate that large esterase-positive myeloid-lineage cells, rather than renal cells, are responsible for the elevated ERV/IFN axis seen in the tadpole kidneys. This conclusion is supported by our observation that CRISPR-Cas9 ablation of colony-stimulating factor-3 results in abolished homing of these myeloid cells to tadpole kidneys, concurrent with significantly abolished tadpolekidney expression of both ERVs and IFNs. We believe that the manuscript marks an important step forward in understanding the mechanisms controlling amphibian antiviral defenses and thus susceptibility and resistance to pathogens like FV3. IMPORTANCE Global amphibian biodiversity is being challenged by pathogens like the Frog Virus 3 (FV3) ranavirus, underlining the need to gain a greater understanding of amphibian antiviral defenses. While it was previously believed that anuran (frog/toad) amphibian tadpoles are more susceptible to FV3, we demonstrated that tadpoles are in fact more resistant to this virus than metamorphic and postmetamorphic froglets. We showed that this resistance is conferred by large myeloid cells within the tadpole kidneys (central FV3 target), which possess an elevated expression of endogenous retroviruses (ERVs). In turn, these ERVs activate cellular double-stranded RNA-sensing pathways, resulting in a greater expression of antiviral interferon cytokines, thereby offering the observed anti-FV3 protection.
R24OD030008 HHS | National Institutes of Health (NIH), P40OD010997 HHS | National Institutes of Health (NIH), IOS:1749427 National Science Foundation (NSF), P40 OD010997 NIH HHS , R24 OD030008 NIH HHS
Andino,
Characterization of Frog Virus 3 knockout mutants lacking putative virulence genes.
2015,
Pubmed
,
Xenbase
Chernyavskaya,
Loss of DNA methylation in zebrafish embryos activates retrotransposons to trigger antiviral signaling.
2017,
Pubmed
Chiappinelli,
Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses.
2017,
Pubmed
Chinchar,
Family Iridoviridae: poor viral relations no longer.
2009,
Pubmed
Chuong,
Regulatory evolution of innate immunity through co-option of endogenous retroviruses.
2016,
Pubmed
Cullen,
Experimental challenge and clinical cases of Bohle iridovirus (BIV) in native Australian anurans.
2002,
Pubmed
Demetri,
Granulocyte colony-stimulating factor and its receptor.
1991,
Pubmed
Deotare,
G-CSF-primed bone marrow as a source of stem cells for allografting: revisiting the concept.
2015,
Pubmed
Eiden,
Endogenous retroviruses--aiding and abetting genomic plasticity.
2008,
Pubmed
Estefa,
New light shed on the early evolution of limb-bone growth plate and bone marrow.
2021,
Pubmed
Frank,
Granulopoiesis in tadpoles of Rana esculenta. Ultrastructural observations on the developing granulocytes and on the development of eosinophil granules.
1989,
Pubmed
Frank,
Granulopoiesis in tadpoles of Rana esculenta. Survey of the organs involved.
1988,
Pubmed
Gantress,
Development and characterization of a model system to study amphibian immune responses to iridoviruses.
2003,
Pubmed
,
Xenbase
Grandi,
Human Endogenous Retroviruses Are Ancient Acquired Elements Still Shaping Innate Immune Responses.
2018,
Pubmed
Grau,
LTR retroelements are intrinsic components of transcriptional networks in frogs.
2014,
Pubmed
,
Xenbase
Grayfer,
Distinct functional roles of amphibian (Xenopus laevis) colony-stimulating factor-1- and interleukin-34-derived macrophages.
2015,
Pubmed
,
Xenbase
Grayfer,
Divergent antiviral roles of amphibian (Xenopus laevis) macrophages elicited by colony-stimulating factor-1 and interleukin-34.
2014,
Pubmed
,
Xenbase
Grayfer,
The amphibian (Xenopus laevis) type I interferon response to frog virus 3: new insight into ranavirus pathogenicity.
2014,
Pubmed
,
Xenbase
Grayfer,
Prominent amphibian (Xenopus laevis) tadpole type III interferon response to the frog virus 3 ranavirus.
2015,
Pubmed
,
Xenbase
Greer,
Five amphibian mortality events associated with ranavirus infection in south central Ontario, Canada.
2005,
Pubmed
Hamilton,
Colony-stimulating factors in inflammation and autoimmunity.
2008,
Pubmed
Hauser,
Amphibian (Xenopus laevis) Tadpoles and Adult Frogs Differ in Their Antiviral Responses to Intestinal Frog Virus 3 Infections.
2021,
Pubmed
,
Xenbase
Honda,
Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors.
2006,
Pubmed
Honda,
IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors.
2006,
Pubmed
Hoverman,
Anuran susceptibilities to ranaviruses: role of species identity, exposure route, and a novel virus isolate.
2010,
Pubmed
Hur,
Double-Stranded RNA Sensors and Modulators in Innate Immunity.
2019,
Pubmed
Kambol,
Complete nucleotide sequence of an endogenous retrovirus from the amphibian, Xenopus laevis.
2003,
Pubmed
,
Xenbase
Kassiotis,
Immune responses to endogenous retroelements: taking the bad with the good.
2016,
Pubmed
Kawai,
Innate immune recognition of viral infection.
2006,
Pubmed
Kim,
The mechanism of transcriptional synergy of an in vitro assembled interferon-beta enhanceosome.
1997,
Pubmed
Koubourli,
Immune roles of amphibian (Xenopus laevis) tadpole granulocytes during Frog Virus 3 ranavirus infections.
2017,
Pubmed
,
Xenbase
Landsberg,
Co-infection by alveolate parasites and frog virus 3-like ranavirus during an amphibian larval mortality event in Florida, USA.
2013,
Pubmed
Majji,
Transcriptome analysis of Frog virus 3, the type species of the genus Ranavirus, family Iridoviridae.
2009,
Pubmed
Marié,
Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7.
1998,
Pubmed
Martin,
G-CSF - A double edge sword in neutrophil mediated immunity.
2021,
Pubmed
Metzemaekers,
Neutrophil chemoattractant receptors in health and disease: double-edged swords.
2020,
Pubmed
Neely,
"Double-duty" conventional dendritic cells in the amphibian Xenopus as the prototype for antigen presentation to B cells.
2018,
Pubmed
,
Xenbase
Nicholson,
Ribonuclease III mechanisms of double-stranded RNA cleavage.
2014,
Pubmed
Reeve,
Natural stressors and ranavirus susceptibility in larval wood frogs (Rana sylvatica).
2013,
Pubmed
Robert,
Inflammation-induced reactivation of the ranavirus Frog Virus 3 in asymptomatic Xenopus laevis.
2014,
Pubmed
,
Xenbase
Rollins-Smith,
Metamorphosis and the amphibian immune system.
1998,
Pubmed
Roulois,
DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts.
2015,
Pubmed
Ryals,
A 46-nucleotide promoter segment from an IFN-alpha gene renders an unrelated promoter inducible by virus.
1985,
Pubmed
Sachs,
Insufficiency of Thyroid Hormone in Frog Metamorphosis and the Role of Glucocorticoids.
2019,
Pubmed
Santoni,
HERV-H RNA is abundant in human embryonic stem cells and a precise marker for pluripotency.
2012,
Pubmed
Swarbrick,
MECHANISMS IN ENDOCRINOLOGY: Local and systemic effects of glucocorticoids on metabolism: new lessons from animal models.
2021,
Pubmed
Tian,
Xenopus Interferon Complex: Inscribing the Amphibiotic Adaption and Species-Specific Pathogenic Pressure in Vertebrate Evolution?
2019,
Pubmed
,
Xenbase
Vogel,
Endogenous interferon production by endotoxin-responsive macrophages provides an autostimulatory differentiation signal.
1984,
Pubmed
Wendel,
Amphibian (Xenopus laevis) Tadpoles and Adult Frogs Differ in Their Use of Expanded Repertoires of Type I and Type III Interferon Cytokines.
2018,
Pubmed
,
Xenbase
Wendel,
Amphibian (Xenopus laevis) tadpoles and adult frogs mount distinct interferon responses to the Frog Virus 3 ranavirus.
2017,
Pubmed
,
Xenbase
Williams,
A decade of advances in iridovirus research.
2005,
Pubmed
Yaparla,
The unique myelopoiesis strategy of the amphibian Xenopus laevis.
2016,
Pubmed
,
Xenbase
Yaparla,
Myelopoiesis of the Amphibian Xenopus laevis Is Segregated to the Bone Marrow, Away From Their Hematopoietic Peripheral Liver.
2019,
Pubmed
,
Xenbase
Yaparla,
Differentiation-dependent antiviral capacities of amphibian (Xenopus laevis) macrophages.
2018,
Pubmed
,
Xenbase
Yaparla,
Exploring the relationships between amphibian (Xenopus laevis) myeloid cell subsets.
2020,
Pubmed
,
Xenbase
