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

2021 ◽  
Vol 12 ◽  
Author(s):  
Kelsey A. Hauser ◽  
Julia C. Singer ◽  
Muhammad Riadul H. Hossainey ◽  
Tyler E. Moore ◽  
Emily S. Wendel ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
Myeloid Cells ◽  
Amphibian Declines ◽  
Type I ◽  
Frog Virus 3 ◽  
Frog Virus ◽  
Antiviral Responses ◽  
Major Route ◽  
Susceptibility And Resistance ◽  
Insight Into

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.

Epigenetic regulation of frog innate immunity: Discovery of frog microRNAs associated with antiviral responses and ranavirus infection using a Xenopus laevis skin epithelial-like cell line

2021 ◽  
Author(s):  
Lauren A. Todd ◽  
Maxwell P. Bui-Marinos ◽  
Barbara A. Katzenback
Keyword(s):  
Xenopus Laevis ◽  
Cell Line ◽  
Antiviral Immunity ◽  
Type I Interferons ◽  
Poly I:C ◽  
Type I ◽  
Frog Virus ◽  
Interferon Stimulated Genes ◽  
Antiviral Responses ◽  
Innate Antiviral Immunity

Epigenetic regulators such as microRNAs are emerging as conserved regulators of innate antiviral immunity in vertebrates, yet their roles in amphibian antiviral responses remain uncharacterized. We profiled changes in microRNA expressions in the Xenopus laevis skin epithelial–like cell line Xela DS2 in response to poly(I:C) – an analogue of double-stranded viral RNA and inducer of type I interferons – or frog virus 3 (FV3), an immunoevasive virus associated with amphibian mortality events. We sequenced small RNA libraries generated from untreated, poly(I:C)–treated, and FV3–infected cells. We detected 136 known X. laevis microRNAs and discovered 133 novel X. laevis microRNAs. Sixty–five microRNAs were differentially expressed in response to poly(I:C), many of which were predicted to target regulators of antiviral pathways such as cGAS–STING, RIG–I/MDA–5, TLR signaling, and type I interferon signaling, as well as products of these pathways (NF–κB–induced and interferon-stimulated genes). In contrast, only 49 microRNAs were altered by FV3 infection, fewer of which were predicted to interact with antiviral pathways. Interestingly, poly(I:C) treatment or FV3 infection downregulated transcripts encoding factors of the host microRNA biogenesis pathway. Our study is the first to suggest that host microRNAs regulate innate antiviral immunity in frogs, and sheds light on microRNA–mediated mechanisms of immunoevasion by FV3.

scholarly journals Post-transcriptional regulation of frog innate immunity: discovery of frog microRNAs associated with antiviral responses and ranavirus infection using a Xenopus laevis skin epithelial-like cell line

FACETS ◽  
2021 ◽  
Vol 6 ◽  
pp. 2058-2083
Author(s):  
Lauren A. Todd ◽  
Maxwell P. Bui-Marinos ◽  
Barbara A. Katzenback
Keyword(s):  
Xenopus Laevis ◽  
Cell Line ◽  
Antiviral Immunity ◽  
Type I Interferons ◽  
Poly I:C ◽  
Type I ◽  
Frog Virus ◽  
Interferon Stimulated Genes ◽  
Antiviral Responses ◽  
Innate Antiviral Immunity

Post-transcriptional regulators such as microRNAs are emerging as conserved regulators of innate antiviral immunity in vertebrates, yet their roles in amphibian antiviral responses remain uncharacterized. We profiled changes in microRNA expressions in the Xenopus laevis skin epithelial-like cell line Xela DS2 in response to poly(I:C)—an analogue of viral double-stranded RNA and inducer of type I interferons—or frog virus 3 (FV3), an immunoevasive virus associated with amphibian mortality events. Small RNA libraries generated from untreated, poly(I:C)-treated, and FV3-infected cells were sequenced. We detected 136 known X. laevis microRNAs and discovered 133 novel X. laevis microRNAs. Sixty-five microRNAs were differentially expressed in response to poly(I:C), many of which were predicted to target regulators of antiviral pathways such as cGAS-STING, RIG-I/MDA-5, TLR signaling, and type I interferon signaling, as well as products of these pathways (NF-ĸB-induced and interferon-stimulated genes). In contrast, only 49 microRNAs were altered by FV3 infection, fewer of which were predicted to interact with antiviral pathways. Interestingly, poly(I:C) treatment or FV3 infection downregulated transcripts encoding factors of the host microRNA biogenesis pathway. Our study is the first to suggest that host microRNAs regulate innate antiviral immunity in frogs and sheds light on microRNA-mediated mechanisms of immunoevasion by FV3.

scholarly journals Prior induction of cellular antiviral pathways limits frog virus 3 replication in two permissive Xenopus laevis skin epithelial-like cell lines

2021 ◽  
Author(s):  
Maxwell P. Bui-Marinos ◽  
Lauren A. Todd ◽  
Marie-Claire D. Wasson ◽  
Brandon E. E. Morningstar ◽  
Barbara A. Katzenback
Keyword(s):  
Epithelial Cells ◽  
Xenopus Laevis ◽  
Cell Lines ◽  
Frog Skin ◽  
Poly I:C ◽  
Amphibian Skin ◽  
Amphibian Species ◽  
Frog Virus 3 ◽  
Frog Virus

Frog virus 3 (FV3) causes mortality in a range of amphibian species. Despite the importance of the skin epithelium as a first line of defence against FV3, the interaction between amphibian skin epithelial cells and FV3 remains largely uncharacterized. Here, we used newly established Xenopus laevis skin epithelial-like cell lines, Xela DS2 and Xela VS2, to study the susceptibility and permissiveness of frog skin epithelial cells to FV3, and the innate immune antiviral and proinflammatory gene regulatory responses of these cells to FV3. Both cell lines are susceptible and permissive to FV3, yet do not exhibit appreciable transcript levels of scavenger receptors recently demonstrated to be used by FV3 for cellular entry. Xela DS2 and Xela VS2 upregulate antiviral and proinflammatory cytokine transcripts in response to poly(I:C) but not to FV3 or UV-inactivated FV3. Poly(I:C) pretreatment limited FV3 replication and FV3-induced cytopathic effects in both cell lines. Thus, Xela DS2 and Xela VS2 can support FV3 propagation, represent in vitro systems to investigate antiviral responses of frog skin epithelial cells, and are novel tools for screening compounds that initiate effective antiviral programs to limit FV3 replication.

scholarly journals Molecular Insight Into the IRE1α-Mediated Type I Interferon Response Induced by Proteasome Impairment in Myeloid Cells of the Brain

2019 ◽  
Vol 10 ◽  
Author(s):  
Maja Studencka-Turski ◽  
Gonca Çetin ◽  
Heike Junker ◽  
Frédéric Ebstein ◽  
Elke Krüger
Keyword(s):  
Type I Interferon ◽  
Myeloid Cells ◽  
Interferon Response ◽  
Type I ◽  
The Brain ◽  
Insight Into

scholarly journals Prior induction of cellular antiviral pathways limits frog virus 3 replication in two permissive Xenopus laevis skin epithelial-like cell lines

2021 ◽  
pp. 104200
Author(s):  
Maxwell P. Bui-Marinos ◽  
Lauren A. Todd ◽  
Marie-Claire D. Wasson ◽  
Brandon E.E. Morningstar ◽  
Barbara A. Katzenback
Keyword(s):  
Xenopus Laevis ◽  
Cell Lines ◽  
Frog Virus 3 ◽  
Frog Virus

scholarly journals Waterborne infectivity of the Ranavirus frog virus 3 in Xenopus laevis

Virology ◽  
2011 ◽  
Vol 417 (2) ◽  
pp. 410-417 ◽  
Author(s):  
Jacques Robert ◽  
Erica George ◽  
Francisco De Jesús Andino ◽  
Guangchun Chen
Keyword(s):  
Xenopus Laevis ◽  
Frog Virus 3 ◽  
Frog Virus

scholarly journals Susceptibility of Xenopus laevis tadpoles to infection by the ranavirus Frog-Virus 3 correlates with a reduced and delayed innate immune response in comparison with adult frogs

Virology ◽  
2012 ◽  
Vol 432 (2) ◽  
pp. 435-443 ◽  
Author(s):  
Francisco De Jesús Andino ◽  
Guangchun Chen ◽  
Zhenghui Li ◽  
Leon Grayfer ◽  
Jacques Robert
Keyword(s):  
Immune Response ◽  
Xenopus Laevis ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Frog Virus 3 ◽  
Frog Virus

scholarly journals Targeted Transcriptomics of Frog Virus 3 in Infected Frog Tissues Reveal Non-Coding Regulatory Elements and microRNAs in the Ranaviral Genome and Their Potential Interaction with Host Immune Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Yun Tian ◽  
Collins N. Khwatenge ◽  
Jiuyi Li ◽  
Francisco De Jesus Andino ◽  
Jacques Robert ◽  
...  
Keyword(s):  
Regulatory Elements ◽  
Potential Interaction ◽  
Amphibian Declines ◽  
Gene Expressions ◽  
Frog Virus 3 ◽  
Frog Virus ◽  
Eukaryotic Genes ◽  
A Genome ◽  
Cold Blood ◽  
Intergenic Regions

BackgroundFrog Virus 3 (FV3) is a large dsDNA virus belonging to Ranaviruses of family Iridoviridae. Ranaviruses infect cold-blood vertebrates including amphibians, fish and reptiles, and contribute to catastrophic amphibian declines. FV3 has a genome at ~105 kb that contains nearly 100 coding genes and 50 intergenic regions as annotated in its reference genome. Previous studies have mainly focused on coding genes and rarely addressed potential non-coding regulatory role of intergenic regions.ResultsUsing a whole transcriptomic analysis of total RNA samples containing both the viral and cellular transcripts from FV3-infected frog tissues, we detected virus-specific reads mapping in non-coding intergenic regions, in addition to reads from coding genes. Further analyses identified multiple cis-regulatory elements (CREs) in intergenic regions neighboring highly transcribed coding genes. These CREs include not only a virus TATA-Box present in FV3 core promoters as in eukaryotic genes, but also viral mimics of CREs interacting with several transcription factors including CEBPs, CREBs, IRFs, NF-κB, and STATs, which are critical for regulation of cellular immunity and cytokine responses. Our study suggests that intergenic regions immediately upstream of highly expressed FV3 genes have evolved to bind IRFs, NF-κB, and STATs more efficiently. Moreover, we found an enrichment of putative microRNA (miRNA) sequences in more than five intergenic regions of the FV3 genome. Our sequence analysis indicates that a fraction of these viral miRNAs is targeting the 3’-UTR regions of Xenopus genes involved in interferon (IFN)-dependent responses, including particularly those encoding IFN receptor subunits and IFN-regulatory factors (IRFs).ConclusionsUsing the FV3 model, this study provides a first genome-wide analysis of non-coding regulatory mechanisms adopted by ranaviruses to epigenetically regulate both viral and host gene expressions, which have co-evolved to interact especially with the host IFN response.

scholarly journals Discovery of frog virus 3 microRNAs and their roles in evasion of host antiviral responses

2021 ◽  
Author(s):  
Lauren A. Todd ◽  
Barbara A. Katzenback
Keyword(s):  
Immune Responses ◽  
Cell Function ◽  
Target Prediction ◽  
Dorsal Skin ◽  
Antiviral Signaling ◽  
Frog Virus 3 ◽  
Frog Virus ◽  
Host Immune Responses ◽  
Antiviral Responses ◽  
Host Genes

Frog virus 3 (FV3, genus Ranavirus) causes devastating disease in amphibian populations and is capable of subverting host immune responses. Evidence suggests that virus-encoded microRNAs (v-miRNAs) are implicated in host immunoevasion tactics. Thus, we sought to discover FV3-encoded v-miRNAs and to uncover their putative roles in immunoevasion. Small RNA libraries were generated from FV3-infected Xela DS2, a Xenopus laevis dorsal skin epithelial-like cell line, at 24- and 72-hours post-infection (hpi). We discovered 43 FV3 v-miRNAs and identified that 15 are upregulated at 24 hpi, while 18 are upregulated at 72 hpi. Target prediction analyses revealed that FV3 v-miRNAs target host genes involved in key antiviral signaling pathways, while gene ontology analyses suggest that FV3 v-miRNAs may broadly impact host cell function. This is the first study to experimentally detect mature v-miRNAs produced by FV3. Our findings highlight the possibility that ranaviral v-miRNAs facilitate immunoevasion of frog antiviral responses.

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