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Virus-Targeted Transcriptomic Analyses Implicate Ranaviral Interaction with Host Interferon Response in Frog Virus
Yun Tian1, Francisco De Jesús Andino2, Collins N Khwatenge1
1Department of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN 37209, USA.
Viruses
|August 10, 2021
Summary
This study reveals that Ranaviruses, like Frog Virus 3 (FV3), express nearly all their genes during infection. These viruses possess molecular mimics that interfere with the host
Area of Science:
- Virology and Molecular Biology
- Amphibian Pathology
- Transcriptomics
Background:
- Ranaviruses (family Iridoviridae) are significant pathogens causing severe disease in ectothermic vertebrates, contributing to amphibian population declines.
- Frog Virus 3 (FV3), a representative ranavirus, possesses a large genome with numerous open reading frames (ORFs) whose temporal expression patterns are incompletely understood.
- Previous research has broadly classified FV3 genes into immediate early, delayed early, and late transcripts based on sequential expression.
Purpose of the Study:
- To perform a comprehensive, genome-wide transcriptomic analysis of FV3 gene expression across multiple host tissues and viral strains.
- To identify and characterize the full spectrum of viral transcripts during infection in *Xenopus laevis*.
- To investigate potential viral mechanisms for evading host immune responses, specifically interferon (IFN) signaling.
Main Methods:
- Whole transcriptomic analysis (RNA-Seq) was conducted on total RNA from FV3-infected *Xenopus laevis* tissues (kidney, intestine, liver, spleen, lung, thymus, skin, muscle).
- Two FV3 strains were used: wild-type (FV3-WT) and a recombinant lacking ORF64R (FV3-∆64R).
- Bioinformatic analysis mapped viral reads to the FV3 genome to quantify and profile gene expression across different tissues and time points.
Main Results:
- High-depth, full-genome coverage of FV3 transcripts was achieved in kidney, intestine, liver, spleen, and lung tissues.
- Expression of almost all 98 annotated FV3 ORFs was validated, with differential expression observed depending on tissue, viral strain, and temporal class.
- Several hypothetical viral proteins were identified with conserved domains mimicking host interferon regulatory factors (IRFs) and IFN receptors.
Conclusions:
- This study presents the first comprehensive genome-wide viral transcriptome profiling during ranaviral infection in amphibian tissues.
- The findings demonstrate that ranaviruses express a vast majority of their genes and exhibit complex tissue-specific expression patterns.
- Ranaviruses have evolved molecular mimicry strategies to interfere with host IFN signaling, representing a novel mechanism of immune evasion.

