Virus-Targeted Transcriptomic Analyses Implicate Ranaviral Interaction with Host Interferon Response in Frog Virus 3-infected Frog Tissues [article]

Yun Tian, Francisco De Jesús Andino, Jacques Robert, Yongming Sang
2021 bioRxiv   pre-print
AbstractFrog Virus 3 (FV3) is a large dsDNA virus that cause global infections in amphibians, fish and reptiles, and contribute to amphibian declines. FV3's genome contains near 100 putative open reading frames (ORFs). Previous studies have classified these coding genes into temporal classes as immediate early, delayed early and late viral transcripts based on their sequential expression during FV3 infection. To genome-wide characterize ranaviral gene expression, we performed a whole
more » ... mic analysis (RNA-Seq) using total RNA samples containing both viral and cellular transcripts from FV3-infected Xenopus laevis adult tissues using two FV3 strains, a wild type (FV3-WT) and an ORF64R-deleted recombinant (FV3-Δ64R). In samples from the infected intestine, liver, spleen, lung and especially kidney, a FV3-targeted transcriptomic analysis mapped reads spanning the full-genome coverage at ∼10× depth on both positive and negative strands. By contrast, reads were only mapped to partial genomic regions in samples from the infected thymus, skin and muscle. Extensive analyses validated the expression of almost all annotated 98 ORFs and profiled their differential expression in a tissue-, virus-, and temporal class-dependent manners. Further studies identified several putative ORFs that encode hypothetical proteins containing viral mimicking conserved domains found in host interferon (IFN) regulatory factors (IRFs) and IFN receptors. This study provides the first comprehensive genome-wide viral transcriptome profiling during infection and across multiple amphibian host tissues that will serve as instrumental reference. It also presents evidence implying that ranaviruses like FV3 have acquired previously unknown molecular mimics interfering with host IFN signaling during evolution.ImportanceFrog Virus 3 (FV3), are large dsDNA viruses that cause devastating infections globally in amphibians, fish and reptiles, and contribute to catastrophic amphibian declines. FV3's large genome encodes near 100 coding genes, of which most have been functionally uncharacterized in the viral pathogenesis. Using a whole transcriptomic analysis (RNA-Seq) in FV3-infected amphibian samples, we determined a genome-wide virus transcriptome and profiled their differential expression in a tissue-, virus-, and temporal class-dependent manners. Further studies identified several putative ORFs that encode hypothetical proteins containing viral mimicking conserved domains found in host interferon (IFN) regulatory factors (IRFs) and IFN receptors. This study provides the first comprehensive genome-wide viral transcriptome profiling during infection and across multiple amphibian host tissues that will serve as instrumental reference. It also presents evidence implying that ranaviruses like FV3 have acquired previously unknown molecular mimics interfering with host IFN signaling during evolution.
doi:10.1101/2021.04.28.441901 fatcat:5bdpqobdxrhdpgljjmm3bhmo54