Characterization of Frog Virus 3 knockout mutants lacking putative virulence genes

Abstract To identify ranavirus virulence genes, we engineered Frog Virus 3 (FV3) knockout (KO) mutants defective for a putative viral caspase activation and recruitment domain-containing (CARD) protein (Δ64R-FV3) and a β-hydroxysteroid dehydrogenase homolog (Δ52L-FV3). Compared to wild type (WT) FV3...

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Published in:Virology (New York, N.Y.) N.Y.), 2015-11, Vol.485, p.162-170
Main Authors: Andino, Francisco De Jesús, Grayfer, Leon, Chen, Guangchun, Gregory Chinchar, V, Edholm, Eva-Stina, Robert, Jacques
Format: Article
Language:English
Subjects:
Amphibian Proteins - deficiency
Amphibian Proteins - genetics
Amphibians
Animals
CARD Signaling Adaptor Proteins - deficiency
CARD Signaling Adaptor Proteins - genetics
DNA Virus Infections - mortality
DNA Virus Infections - pathology
DNA Virus Infections - virology
Eukaryotic Initiation Factor-2 - genetics
Eukaryotic Initiation Factor-2 - metabolism
Gene Expression Regulation, Viral
Gene Knockout Techniques
Host-Pathogen Interactions
Hydroxysteroid Dehydrogenases - deficiency
Hydroxysteroid Dehydrogenases - genetics
Infectious Disease
Interferon response
Larva - virology
Mutation
Ranavirus
Ranavirus - genetics
Ranavirus - metabolism
Ranavirus - pathogenicity
Signal Transduction
Survival Analysis
Virulence
Virulence gene
Virus Replication
Xenopus
Xenopus laevis - virology
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Summary:Abstract To identify ranavirus virulence genes, we engineered Frog Virus 3 (FV3) knockout (KO) mutants defective for a putative viral caspase activation and recruitment domain-containing (CARD) protein (Δ64R-FV3) and a β-hydroxysteroid dehydrogenase homolog (Δ52L-FV3). Compared to wild type (WT) FV3, infection of Xenopus tadpoles with Δ64R- or Δ52L-FV3 resulted in significantly lower levels of mortality and viral replication. We further characterized these and two earlier KO mutants lacking the immediate-early18 kDa protein (FV3-Δ18K) or the truncated viral homolog of eIF-2α (FV3-ΔvIF-2α). All KO mutants replicated as well as WT-FV3 in non-amphibian cell lines, whereas in Xenopus A6 kidney cells replication of ΔvCARD-, ΔvβHSD- and ΔvIF-2α-FV3 was markedly reduced. Furthermore, Δ64R- and ΔvIF-2α-FV3 were more sensitive to interferon than WT and Δ18-FV3. Notably, Δ64R-, Δ18K- and ΔvIF-2α- but not Δ52L-FV3 triggered more apoptosis than WT FV3. These data suggest that vCARD (64R) and vβ-HSD (52L) genes contribute to viral pathogenesis.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2015.07.011