In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 1 ( 2021-1-19), p. e1009213-
Abstract:
Viral hemorrhagic septicemia virus (VHSV) is a rhabdovirus that causes high mortality in cultured flounder. Naturally occurring VHSV strains vary greatly in virulence. Until now, little has been known about genetic alterations that affect the virulence of VHSV in flounder. We recently reported the full-genome sequences of 18 VHSV strains. In this study, we determined the virulence of these 18 VHSV strains in flounder and then the assessed relationships between differences in the amino acid sequences of the 18 VHSV strains and their virulence to flounder. We identified one amino acid substitution in the phosphoprotein (P) (Pro55-to-Leu substitution in the P protein; P P55L ) that is specific to highly virulent strains. This P P55L substitution was maintained stably after 30 cell passages. To investigate the effects of the P P55L substitution on VHSV virulence in flounder, we generated a recombinant VHSV carrying P P55L (rVHSV-P) from rVHSV carrying P55 in the P protein (rVHSV-wild). The rVHSV-P produced high level of viral RNA in cells and showed increased growth in cultured cells and virulence in flounder compared to the rVHSV-wild. In addition, rVHSV-P significantly inhibited the induction of the IFN1 gene in both cells and fish at 6 h post-infection. An RNA-seq analysis confirmed that rVHSV-P infection blocked the induction of several IFN-related genes in virus-infected cells at 6 h post-infection compared to rVHSV-wild. Ectopic expression of P P55L protein resulted in a decrease in IFN induction and an increase in viral RNA synthesis in rVHSV-wild-infected cells. Taken together, our results are the first to identify that the P55L substitution in the P protein enhances VHSV virulence in flounder. The data from this study add to the knowledge of VHSV virulence in flounder and could benefit VHSV surveillance efforts and the generation of a VHSV vaccine.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009213
DOI:
10.1371/journal.ppat.1009213.g001
DOI:
10.1371/journal.ppat.1009213.g002
DOI:
10.1371/journal.ppat.1009213.g003
DOI:
10.1371/journal.ppat.1009213.g004
DOI:
10.1371/journal.ppat.1009213.g005
DOI:
10.1371/journal.ppat.1009213.g006
DOI:
10.1371/journal.ppat.1009213.g007
DOI:
10.1371/journal.ppat.1009213.t001
DOI:
10.1371/journal.ppat.1009213.t002
DOI:
10.1371/journal.ppat.1009213.t003
DOI:
10.1371/journal.ppat.1009213.t004
DOI:
10.1371/journal.ppat.1009213.t005
DOI:
10.1371/journal.ppat.1009213.t006
DOI:
10.1371/journal.ppat.1009213.t007
DOI:
10.1371/journal.ppat.1009213.t008
DOI:
10.1371/journal.ppat.1009213.s001
DOI:
10.1371/journal.ppat.1009213.s002
DOI:
10.1371/journal.ppat.1009213.s003
DOI:
10.1371/journal.ppat.1009213.s004
DOI:
10.1371/journal.ppat.1009213.s005
DOI:
10.1371/journal.ppat.1009213.s006
DOI:
10.1371/journal.ppat.1009213.s007
DOI:
10.1371/journal.ppat.1009213.s008
DOI:
10.1371/journal.ppat.1009213.s009
DOI:
10.1371/journal.ppat.1009213.r001
DOI:
10.1371/journal.ppat.1009213.r002
DOI:
10.1371/journal.ppat.1009213.r003
DOI:
10.1371/journal.ppat.1009213.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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