Naturally occurring substitution in one amino acid in VHSV phosphoprotein enhances viral virulence in flounder.
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 f...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1009213 |
| _version_ | 1818735129645809664 |
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| author | Jee Youn Hwang Unn Hwa Lee Min Jin Heo Min Sun Kim Ji Min Jeong So Yeon Kim Mun Gyeong Kwon Bo Young Jee Ki Hong Kim Chan-Il Park Jeong Woo Park |
| author_facet | Jee Youn Hwang Unn Hwa Lee Min Jin Heo Min Sun Kim Ji Min Jeong So Yeon Kim Mun Gyeong Kwon Bo Young Jee Ki Hong Kim Chan-Il Park Jeong Woo Park |
| author_sort | Jee Youn Hwang |
| collection | DOAJ |
| description | 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; PP55L) that is specific to highly virulent strains. This PP55L substitution was maintained stably after 30 cell passages. To investigate the effects of the PP55L substitution on VHSV virulence in flounder, we generated a recombinant VHSV carrying PP55L (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 PP55L 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. |
| first_indexed | 2024-12-18T00:16:21Z |
| format | Article |
| id | doaj.art-88bc9afd88354ce486f67b74b5f978d0 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-18T00:16:21Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Pathogens |
| spelling | doaj.art-88bc9afd88354ce486f67b74b5f978d02022-12-21T21:27:31ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-01-01171e100921310.1371/journal.ppat.1009213Naturally occurring substitution in one amino acid in VHSV phosphoprotein enhances viral virulence in flounder.Jee Youn HwangUnn Hwa LeeMin Jin HeoMin Sun KimJi Min JeongSo Yeon KimMun Gyeong KwonBo Young JeeKi Hong KimChan-Il ParkJeong Woo ParkViral 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; PP55L) that is specific to highly virulent strains. This PP55L substitution was maintained stably after 30 cell passages. To investigate the effects of the PP55L substitution on VHSV virulence in flounder, we generated a recombinant VHSV carrying PP55L (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 PP55L 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.https://doi.org/10.1371/journal.ppat.1009213 |
| spellingShingle | Jee Youn Hwang Unn Hwa Lee Min Jin Heo Min Sun Kim Ji Min Jeong So Yeon Kim Mun Gyeong Kwon Bo Young Jee Ki Hong Kim Chan-Il Park Jeong Woo Park Naturally occurring substitution in one amino acid in VHSV phosphoprotein enhances viral virulence in flounder. PLoS Pathogens |
| title | Naturally occurring substitution in one amino acid in VHSV phosphoprotein enhances viral virulence in flounder. |
| title_full | Naturally occurring substitution in one amino acid in VHSV phosphoprotein enhances viral virulence in flounder. |
| title_fullStr | Naturally occurring substitution in one amino acid in VHSV phosphoprotein enhances viral virulence in flounder. |
| title_full_unstemmed | Naturally occurring substitution in one amino acid in VHSV phosphoprotein enhances viral virulence in flounder. |
| title_short | Naturally occurring substitution in one amino acid in VHSV phosphoprotein enhances viral virulence in flounder. |
| title_sort | naturally occurring substitution in one amino acid in vhsv phosphoprotein enhances viral virulence in flounder |
| url | https://doi.org/10.1371/journal.ppat.1009213 |
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