Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Viral Hemorrhagic Septicemia Virus NV Gene Decreases Glycolytic Enzyme Gene Transcription

바이러스성 출혈성 패혈증 바이러스 NV 단백질에 의한 glucokinase 전사 활성의 억제

  • Cho, Mi Young (Pathology Research Division, National Institute of Fisheries Science) ;
  • Hwang, Jee Youn (Aquatic Disease Control Division, National Institute of Fisheries Science) ;
  • Ji, Bo Young (Aquatic Disease Control Division, National Institute of Fisheries Science) ;
  • Park, Myoung Ae (Southeast Sea Fisheries Research Institute, National Institute of Fisheries Science) ;
  • Seong, Mi So (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Kim, So Young (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Jung, Ye Eun (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Cheong, Jae Hun (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Choi, Yung Hyun (Department of Biochemistry, Dongeui University College of Korean Medicine)
  • 조미영 (국립수산과학원 병리연구과) ;
  • 황지연 (국립수산과학원 수산방역과) ;
  • 지보영 (국립수산과학원 수산방역과) ;
  • 박명애 (국립수산과학원 남동해수산연구소) ;
  • 성미소 (부산대학교 자연과학대학 분자생물학과) ;
  • 김소영 (부산대학교 자연과학대학 분자생물학과) ;
  • 정예은 (부산대학교 자연과학대학 분자생물학과) ;
  • 정재훈 (부산대학교 자연과학대학 분자생물학과) ;
  • 최영현 (동의대학교 한의과대학 생화학교실)
  • Received : 2016.10.10
  • Accepted : 2016.10.15
  • Published : 2016.12.30
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Abstract

The viral hemorrhagic septicemia virus (VHSV), which belongs to the Novirhabdovirus genus of the Rhabdoviridae family, is a viral pathogen that causes severe losses in the olive flounder farming industry. Among six encoding VHSV proteins, the non-virion (NV) protein has been shown to have an impact on virulence. In our previous studies, transcriptomics microarray analysis by using VHSV-infected olive flounder showed that VHSV infection significantly down-regulated the mRNA expression of glycolytic enzymes. In addition, VHSV NV protein variants decreased the intracellular ATP level. Based on these results, we have tried to examine the effect of VHSV NV protein on glycolytic enzyme glucokinase expression, which phosphorylates glucose to glucose 6-phosphate. Our results indicated that the NV protein significantly decreased the mRNA expression of glucokinase in olive flounder HINAE cells. Furthermore, the NV protein played a negative role in the promoter activation of glucokinase. Furthermore, glucose uptake was effectively inhibited by VHSV infection and NV protein expression in olive flounder HINAE cells. These results suggest that the VHSV NV protein negatively regulates glycolytic enzyme expression by a transcription level and eventually leads to gradual morbidity of olive flounder through cellular energy deprivation. The present results may be useful for the prevention and diagnosis of VHSV infection in olive flounder.

바이러스성 출혈성 패혈증 바이러스(VHSV)는 넙치를 포함한 어류 양식의 막대한 피해를 일으키는 바이러스 병원체이며, VHSV가 생성하는 6개의 바이러스 단백질들 중에서 NV 단백질이 병원성에 관여하는 것으로 알려져 있다. VHSV-감염 넙치를 이용한 전사체 마이크로 어레이의 선행 분석 결과에 의하면 VHSV 감염이 해당과정 효소들의 mRNA 발현을 억제함으로써 넙치 세포에서 ATP 생성을 감소시켰음을 알 수 있었다. 이들 결과를 토대로, 본 연구에서는 VHSV NV 단백질이 해당과정 효소인 glucokinase의 발현에 미치는 영향을 검토하였다. 본 연구의 결과에 의하면, NV 단백질은 넙치 세포에서 glucokinase의 mRNA 발현을 감소시켰으며, 새롭게 동정한 glucokinase의 유전자 프로모터의 활성 실험결과, NV 단백질이 glucokinase의 프로모터 활성을 저해함을 알 수 있었다. 이와 같은 작용 결과들로 인하여 VHSV NV 단백질의 발현이 세포 내로의 포도당 흡수 또한 감소시켰다. 이러한 결과들은 VHSV NV 단백질이 유전자 발현의 전사 수준에서 음성적으로 해당과정의 효소 발현을 조절함을 의미하며, 결국 세포 내 에너지의 결핍으로 넙치의 폐사로 이어질 가능성을 보여주는 것이다.

Keywords

References

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