2. Academic Validation
  3. Tiger frog virus ORF104R interacts with cellular VDAC2 to inhibit cell apoptosis

Tiger frog virus ORF104R interacts with cellular VDAC2 to inhibit cell apoptosis

  • Fish Shellfish Immunol. 2019 Sep;92:889-896. doi: 10.1016/j.fsi.2019.07.017.
Jian He 1,  Shu Mi 1,  Xiao-Wei Qin 2,  Shao-Ping Weng 2,  Chang-Jun Guo 3,  Jian-Guo He 4
Affiliations

Affiliations

  • 1 State Key Laboratory for Biocontrol / Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-sen University, No.132 Waihuan Dong Road, Higher Education Mega Center, Guangzhou, Guangdong, 510006, PR China; Southern Laboratory of Ocean Science and Engineering (Guangdong, Zhuhai), Zhuhai, 519000, China.
  • 2 Southern Laboratory of Ocean Science and Engineering (Guangdong, Zhuhai), Zhuhai, 519000, China; Institute of Aquatic Economic Animals / Guangdong Province Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, 135 Xingang Road West, Guangzhou, 510275, PR China.
  • 3 State Key Laboratory for Biocontrol / Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-sen University, No.132 Waihuan Dong Road, Higher Education Mega Center, Guangzhou, Guangdong, 510006, PR China; Southern Laboratory of Ocean Science and Engineering (Guangdong, Zhuhai), Zhuhai, 519000, China; Institute of Aquatic Economic Animals / Guangdong Province Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, 135 Xingang Road West, Guangzhou, 510275, PR China. Electronic address: gchangj@mail.sysu.edu.cn.
  • 4 State Key Laboratory for Biocontrol / Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-sen University, No.132 Waihuan Dong Road, Higher Education Mega Center, Guangzhou, Guangdong, 510006, PR China; Southern Laboratory of Ocean Science and Engineering (Guangdong, Zhuhai), Zhuhai, 519000, China; Institute of Aquatic Economic Animals / Guangdong Province Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, 135 Xingang Road West, Guangzhou, 510275, PR China.
PMID: 31299465 DOI: 10.1016/j.fsi.2019.07.017
Abstract

Ranaviruses belong to the family Iridoviridae, and have become a serious threat to both farmed and natural populations of fish and amphibians. Previous reports showed that ranaviruses could encode viral Bcl-2 family-like proteins (vBcl-2), which play a critical role in the regulation of cell Apoptosis. However, the mechanism of ranaviruses vBcl-2 interactions with host protein in mediating Apoptosis remains unknown. Tiger frog virus (TFV) belonging to the genus Ranavirus has been isolated from infected tadpoles of Rana tigrina rugulosa, and it causes a high mortality rate among tiger frog tadpoles cultured in southern China. This study elucidated the molecular mechanism underlying the interaction of TFV ORF104R with the VDAC2 protein to regulate cell Apoptosis. TFV ORF104R is highly similar to other ranaviruses vBcl-2 and host Mcl-1 proteins, indicating that TFV ORF104R is a postulate vBcl-2 protein. Transcription and protein expression levels showed that TFV orf104r was a late viral gene. Western blot results suggested that TFV ORF104R was a viral structural protein. Subcellular localization analysis indicated that TFV ORF104R was predominantly colocalized with the mitochondria. Overexpressed TFV ORF104R could suppress the release of cytochrome C and the activities of caspase-9 and Caspase-3. These results indicated that TFV ORF104R might play an important role in anti-apoptosis. Furthermore, the interaction between TFV ORF104R and VDAC2 was detected by co-immunoprecipitation in vitro. The above observations suggest that the molecular mechanism of TFV-regulated anti-apoptosis is through the interaction of TFV ORF104R with the VDAC2 protein. Our study provided a mechanistic basis for the ranaviruses vBcl-2-mediated inhibition of Apoptosis and improved the understanding on how TFV subverts host defense mechanisms in vivo.

Keywords

Apoptosis; Bcl-2; Ranavirus; TFV; VDAC2.

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