Citation: Zhuo-Cong Li, Long-Feng Lu, Can Zhang, Xue-Li Wang, Jin-Feng Tong, Ke-Jia Han, Dan-Dan Chen, Xi-Yin Li, Li Zhou, Jian-Fang Gui, Shun Li. GCRV NS38 counteracts SVCV proliferation by intracellular antagonization during co-infection .VIROLOGICA SINICA, 2023, 38(1) : 142-156.  http://dx.doi.org/10.1016/j.virs.2022.12.003

GCRV NS38 counteracts SVCV proliferation by intracellular antagonization during co-infection

  • Corresponding author: Shun Li, bob@ihb.ac.cn
  • Received Date: 10 September 2022
    Accepted Date: 07 December 2022
    Available online: 13 December 2022
  • Viral co-infection has been found in animals; however, the mechanisms of co-infection are unclear. The abundance and diversity of viruses in water make fish highly susceptible to co-infection. Here, we reported a co-infection in fish, which resulted in reduced host lethality and illustrated the intracellular molecular mechanism of viral co-infection. The spring viremia of carp virus (SVCV) is a highly lethal virus that infects Cyprinidae, such as zebrafish. The mortality of SVCV infection was significantly reduced when co-infected with the grass carp reovirus (GCRV). The severity of tissue damage and viral proliferation of SVCV was also reduced in co-infection with GCRV. The transcriptome bioinformatics analysis demonstrated that the effect on the host transcripts in response to SVCV infection was significantly reduced in co-infection. After excluding the extracellular interactions of these two viruses, the intracellular mechanisms were studied. We found that the GCRV NS38 remarkably decreased SVCV infection and viral proliferation. The interaction between GCRV NS38 and SVCV nucleoprotein (N) and phosphoprotein (P) proteins was identified, and NS38 downregulated both N and P proteins. Further analysis demonstrated that the N protein was degraded by NS38 indispensable of the autophagy receptor, sequestosome 1 (p62). Meanwhile, K63-linked ubiquitination of the P protein was reduced by NS38, leading to ubiquitinated degradation of the P protein. These results reveal that the intracellular viral protein interactions are a crucial mechanism of co-infection and influence the host pathology and expand our understanding in intracellular viral interactions co-infection.

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    GCRV NS38 counteracts SVCV proliferation by intracellular antagonization during co-infection

      Corresponding author: Shun Li, bob@ihb.ac.cn
    • a. Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China;
    • b. University of Chinese Academy of Sciences, Beijing, 100049, China;
    • c. State Key Laboratory of Freshwater Ecology and Biotechnology, Hubei Hongshan Laboratory, The Innovation Academy of Seed Design, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China;
    • d. College of Fisheries and Life Science, Dalian Ocean University, Dalian, 116023, China

    Abstract: Viral co-infection has been found in animals; however, the mechanisms of co-infection are unclear. The abundance and diversity of viruses in water make fish highly susceptible to co-infection. Here, we reported a co-infection in fish, which resulted in reduced host lethality and illustrated the intracellular molecular mechanism of viral co-infection. The spring viremia of carp virus (SVCV) is a highly lethal virus that infects Cyprinidae, such as zebrafish. The mortality of SVCV infection was significantly reduced when co-infected with the grass carp reovirus (GCRV). The severity of tissue damage and viral proliferation of SVCV was also reduced in co-infection with GCRV. The transcriptome bioinformatics analysis demonstrated that the effect on the host transcripts in response to SVCV infection was significantly reduced in co-infection. After excluding the extracellular interactions of these two viruses, the intracellular mechanisms were studied. We found that the GCRV NS38 remarkably decreased SVCV infection and viral proliferation. The interaction between GCRV NS38 and SVCV nucleoprotein (N) and phosphoprotein (P) proteins was identified, and NS38 downregulated both N and P proteins. Further analysis demonstrated that the N protein was degraded by NS38 indispensable of the autophagy receptor, sequestosome 1 (p62). Meanwhile, K63-linked ubiquitination of the P protein was reduced by NS38, leading to ubiquitinated degradation of the P protein. These results reveal that the intracellular viral protein interactions are a crucial mechanism of co-infection and influence the host pathology and expand our understanding in intracellular viral interactions co-infection.

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