2. Academic Validation
  3. Pseudorabies virus hijacks the Rab6 protein to promote viral assembly and egress

Pseudorabies virus hijacks the Rab6 protein to promote viral assembly and egress

  • Vet Res. 2024 May 28;55(1):68. doi: 10.1186/s13567-024-01328-4.
Dong-Ge Liang # 1 2 3,  Yu-Kun Guo # 4,  Shi-Bo Zhao 1 2 3,  Guo-Yu Yang 2 3 5,  Ying-Qian Han 6 7 8,  Bei-Bei Chu 9 10 11 12 13 14,  Sheng-Li Ming 15 16 17
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, Henan, China.
  • 2 Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, Henan, China.
  • 3 Key Laboratory of Animal Growth and Development of Henan Province, Henan Agricultural University, Zhengzhou, 450046, Henan, China.
  • 4 Animal Diseases and Public Health Engineering Research Center of Henan Province, College of Food and Drugs, Luoyang Polytechnic, Luoyang, 471023, Henan, China.
  • 5 International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou, 450046, Henan, China.
  • 6 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, Henan, China. twgjl@126.com.
  • 7 Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, Henan, China. twgjl@126.com.
  • 8 Key Laboratory of Animal Growth and Development of Henan Province, Henan Agricultural University, Zhengzhou, 450046, Henan, China. twgjl@126.com.
  • 9 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, Henan, China. chubeibei@henau.edu.cn.
  • 10 Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, Henan, China. chubeibei@henau.edu.cn.
  • 11 Key Laboratory of Animal Growth and Development of Henan Province, Henan Agricultural University, Zhengzhou, 450046, Henan, China. chubeibei@henau.edu.cn.
  • 12 Longhu Advanced Immunization Laboratory, Zhengzhou, 450046, Henan, China. chubeibei@henau.edu.cn.
  • 13 International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou, 450046, Henan, China. chubeibei@henau.edu.cn.
  • 14 Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou, 450046, Henan, China. chubeibei@henau.edu.cn.
  • 15 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, Henan, China. mingsl911102@163.com.
  • 16 Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, Henan, China. mingsl911102@163.com.
  • 17 Key Laboratory of Animal Growth and Development of Henan Province, Henan Agricultural University, Zhengzhou, 450046, Henan, China. mingsl911102@163.com.
  • # Contributed equally.
PMID: 38807225 DOI: 10.1186/s13567-024-01328-4
Abstract

Pseudorabies virus (PRV) is recognized as the aetiological agent responsible for Aujeszky's disease, or pseudorabies, in swine populations. Rab6, a member of the small GTPase family, is implicated in various membrane trafficking processes, particularly exocytosis regulation. Its involvement in PRV Infection, however, has not been documented previously. In our study, we observed a significant increase in the Rab6 mRNA and protein levels in both PK-15 porcine kidney epithelial cells and porcine alveolar macrophages, as well as in the lungs and spleens of mice infected with PRV. The overexpression of wild-type Rab6 and its GTP-bound mutant facilitated PRV proliferation, whereas the GDP-bound mutant form of Rab6 had no effect on viral propagation. These findings indicated that the GTPase activity of Rab6 was crucial for the successful spread of PRV. Further investigations revealed that the reduction in Rab6 levels through knockdown significantly hampered PRV proliferation and disrupted virus assembly and egress. At the molecular level, Rab6 was found to interact with the PRV glycoproteins gB and gE, both of which are essential for viral assembly and egress. Our results collectively suggest that PRV exploits Rab6 to expedite its assembly and egress and identify Rab6 as a promising novel target for therapeutic treatment for PRV Infection.

Keywords

PRV; Rab6; gB; gE; small GTPase; viral assembly and egress.

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