2. Academic Validation
  3. Role of Rab35 in modulating lipid metabolism and viral entry during pseudorabies virus infection

Role of Rab35 in modulating lipid metabolism and viral entry during pseudorabies virus infection

  • Int J Biol Macromol. 2024 Dec;282(Pt 6):137492. doi: 10.1016/j.ijbiomac.2024.137492.
Meng-Pan Cai 1,  Cheng-Long Qu 1,  Meng-Hua Du 1,  Shu-Yi Wang 1,  Guo-Yu Yang 2,  Bei-Bei Chu 3,  Sheng-Li Ming 4
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou 450046, Henan Province, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou 450046, Henan Province, China.
  • 2 Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou 450046, Henan Province, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou 450046, Henan Province, China.
  • 3 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou 450046, Henan Province, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou 450046, Henan Province, China; Longhu Advanced Immunization Laboratory, Zhengzhou 450046, Henan Province, China; International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou 450046, Henan Province, China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450046, Henan Province, China. Electronic address: chubeibei@henau.edu.cn.
  • 4 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou 450046, Henan Province, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou 450046, Henan Province, China. Electronic address: mingsl911102@163.com.
PMID: 39528177 DOI: 10.1016/j.ijbiomac.2024.137492
Abstract

Pseudorabies virus (PRV), the causative agent of Aujeszky's disease in swine, is a significant pathogen in veterinary medicine. Rab35 is a key regulatory GTPase involved in diverse cellular functions, including endocytic recycling, cytokinesis, and the regulation of the actin Cytoskeleton. Although Rab35's roles in these processes are well-documented, its contribution to PRV replication dynamics had not been previously elucidated. Our study demonstrated that PRV Infection led to an increase in Rab35 expression at both the mRNA and protein levels in both in vitro Cell Culture and in vivo models. Elevated Rab35 expression was associated with an acceleration of PRV replication, whereas knocking down Rab35 expression significantly impeded viral proliferation. Further investigation revealed that while Rab35 depletion did not impact the initial attachment of PRV to host cells, it critically suppressed subsequent viral entry and effectively obstructed the transcription of early PRV genes. The downregulation of Rab35 disrupted the expression of Enzymes critical to lipid synthesis, which are upregulated during PRV Infection. Moreover, Rab35 knockdown disrupted lipid dynamics necessary for the virus to integrate into clathrin-coated pits, a pivotal mechanism for PRV cellular entry. These findings collectively suggest that Rab35 plays a facilitatory role in PRV Infection by modulating lipid metabolism and the viral entry process, thereby offering new insights into the complex intracellular mechanisms underlying PRV replication.

Keywords

Clathrin-coated pits; Lipid metabolism; PRV; Rab35; Viral entry.

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