2. Academic Validation
  3. Retinol binding protein 4 enhances cellular cholesterol uptake to facilitate influenza A virus infection

Retinol binding protein 4 enhances cellular cholesterol uptake to facilitate influenza A virus infection

  • PLoS Pathog. 2025 Oct 27;21(10):e1013623. doi: 10.1371/journal.ppat.1013623.
Hejiao Zhao 1 2,  Yalu Zhang 1 2,  Qingbing Han 1 2,  Huanan Li 1 2,  Wenjun Liu 3 4 5,  Lei Sun 3 4 6,  Yingli Shang 1 2 7
Affiliations

Affiliations

  • 1 Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Taian, Shandong, China.
  • 2 Shandong Provincial Key Laboratory of Zoonoses, Shandong Agricultural University, Taian, Shandong, China.
  • 3 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • 4 Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
  • 5 Shenzhen Medical Academy of Research and Translation (SMART), Shenzhen, Guangdong, China.
  • 6 Shandong Public Health Clinical Center, Jinan, Shandong, China.
  • 7 Institute of Immunology, Shandong Agricultural University, Taian, Shandong, China.
PMID: 41144502 DOI: 10.1371/journal.ppat.1013623
Abstract

Viruses hijack host cell machinery to facilitate their own replication. Therefore, identifying key cellular factors and processes involved in viral Infection is crucial for developing host-directed therapies. Herein, we demonstrate that retinol-binding protein 4 (RBP4), a Lipocalin Family member and major retinol carrier, is significantly induced by influenza A virus (IAV) Infection in both cellular models and clinical patients. Moreover, RBP4 deficiency impairs IAV replication both in vitro and in vivo. Mechanistically, RBP4 promotes the expression of CD36, a Cholesterol uptake receptor protein, thereby increasing cellular Cholesterol levels. This elevation in Cholesterol subsequently boosts cell-surface sialic acid levels, facilitating IAV attachment. Consequently, enforced expression of CD36 restores IAV replication in RBP4-deficient cells and mice. In summary, our study identifies RBP4 as a pivotal host factor that facilitates IAV Infection by modulating cellular Cholesterol homeostasis.

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