tetano
Editor, Senior Moderator
PLoS Pathog
. 2025 Oct 27;21(10):e1013623.
doi: 10.1371/journal.ppat.1013623. eCollection 2025 Oct. Retinol binding protein 4 enhances cellular cholesterol uptake to facilitate influenza A virus infection
Hejiao Zhao[SUP] 1 2 [/SUP], Yalu Zhang[SUP] 1 2 [/SUP], Qingbing Han[SUP] 1 2 [/SUP], Huanan Li[SUP] 1 2 [/SUP], Wenjun Liu[SUP] 3 4 5 [/SUP], Lei Sun[SUP] 3 4 6 [/SUP], Yingli Shang[SUP] 1 2 7 [/SUP]
Affiliations
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.
. 2025 Oct 27;21(10):e1013623.
doi: 10.1371/journal.ppat.1013623. eCollection 2025 Oct. Retinol binding protein 4 enhances cellular cholesterol uptake to facilitate influenza A virus infection
Hejiao Zhao[SUP] 1 2 [/SUP], Yalu Zhang[SUP] 1 2 [/SUP], Qingbing Han[SUP] 1 2 [/SUP], Huanan Li[SUP] 1 2 [/SUP], Wenjun Liu[SUP] 3 4 5 [/SUP], Lei Sun[SUP] 3 4 6 [/SUP], Yingli Shang[SUP] 1 2 7 [/SUP]
Affiliations
- PMID: 41144502
- PMCID: PMC12558542
- DOI: 10.1371/journal.ppat.1013623
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.