Lactoferrin blocks orthopoxvirus entry via heparan sulphate and regulates host antiviral pathways
Lili Tian, Hongbo Qin, Sha Li, Mengjie Zhang, Lu Zhuang, Bixia Hong, Ke Liu, Maochen Li, Siyue Li, Yaxin Wang, Lihua Song, Yang Liu, Yun Wang, Huiyu Liu, Yigang Tong, Huahao Fan
TL;DR
Lactoferrin is a promising antiviral treatment for orthopoxviruses that works by blocking virus entry and boosting the body's antiviral defenses.
Contribution
Lactoferrin's dual mechanism of blocking orthopoxvirus entry and modulating antiviral pathways is newly identified.
Findings
Lactoferrin blocks orthopoxvirus entry by binding to heparan sulphate proteoglycans.
Lactoferrin activates TGF-β-dependent antiviral pathways and enhances interferon production.
Lactoferrin reduces viral load and tissue damage in a murine model of vaccinia virus infection.
Abstract
Current antiviral therapies for orthopoxviruses face critical challenges, including limited efficacy and significant toxicity, which impede outbreak containment and clinical management. Here, we identify lactoferrin as a potent antiviral agent against multiple orthopoxvirus strains. Combination administration of lactoferrin with brincidofovir or tecovirimat demonstrated additive efficacy, suggesting a potential clinical strategy to reduce individual drug toxicity. Mechanistically, lactoferrin blocks viral entry by competitively binding to heparan sulphate proteoglycans (HSPGs). It also suppresses viral replication by regulating host antiviral pathways, including down-regulating cytokines and upregulating TGF-β-dependent antiviral signalling pathways. We identify TGFBI as a virus-responsive target regulated by lactoferrin. Lactoferrin treatment restores TGFBI expression and activates…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsInfant Nutrition and Health · Respiratory viral infections research · Autoimmune and Inflammatory Disorders Research