title: L-ficolin binds to the glycoproteins hemagglutinin and neuraminidase and inhibits influenza A virus infection both in vitro and in vivo.
abstract: L-ficolin, one of the complement lectins found in human serum, is a novel pattern recognition molecule that can specifically bind to microbial carbohydrates, thereby activating the lectin complement pathway and mounting a protective innate immune response. However, little is known about the role of L-ficolin during viral infections in vivo. In the present study, we used a mouse model of influenza A virus infection to demonstrate that the administration of exogenous L-ficolin or ficolin A (FCNA - an L-ficolin-like molecule in the mouse) is protective against the virus. Furthermore, FCNA-null mice have a greatly increased susceptibility to infection with the influenza A virus. Moreover, we found recombinant human L-ficolin inhibited influenza A virus entry into Madin-Darby canine kidney cells. More importantly, L-ficolin can recognize and bind hemagglutinin (HA) and neuraminidase (NA) glycoproteins and different subtypes of influenza A virus, and these interactions can be competitively inhibited by N-acetyl-D-glucosamine. In addition, the binding of L-ficolin and FCNA may lead to the activation of the lectin complement pathway. To our knowledge, this is the first report demonstrating that L-ficolin can block influenza virus infections both in vitro and in vivo using FCNA-knockout mice, possibly by interacting with the carbohydrates of HA and NA. Therefore, these data may provide new immunotherapeutic strategies based on the innate immune molecule L-ficolin against the influenza A virus.
authors.affiliation: State Key Laboratory of Virology, Department of Immunology and Hubei Province, Key Laboratory of Allergy and Immune-Related Diseases, Wuhan University School of Medicine, Wuhan, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.forename: Haidan
authors.initials: H
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Victor Tunje
authors.initials: VT
authors.lastname: Jeza
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.forename: Yinglan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Tian
authors.initials: T
authors.lastname: Xiang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yuchi
authors.initials: Y
authors.lastname: Endo
authors.forename: Teizo
authors.initials: T
authors.lastname: Fujita
authors.forename: Xiao-Lian
authors.initials: XL
authors.lastname: Zhang
mesh_terms: D000117:Acetylglucosamine / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D037582:Complement Pathway, Mannose-Binding Lectin / Q000235:genetics; D004195:Disease Models, Animal; D006388:Hemagglutinins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity / Q000502:physiology*; D037102:Lectins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D053586:Virus Internalization; D000097604:Ficolins
chemical_list: D000117:Acetylglucosamine; D006388:Hemagglutinins; D037102:Lectins; D009439:Neuraminidase; D000097604:Ficolins