Bovine Lactoferrin Inhibits Dengue Virus Infectivity by Interacting with Heparan Sulfate, Low-Density Lipoprotein Receptor, and DC-SIGN

Bovine lactoferrin (bLF) presents in milk and has been shown to inhibit several viral infections. Effective drugs are unavailable for the treatment of dengue virus (DENV) infection. In this study, we evaluated the antiviral effect of bLF against DENV infection in vivo and in vitro. Bovine LF signifi...

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Published inInternational journal of molecular sciences Vol. 18; no. 9; p. 1957
Main Authors Chen, Jo-Mei, Fan, Yi-Chin, Lin, Jen-Wei, Chen, Yi-Ying, Hsu, Wei-Li, Chiou, Shyan-Song
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 12.09.2017
MDPI
Subjects
Animals
Antiviral Agents - pharmacology
Cattle
Cell Adhesion Molecules - metabolism
Cell Line
Cercopithecus aethiops
Dengue - drug therapy
Dengue fever
Dengue Virus - drug effects
Female
Heparan sulfate
Heparitin Sulfate - metabolism
Humans
Infections
Inhibitory Concentration 50
Lactoferrin - pharmacology
Lectins, C-Type - metabolism
Low density lipoprotein
Mice
Mice, Inbred BALB C
Pregnancy
Receptors, Cell Surface - metabolism
Receptors, LDL - metabolism
Receptors, Virus - drug effects
THP-1 Cells
Vero Cells
Viral infections
Viral Plaque Assay
Virus Attachment - drug effects
heparan sulfate
low-density lipoprotein receptor
DC-SIGN
bovine lactoferrin
dengue virus
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Abstract Bovine lactoferrin (bLF) presents in milk and has been shown to inhibit several viral infections. Effective drugs are unavailable for the treatment of dengue virus (DENV) infection. In this study, we evaluated the antiviral effect of bLF against DENV infection in vivo and in vitro. Bovine LF significantly inhibited the infection of the four serotypes of DENV in Vero cells. In the time-of-drug addition test, DENV-2 infection was remarkably inhibited when bLF was added during or prior to the occurrence of virus attachment. We also revealed that bovine LF blocks binding between DENV-2 and the cellular membrane by interacting with heparan sulfate (HS), dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), and low-density lipoprotein receptors (LDLR). In addition, bLF inhibits DENV-2 infection and decreases morbidity in a suckling mouse challenge model. This study supports the finding that bLF may inhibit DENV infection by binding to the potential DENV receptors.
AbstractList Bovine lactoferrin (bLF) presents in milk and has been shown to inhibit several viral infections. Effective drugs are unavailable for the treatment of dengue virus (DENV) infection. In this study, we evaluated the antiviral effect of bLF against DENV infection in vivo and in vitro. Bovine LF significantly inhibited the infection of the four serotypes of DENV in Vero cells. In the time-of-drug addition test, DENV-2 infection was remarkably inhibited when bLF was added during or prior to the occurrence of virus attachment. We also revealed that bovine LF blocks binding between DENV-2 and the cellular membrane by interacting with heparan sulfate (HS), dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), and low-density lipoprotein receptors (LDLR). In addition, bLF inhibits DENV-2 infection and decreases morbidity in a suckling mouse challenge model. This study supports the finding that bLF may inhibit DENV infection by binding to the potential DENV receptors.Bovine lactoferrin (bLF) presents in milk and has been shown to inhibit several viral infections. Effective drugs are unavailable for the treatment of dengue virus (DENV) infection. In this study, we evaluated the antiviral effect of bLF against DENV infection in vivo and in vitro. Bovine LF significantly inhibited the infection of the four serotypes of DENV in Vero cells. In the time-of-drug addition test, DENV-2 infection was remarkably inhibited when bLF was added during or prior to the occurrence of virus attachment. We also revealed that bovine LF blocks binding between DENV-2 and the cellular membrane by interacting with heparan sulfate (HS), dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), and low-density lipoprotein receptors (LDLR). In addition, bLF inhibits DENV-2 infection and decreases morbidity in a suckling mouse challenge model. This study supports the finding that bLF may inhibit DENV infection by binding to the potential DENV receptors.
Bovine lactoferrin (bLF) presents in milk and has been shown to inhibit several viral infections. Effective drugs are unavailable for the treatment of dengue virus (DENV) infection. In this study, we evaluated the antiviral effect of bLF against DENV infection in vivo and in vitro. Bovine LF significantly inhibited the infection of the four serotypes of DENV in Vero cells. In the time-of-drug addition test, DENV-2 infection was remarkably inhibited when bLF was added during or prior to the occurrence of virus attachment. We also revealed that bovine LF blocks binding between DENV-2 and the cellular membrane by interacting with heparan sulfate (HS), dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), and low-density lipoprotein receptors (LDLR). In addition, bLF inhibits DENV-2 infection and decreases morbidity in a suckling mouse challenge model. This study supports the finding that bLF may inhibit DENV infection by binding to the potential DENV receptors.
Author Chen, Jo-Mei
Lin, Jen-Wei
Chiou, Shyan-Song
Hsu, Wei-Li
Fan, Yi-Chin
Chen, Yi-Ying
AuthorAffiliation Graduate Institute of Microbiology and Public Health, College of Veterinary Medicine, National Chung Hsing University, Taichung 40227, Taiwan; chenjm0317@gmail.com (J.-M.C.); yichinfan0309@gmail.com (Y.-C.F.); provista.wei@gmail.com (J.-W.L.); irisgf1986@gmail.com (Y.-Y.C.); wlhsu@dragon.nchu.edu.tw (W.-L.H.)
AuthorAffiliation_xml – name: Graduate Institute of Microbiology and Public Health, College of Veterinary Medicine, National Chung Hsing University, Taichung 40227, Taiwan; chenjm0317@gmail.com (J.-M.C.); yichinfan0309@gmail.com (Y.-C.F.); provista.wei@gmail.com (J.-W.L.); irisgf1986@gmail.com (Y.-Y.C.); wlhsu@dragon.nchu.edu.tw (W.-L.H.)
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Keywords heparan sulfate
low-density lipoprotein receptor
DC-SIGN
bovine lactoferrin
dengue virus
Language English
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Snippet Bovine lactoferrin (bLF) presents in milk and has been shown to inhibit several viral infections. Effective drugs are unavailable for the treatment of dengue...
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pubmed
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StartPage 1957
SubjectTerms Animals
Antiviral Agents - pharmacology
Cattle
Cell Adhesion Molecules - metabolism
Cell Line
Cercopithecus aethiops
Dengue - drug therapy
Dengue fever
Dengue Virus - drug effects
Female
Heparan sulfate
Heparitin Sulfate - metabolism
Humans
Infections
Inhibitory Concentration 50
Lactoferrin - pharmacology
Lectins, C-Type - metabolism
Low density lipoprotein
Mice
Mice, Inbred BALB C
Pregnancy
Receptors, Cell Surface - metabolism
Receptors, LDL - metabolism
Receptors, Virus - drug effects
THP-1 Cells
Vero Cells
Viral infections
Viral Plaque Assay
Virus Attachment - drug effects
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Title Bovine Lactoferrin Inhibits Dengue Virus Infectivity by Interacting with Heparan Sulfate, Low-Density Lipoprotein Receptor, and DC-SIGN
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Volume 18
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