Protective Efficacy of VP1-Specific Neutralizing Antibody Associated with a Reduction of Viral Load and Pro-Inflammatory Cytokines in Human SCARB2-Transgenic Mice

Hsuen Wen Chang, Yi Wen Lin, Hui Min Ho, Min Han Lin, Chia Chyi Liu, Hsiao Yun Shao, Pele Chong, Charles Sia, Yen Hung Chow

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Hand-foot-mouth diseases (HFMD) caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16) in children have now become a severe public health issue in the Asian-Pacific region. Recently we have successfully developed transgenic mice expressing human scavenger receptor class B member 2 (hSCARB2, a receptor of EV71 and CVA16) as an animal model for evaluating the pathogenesis of enterovirus infections. In this study, hSCARB2-transgenic mice were used to investigate the efficacy conferred by a previously described EV71 neutralizing antibody, N3. A single injection of N3 effectively inhibited the HFMD-like skin scurfs in mice pre-infected with clinical isolate of EV71 E59 (B4 genotype) or prevented severe limb paralysis and death in mice pre-inoculated with 5746 (C2 genotype). This protection was correlated with remarkable reduction of viral loads in the brain, spinal cord and limb muscles. Accumulated viral loads and the associated pro-inflammatory cytokines were all reduced. The protective efficacy of N3 was not observed in animals challenged with CVA16. This could be due to dissimilarity sequences of the neutralizing epitope found in CVA16. These results indicate N3 could be useful in treating severe EV71 infections and the hSCARB2-transgenic mouse could be used to evaluate the protective efficacy of potential anti-enterovirus agent candidates.

Original languageEnglish
Article numbere69858
JournalPLoS One
Volume8
Issue number7
DOIs
Publication statusPublished - Jul 30 2013
Externally publishedYes

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Enterovirus
viral load
Neutralizing Antibodies
Viral Load
neutralizing antibodies
Transgenic Mice
Class B Scavenger Receptors
Animals
cytokines
genetically modified organisms
Cytokines
mice
Public health
Hand, Foot and Mouth Disease
Enterovirus Infections
Muscle
Epitopes
Brain
Skin
hand, foot and mouth disease

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Protective Efficacy of VP1-Specific Neutralizing Antibody Associated with a Reduction of Viral Load and Pro-Inflammatory Cytokines in Human SCARB2-Transgenic Mice. / Chang, Hsuen Wen; Lin, Yi Wen; Ho, Hui Min; Lin, Min Han; Liu, Chia Chyi; Shao, Hsiao Yun; Chong, Pele; Sia, Charles; Chow, Yen Hung.

In: PLoS One, Vol. 8, No. 7, e69858, 30.07.2013.

Research output: Contribution to journalArticle

Chang, Hsuen Wen ; Lin, Yi Wen ; Ho, Hui Min ; Lin, Min Han ; Liu, Chia Chyi ; Shao, Hsiao Yun ; Chong, Pele ; Sia, Charles ; Chow, Yen Hung. / Protective Efficacy of VP1-Specific Neutralizing Antibody Associated with a Reduction of Viral Load and Pro-Inflammatory Cytokines in Human SCARB2-Transgenic Mice. In: PLoS One. 2013 ; Vol. 8, No. 7.
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