Human SCARB2 Transgenic Mice as an Infectious Animal Model for Enterovirus 71

Yi Wen Lin, Shu Ling Yu, Hsiao Yun Shao, Hsiang Yin Lin, Chia Chyi Liu, Kuang Nan Hsiao, Ebenezer Chitra, Yueh Liang Tsou, Hsuen Wen Chang, Charles Sia, Pele Chong, Yen Hung Chow

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62 Citations (Scopus)

Abstract

Enterovirus 71 (EV71) and coxsackievirus (CVA) are the most common causative factors for hand, foot, and mouth disease (HFMD) and neurological disorders in children. Lack of a reliable animal model is an issue in investigating EV71-induced disease manifestation in humans, and the current clinical therapies are symptomatic. We generated a novel EV71-infectious model with hSCARB2-transgenic mice expressing the discovered receptor human SCARB2 (hSCARB2). The challenge of hSCARB2-transgenic mice with clinical isolates of EV71 and CVA16 resulted in HFMD-like and neurological syndromes caused by E59 (B4) and N2838 (B5) strains, and lethal paralysis caused by 5746 (C2), N3340 (C4), and CVA16. EV71 viral loads were evident in the tissues and CNS accompanied the upregulated pro-inflammatory mediators (CXCL10, CCL3, TNF-α, and IL-6), correlating to recruitment of the infiltrated T lymphocytes that result in severe diseases. Transgenic mice pre-immunized with live E59 or the FI-E59 vaccine was able to resist the subsequent lethal challenge with EV71. These results indicate that hSCARB2-transgenic mice are a useful model for assessing anti-EV71 medications and for studying the pathogenesis induced by EV71.

Original languageEnglish
Article numbere57591
JournalPLoS One
Volume8
Issue number2
DOIs
Publication statusPublished - Feb 25 2013
Externally publishedYes

ASJC Scopus subject areas

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

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    Lin, Y. W., Yu, S. L., Shao, H. Y., Lin, H. Y., Liu, C. C., Hsiao, K. N., Chitra, E., Tsou, Y. L., Chang, H. W., Sia, C., Chong, P., & Chow, Y. H. (2013). Human SCARB2 Transgenic Mice as an Infectious Animal Model for Enterovirus 71. PLoS One, 8(2), [e57591]. https://doi.org/10.1371/journal.pone.0057591