Human SCARB2 transgenic mice as an infectious animal model for enterovirus 71.

PLoS One. 2013;8(2):e57591.

Lin YW, Yu SL, Shao HY, Lin HY, Liu CC, Hsiao KN, Chitra E, Tsou YL, Chang HW, Sia C, Chong P, Chow YH.

Institute of Infectious Disease and Vaccinology, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.

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.

PMID: 23451246

 

Supplement:

A. 1x 107 pfu of EV71 E59 (B4)

Yen-Hung Chow-Picture1

B. 1x 107 pfu of EV71 N-2838 (B5)

Yen-Hung Chow-Picture b

C. 3x 105 pfu of 5746-tw98 (C2)

Yen-Hung Chow-Picture c

(A)  1-d-old hSCARB2-Tg mice were injected s.c. with 1×107 pfu of E59 (B4 genotype) or the N-2838 (B5 genotype) strain. HFMD-like hair loss associated with scurf (HLS) and neurological paralysis were observed. (C)  7-d-old hSCARB2-Tg mice were injected s.c. with 3×105 pfu of 5746-TW98 (C2 genotype) strain. Severe neurological paralysis were observed. Pictures were taken at day 6 after infection.

 

Multiselect Ultimate Query Plugin by InoPlugs Web Design Vienna | Webdesign Wien and Juwelier SchönmannMultiselect Ultimate Query Plugin by InoPlugs Web Design Vienna | Webdesign Wien and Juwelier Schönmann