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Relative contribution of non-structural protein 1 in dengue pathogenesis

PeiXuan LEE, Donald Heng Rong TING, Clement Peng Hee Boey, Eunice Tze Xin TAN, Janice Zuo Hui Chia, Li Ching ONG, Yen Leong CHUA, Chanditha Hapuarachchi, Lee Ching NG, SYLVIE ALONSO
doi: https://doi.org/10.1101/2020.02.01.929885
PeiXuan LEE
National University of Singapore;
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  • For correspondence: leepeixuan1@gmail.com
Donald Heng Rong TING
National University of Singapore;
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  • For correspondence: micdthr@nus.edu.sg
Clement Peng Hee Boey
National University of Singapore;
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  • For correspondence: e0431456@u.nus.edu
Eunice Tze Xin TAN
National University of Singapore;
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  • For correspondence: e0002278@u.nus.edu
Janice Zuo Hui Chia
National University of Singapore;
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  • For correspondence: sasylvie1@gmail.com
Li Ching ONG
National University of Singapore;
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  • For correspondence: ong_liching@hotmail.com
Yen Leong CHUA
National University of Singapore;
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  • For correspondence: miccyl@nus.edu.sg
Chanditha Hapuarachchi
Environmental Health Institute;
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  • For correspondence: chanditha_hapuarachchi@nea.gov.sg
Lee Ching NG
Environmental Health Institute;
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  • For correspondence: ng_lee_ching@nea.gov.sg
SYLVIE ALONSO
NATIONAL UNIVERSITY OF SINGAPORE
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  • For correspondence: micas@nus.edu.sg
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Abstract

Dengue is a major public health concern in the tropical and sub-tropical world with no effective treatment. The controversial live attenuated virus vaccine Dengvaxia has boosted the pursuit of sub-unit vaccine approaches, and the non-structural protein 1 (NS1) has recently emerged as a promising candidate. However, we found that NS1 immunization or passive transfer of NS1 antibodies failed to confer protection in symptomatic dengue mouse models using two non mouse-adapted DENV2 strains from the Cosmopolitan genotype that currently circulates in South-East Asia. Furthermore, exogenous administration of purified NS1 did not worsen in vivo vascular leakage in sub-lethally infected mice, thereby supporting that NS1 does not play a critical role in the pathogenesis of these DENV2 strains. Virus chimerization approaches indicated that the prME structural region, but not NS1, plays a critical role in driving in vivo fitness and virulence of the virus, through induction of key pro-inflammatory cytokines. This work highlights that the pathogenic role of NS1 is DENV strain-dependent, which warrants re-evaluation of NS1 as a universal dengue vaccine candidate.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted February 02, 2020.
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Relative contribution of non-structural protein 1 in dengue pathogenesis
PeiXuan LEE, Donald Heng Rong TING, Clement Peng Hee Boey, Eunice Tze Xin TAN, Janice Zuo Hui Chia, Li Ching ONG, Yen Leong CHUA, Chanditha Hapuarachchi, Lee Ching NG, SYLVIE ALONSO
bioRxiv 2020.02.01.929885; doi: https://doi.org/10.1101/2020.02.01.929885
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Relative contribution of non-structural protein 1 in dengue pathogenesis
PeiXuan LEE, Donald Heng Rong TING, Clement Peng Hee Boey, Eunice Tze Xin TAN, Janice Zuo Hui Chia, Li Ching ONG, Yen Leong CHUA, Chanditha Hapuarachchi, Lee Ching NG, SYLVIE ALONSO
bioRxiv 2020.02.01.929885; doi: https://doi.org/10.1101/2020.02.01.929885

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