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bioRxiv · 10.1101/2020.02.01.929885

Relative contribution of non-structural protein 1 in dengue pathogenesis

LEE, P.·TING, D. H. R.·Boey, C. P. H.·TAN, E. T. X.·Chia, J. Z. H.·ONG, L. C.·CHUA, Y. L.·Hapuarachchi, C.·NG, L. C.·ALONSO, S.
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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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LEE, P., TING, D. H. R., Boey, C. P. H., TAN, E. T. X., Chia, J. Z. H., ONG, L. C., CHUA, Y. L., Hapuarachchi, C., NG, L. C., ALONSO, S.. 2020-02-02. Relative contribution of non-structural protein 1 in dengue pathogenesis. https://doi.org/10.1101/2020.02.01.929885

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