PT  - JOURNAL ARTICLE
AU  - Pei Xuan Lee
AU  - Donald Heng Rong Ting
AU  - Clement Peng Hee Boey
AU  - Eunice Tze Xin Tan
AU  - Janice Zuo Hui Chia
AU  - Li Ching Ong
AU  - Yen Leong Chua
AU  - Chanditha Hapuarachchi
AU  - Lee Ching Ng
AU  - Sylvie Alonso
TI  - Relative contribution of non-structural protein 1 in dengue pathogenesis
AID  - 10.1101/2020.02.01.929885
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.01.929885
4099  - http://biorxiv.org/content/early/2020/02/02/2020.02.01.929885.short
4100  - http://biorxiv.org/content/early/2020/02/02/2020.02.01.929885.full
AB  - 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.