Abstract
The Flavivirus genus contains many important human pathogens, including dengue, Japanese encephalitis (JE), tick-borne encephalitis (TBE), West Nile (WN), yellow fever (YF) and Zika (ZIK) viruses. While there are effective vaccines for a few flavivirus diseases (JE, TBE and YF), the majority do not have vaccines, including WN and ZIK. The flavivirus nonstructural 1 (NS1) protein has an unusual structure–function because it is glycosylated and forms different structures to facilitate different roles intracellularly and extracellularly, including roles in the replication complex, assisting in virus assembly, and complement antagonism. It also plays a role in protective immunity through antibody-mediated cellular cytotoxicity, and anti-NS1 antibodies elicit passive protection in animal models against a virus challenge. Historically, NS1 has been used as a diagnostic marker for the flavivirus infection due to its complement fixing properties and specificity. Its role in disease pathogenesis, and the strong humoral immune response resulting from infection, makes NS1 an excellent target for inclusion in candidate flavivirus vaccines.
Highlights
The Flavivirus genus contains many important human pathogens, including dengue (DEN), yellow fever (YF), Japanese encephalitis (JE), West Nile (WN), tick-borne encephalitis (TBE), and Zika viruses (ZIK) [1]
The studies involving nonstructural 1 (NS1) glycosylation knockouts highlight the importance of carbohydrates to correct the function of the protein and its relevance in the future generation of flavivirus vaccines
It is clear that generating a vaccine including NS1 for DENV presents a potential unique solution to the antibody-dependent enhancement dilemma associated with severe disease, which is related to antibodies against E protein epitopes
Summary
The Flavivirus genus contains many important human pathogens, including dengue (DEN), yellow fever (YF), Japanese encephalitis (JE), West Nile (WN), tick-borne encephalitis (TBE), and Zika viruses (ZIK) [1]. These viruses are commonly transmitted to vertebrate hosts via the bite of an infected mosquito or tick. A small percentage of individuals infected can progress to a severe disease state, including viscerotropic disease with YFV, neurotropic disease with encephalitic flaviviruses, and in the case of DEN, severe DEN, DEN hemorrhagic fever (DHF) or DEN shock syndrome (DSS) [2]. While there are effective vaccines for humans to control JE, Kyasanur Forest disease, TBE and YF viruses, and promising live attenuated vaccines for dengue, there is an urgent need to develop vaccines for other flaviviruses, including WN and Zika [3,4,5]
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