Asian lineage of Zika virus RNA pseudoknot may induce ribosomal frameshift and produce a new neuroinvasive protein ZIKV-NS1’

Tambonis, T.; Contessoto, V.; Bittar, C.; Calmon, M. F.; Nogueira, M. L.; Rahal, P.; Leite, V. B. P.

doi:10.1101/105809

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bioRxiv · 10.1101/105809

Asian lineage of Zika virus RNA pseudoknot may induce ribosomal frameshift and produce a new neuroinvasive protein ZIKV-NS1’

Tambonis, T.·Contessoto, V.·Bittar, C.·Calmon, M. F.·Nogueira, M. L.·Rahal, P.·Leite, V. B. P.

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Abstract

Zika virus (ZIKV) is a threat to humanity, and understanding its neuroinvasiveness is a major challenge. Microcephaly observed in neonates in Brazil is associated with ZIKV that belongs to the Asian lineage. What distinguishes the neuroinvasiveness between the RNA lineages from Asia and Africa is still unknown. Here we identify an aspect that may explain the different behavior between the two lineages. The distinction between the two groups is the occurrence of an alternative protein NS1 (ZIKV-NS1), which happens through a pseudoknot in the virus RNA that induces a ribosomal frameshift. Presence of NS1 protein is also observed in other Flavivirus that are neuroinvasive, and when NS1 production issuppressed, neuroinvasiveness is reduced.1 This evidence gives grounds to suggest that the ZIKV-NS1 occurring in the Asian lineage is responsible for neuro-tropism, which causes the neuro-pathologies associated with ZIKV infection, of which microcephaly is the most dev astating. The existence of ZIKV-NS1, which only exists in the Asian lineage, was inferred through bioinformatic methods, and it has yet to be experimentally observed. If its occurrence is confirmed, it will be a potential target in fighting the neuro-diseases associated with ZIKV.

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Tambonis, T., Contessoto, V., Bittar, C., Calmon, M. F., Nogueira, M. L., Rahal, P., Leite, V. B. P.. 2017-02-03. Asian lineage of Zika virus RNA pseudoknot may induce ribosomal frameshift and produce a new neuroinvasive protein ZIKV-NS1’. https://doi.org/10.1101/105809

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