Mem Inst Oswaldo Cruz, Rio de Janeiro, 113(5) May 2018
Full paper

NS1 codon usage adaptation to humans in pandemic Zika virus

Caio César de Melo Freire1, Giuseppe Palmisano2, Carla T Braconi3,Fernanda R Cugola4, Fabiele B Russo4, Patricia CB Beltrão-Braga4,5, Atila Iamarino3,Daniel Ferreira de Lima Neto3, Amadou Alpha Sall6, Livia Rosa-Fernandes7,Martin R Larsen7, Paolo Marinho de Andrade Zanotto3/+

1Universidade Federal de São Carlos, Departamento de Genética e Evolução, São Carlos, SP, Brasil
2Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Parasitologia, São Paulo, SP, Brasil
3Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Microbiologia, Laboratório de Evolução Molecular e Bioinformática, São Paulo, SP, Brasil
4Universidade de São Paulo, Laboratório de Células-Tronco, Departamento de Cirurgia, São Paulo, SP, Brasil
5Universidade de São Paulo, Escola de Artes, Ciências e Humanidades, Departamento de Obstetrícia, São Paulo, SP, Brasil
6Institute Pasteur of Dakar, Dakar, Senegal7University of Southern Denmark, Department of Biochemistry and Molecular Biology, Odense, Denmark

DOI: 10.1590/0074-02760170385
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BACKGROUND Zika virus (ZIKV) was recognised as a zoonotic pathogen in Africa and southeastern Asia. Human infections were infrequently reported until 2007, when the first known epidemic occurred in Micronesia. After 2013, the Asian lineage of ZIKV spread along the Pacific Islands and Americas, causing severe outbreaks with millions of human infections. The recent human infections of ZIKV were also associated with severe complications, such as an increase in cases of Guillain-Barre syndrome and the emergence of congenital Zika syndrome.

OBJECTIVES Brinton 2013 4 To better understand the recent and rapid expansion of ZIKV, as well as the presentation of novel complications, we compared the genetic differences between the African sylvatic lineage and the Asian epidemic lineage that caused the recent massive outbreaks.

FINDINGS The epidemic lineages have significant codon adaptation in NS1 gene to translate these proteins in human and Aedes aegypti mosquito cells compared to the African zoonotic lineage. Accordingly, a Brazilian epidemic isolate (ZBR) produced more NS1 protein than the MR766 African lineage (ZAF) did, as indicated by proteomic data from infections of neuron progenitor cells-derived neurospheres. Although ZBR replicated more efficiently in these cells, the differences observed in the stoichiometry of ZIKV proteins were not exclusively explained by the differences in viral replication between Bahir et al. 2009 1 the lineages.

MAIN CONCLUSIONS Our findings suggest that natural, silent translational selection in the second half of 20th century could have improved the fitness of Asian ZIKV lineage in human and mosquito cells.


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Financial support: FAPESP (project #2014/17766-9), CNPq (project 421160/2016-0).
CCMF, AI, CTB and DFLN are supported by FAPESP (#2014/06090-4, #2012/04818-5, #2014/03911-7 and #2016/03605-9); GP is supported by FAPESP (grant #2014/06863); PMAZ held a CNPq scholarship.
+ Corresponding author:
Received 22 September 2017
Accepted 20 February 2018

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