Author(s): Nunes, Bruno Tardelli Diniz ; Fontes-Garfias, Camila R ; Shan, Chao ; Muruato, Antonio E ; Nunes, Jannyce G. C ; Burbano, Rommel M. R ; Vasconcelos, Pedro Fernando da Costa ; Shi, Pei-Yong ; Medeiros, Daniele Barbosa de Almeida
Date: 2020
Origin: Oasisbr
Subject(s): Zika virus / patogenicidade; Fatores de Virul?ncia; Linhagem Celular
This work was supported by Amon G. Carter Foundation; Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico: [Grant Number 303999/2016-0,440405/2016-5]; Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior: [Grant Number Zika fast track project]; John S. Dunn Foundation; Gilson Longenbaugh Foundation; NIH: [Grant Number AI127744,AI136126,AI142759];PAHO: [Grant Number SCON2016-01353]; Summerfield Robert Foundation; Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation; Sealy & Smith Foundation.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Department of Biochemistry & Molecular Biology. Galveston, TX, USA / Health Sciences Institute. Belem, PA, Brazil.
Department of Biochemistry & Molecular Biology. Galveston, TX, USA.
Department of Biochemistry & Molecular Biology. Galveston, TX, USA.
Department of Biochemistry & Molecular Biology. Galveston, TX, USA / Department of Microbiology & Immunology. Galveston, TX, USA.
Department of Biochemistry & Molecular Biology. Galveston, TX, USA / Health Sciences Institute. Belem, PA, Brazil.
Health Sciences Institute. Belem, PA, Brazil / Federal University of Par?. Biological Sciences Institute. Belem, PA, Brazil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Par? State University. Department of Pathology. Bel?m, PA, Brazil.
Department of Biochemistry & Molecular Biology. Galveston, TX, USA / Institute for Human Infections & Immunity. Galveston, TX, USA / Institute for Translational Science. Galveston, TX, USA / Sealy Institute of Vaccine Sciences. Galveston, TX, USA / Texas Medical Branch. Sealy Center for Structural Biology & Molecular Biophysics. Galveston, TX, USA.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Department of Biochemistry & Molecular Biology. Galveston, TX, USA / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Programa de P?s-Gradua??o em Virologia. Ananindeua, PA, Brasil / Health Sciences Institute. Bel?m, PA, Brazil.
The Asian lineage of Zika virus (ZIKV) is responsible for the recent epidemics in the Americas and severe disease, whereas the African lineage of ZIKV has not been reported to cause epidemics or severe disease. We constructed a cDNA infectious clone (IC) of an African ZIKV strain, which, together with our previously developed Asian ZIKV strain IC, allowed us to engineer chimeric viruses by swapping the structural and non-structural genes between the two lineages. Recombinant parental and chimeric viruses were analyzed in A129 and newborn CD1 mouse models. In the A129 mice, the African strain developed higher viremia, organ viral loading, and mortality rate. In CD1 mice, the African strain exhibited a higher neurovirulence than the Asian strain. A chimeric virus containing the structural genes from the African strain is more virulent than the Asian strain, whereas a chimeric virus containing the non-structural genes from the African strain exhibited a virulence comparable to the Asian strain. These results suggest that (i) African strain is more virulent than Asian strain and (ii) viral structural genes primarily determine the virulence difference between the two lineages in mouse models. Other factors may contribute to the discrepancy between the mouse and epidemic results.
