Zika structural genes determine the virulence of African and Asian lineages

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 wi...

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Veröffentlicht in:Emerging microbes & infections 2020-01, Vol.9 (1), p.1023-1033
Hauptverfasser: Nunes, Bruno T. D., Fontes-Garfias, Camila R., Shan, Chao, Muruato, Antonio E., Nunes, Jannyce G. C., Burbano, Rommel M. R., Vasconcelos, Pedro F. C., Shi, Pei-Yong, Medeiros, Daniele B. A.
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container_title Emerging microbes & infections
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creator Nunes, Bruno T. D.
Fontes-Garfias, Camila R.
Shan, Chao
Muruato, Antonio E.
Nunes, Jannyce G. C.
Burbano, Rommel M. R.
Vasconcelos, Pedro F. C.
Shi, Pei-Yong
Medeiros, Daniele B. A.
description 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.
doi_str_mv 10.1080/22221751.2020.1753583
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D. ; Fontes-Garfias, Camila R. ; Shan, Chao ; Muruato, Antonio E. ; Nunes, Jannyce G. C. ; Burbano, Rommel M. R. ; Vasconcelos, Pedro F. C. ; Shi, Pei-Yong ; Medeiros, Daniele B. A.</creator><creatorcontrib>Nunes, Bruno T. D. ; Fontes-Garfias, Camila R. ; Shan, Chao ; Muruato, Antonio E. ; Nunes, Jannyce G. C. ; Burbano, Rommel M. R. ; Vasconcelos, Pedro F. C. ; Shi, Pei-Yong ; Medeiros, Daniele B. A.</creatorcontrib><description>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. 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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. 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subjects Africa
African
Americas - epidemiology
Animals
Asia
Asian
Chlorocebus aethiops
Disease Models, Animal
Epidemics
Genes, Viral
Genetic Variation
Humans
Immunology
Infectious Diseases
Life Sciences & Biomedicine
lineages
Mice
Microbiology
Science & Technology
Vero Cells
Virulence
Virulence - genetics
Zika
Zika virus
Zika Virus - genetics
Zika Virus - isolation & purification
Zika Virus - pathogenicity
Zika Virus Infection - pathology
title Zika structural genes determine the virulence of African and Asian lineages
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