Zika structural genes determine the virulence of African and Asian lineages

ABSTRACT

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.

KEYWORDS:

• Zika
• virulence
• lineages
• African
• Asian

Acknowledgments

P.-Y.S. was supported by a grant from Pan American Health Organization SCON2016-01353, NIH grants AI142759, AI127744, and AI136126, and awards from the Kleberg Foundation, John S. Dunn Foundation, Amon G. Carter Foundation, Gilson Longenbaugh Foundation, and Summerfield Robert Foundation. P.F.C.V. was supported by the Ministry of Health of Brazil and by the grants from CNPq (process 303999/2016-0 and 440405/2016-5) and CAPES (Zika fast track project). We thank Scott Weaver at the Department of Microbiology and Immunology/UTMB for providing the animal models for the study as well as the Animal Resource Center and Sasha Azar for their assistance in maintaining the A129 mouse breeding colony.

Disclosure statement

The authors certify that they have NO affiliations with or involvement in any organization or entity with neither financial or non-financial interest in the subject matter or materials discussed in this manuscript.

Additional information

Funding

This work was supported by Amon G. Carter Foundation; Conselho Nacional de Desenvolvimento Científico e Tecnológico: [Grant Number 303999/2016-0,440405/2016-5]; Coordenação de Aperfeiçoamento de Pessoal de Nível 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.