Comparison of African, Asian, and American Zika Viruses in Swiss Webster mice: Virulence, neutralizing antibodies, and serotypes

Abstract

The sequence of Zika virus has evolved as it has spread out of Africa and into the Americas. It is unclear whether American strains of the virus define a new serotype. Here, we have tested the virulence and immunogenicity of three wild-type ZIKV strains in neonatal Swiss Webster mice. We found that all three ZIKV strains (African MR766, 1947; Asian FSS13025, 2010; and American, PRVABC59, 2015) are capable of killing neonatal mice after intracranial injection. Intraperitoneal injection with these viruses did not kill, but produced neutralizing antibodies as measured by a PRNT 50 assay. Sera from mice infected with each virus were tested for neutralizing activity against the infecting virus and also the other two viruses by a PRNT 50 assay. In general, the antibodies induced by each virus were good at neutralizing that virus (the homologous virus), but somewhat poorer at neutralizing the other two viruses (heterologous viruses). Antibodies induced by the African strain MR766 were about 4-fold worse at neutralizing the American strain PRVABC59 than the homologous strain, while antibodies induced by the American strain were about 10-fold worse at neutralizing the African strain than the homologous strain. Because the antibodies are cross-neutralizing at some level, the viruses do not form separate serotypes. Nevertheless, these results raise concern that the immunity conferred by the African virus may protect only relatively poorly against the new American strains. This has implications for the possible spread of the American ZIKV strains to Africa and Southeast Asia, and also for the development of vaccines.

High-throughput neutralization assay for multiple flaviviruses based on single-round infectious particles using dengue virus type 1 reporter replicon

“…In contrast, sera of mice immunized with pcZIKME Br (SHP2015; Asian strain) showed 4-fold higher titers against homologous ZIKA Br -SRIPs than against heterologous ZIKV Af -SRIPs. These data are consistent with previous reports of mice immunized with different strains of ZIKV 20 , 21 and suggested that a neutralization assay using multiple ZIKV strains for detection of serological differences between the ancestral African strain and Asian strain might be useful to determine precisely ZIKV infection. It will be of interest to explore these associations with various ZIKV strains.…”

The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis

“…Somewhat greater differences in cross-neutralization of African and American Zika virus strains were observed in recent work with postinfection sera of mice (115). Specifically, antibodies induced by the American strain (PRVABC59) (2015) neutralized the African strain (MR766) (1947) 10-fold less potently than the homologous American strain.…”

Evolution of Two Major Zika Virus Lineages: Implications for Pathology, Immune Response, and Vaccine Development

“…The A129 mouse is commonly used to study ZIKV because the virus has been shown to infect cells by targeting human STAT2 to suppress IFN signaling, and it has been proposed that since it does not bind murine STAT2, it cannot infect mice unless the type I IFN receptor is knocked out or blocked ( 1 ). Of additional note, the majority of investigations that utilize ZIKV grow their viral stocks in Vero cells, which do not produce IFN type I in response to a viral infection, and thus allows them to be permissive to ZIKV infections ( 103 , 104 ).…”