Differential Neurovirulence of African and Asian Genotype Zika Virus Isolates in Outbred Immunocompetent Mice
Open accessAbstract
Although first isolated almost 70 years ago, Zika virus (ZIKV; Flavivirus, Flaviviridae) has only recently been associated with significant outbreaks of disease in humans. Several severe ZIKV disease manifestations have also been recently documented, including fetal malformations, such as microcephaly, and Guillain–Barré syndrome in adults. Although principally transmitted by mosquitoes, sexual transmission of ZIKV has been documented. Recent publications of several interferon receptor knockout mouse models have demonstrated ZIKV-induced disease. Herein, outbred immunocompetent CD-1/ICR adult mice were assessed for susceptibility to disease by intracranial (i.c.) and intraperitoneal (i.p.) inoculation with the Ugandan prototype strain (MR766; African genotype), a low-passage Senegalese strain (DakAr41524; African genotype) and a recent ZIKV strain isolated from a traveler infected in Puerto Rico (PRVABC59; Asian genotype). Morbidity was not observed in mice inoculated by the i.p. route with either MR766 or PRVABC59 for doses up to 6 log10 PFU. In contrast, CD-1/ICR mice inoculated i.c. with the MR766 ZIKV strain exhibited an 80–100% mortality rate that was age independent. The DakAr41524 strain delivered by the i.c route caused 30% mortality, and the Puerto Rican ZIKV strain failed to elicit mortality but did induce a serum neutralizing immune response in 60% of mice. These data provide a potential animal model for assessing neurovirulence determinants of different ZIKV strains as well as a potential immunocompetent challenge model for assessing protective efficacy of vaccine candidates.
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- Authors
- Duggal, N. K., Ritter, J. M., McDonald, E. M., Romo, H., Guirakhoo, F., Davis, B. S., Chang, G.-J. J., & Brault, A. C.
- Affiliations
- Centers for Disease Control and Prevention (US)
- GeoVax (United States) (US)
- Corresponding author
- Brault, Aaron C.
- ORCID
- Venue
- The American Journal of Tropical Medicine and Hygiene
- Published
- 2017-11-08
- Volume
- 97
- Issue
- 5
- Pages
- 1410-1417
- ISSN
- 0002-9637 (ISSN-L)
- 1476-1645
- PMC
- PMC5817768
- OpenAlex
- W2749582671
- Cited by
- 52
- References
- 30
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 10 · 2020: 5 · 2019: 9 · 2018: 12 · 2017: 3
- FWCI
- 7.43
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- other-oa
- Locations
- American Journal of Tropical Medicine and Hygiene (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
- Keywords
- Zika virus, neurovirulence, Asian genotype, intracranial inoculation, intraperitoneal inoculation, mouse model, immunocompetent mice, disease susceptibility, neutralizing antibodies, vaccine efficacy evaluation, flavivirus
- MeSH terms
- Zika Virus Infection, Zika Virus, Animals, Chlorocebus aethiops, Disease Models, Animal, Female, Genotype, Humans, Mice, Inbred ICR, Neurons, Vero Cells, Virulence, Virus Replication, Cell Line, Tumor, Mice
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