Mutations present in a low-passage Zika virus isolate result in attenuated pathogenesis in mice
| Autor: | Hannah Romo, Gregory D. Ebel, Jana M. Ritter, Erin M. McDonald, Seth A. Hawks, James Weger-Lucarelli, Nisha K. Duggal, Aaron C. Brault |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Sexual transmission Viral pathogenesis Clone (cell biology) Genitalia Male Article Virus Zika virus Mouse model Mice 03 medical and health sciences Virology Chlorocebus aethiops Animals Humans Vero Cells 030304 developmental biology 0303 health sciences biology Zika Virus Infection Flavivirus 030302 biochemistry & molecular biology Zika Virus Vaccine efficacy biology.organism_classification Spermatozoa Disease Models Animal Mutation Vero cell |
| Zdroj: | Virology. 530:19-26 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2019.02.004 |
| Popis: | Zika virus (ZIKV) infection can result in neurological disorders including Congenital Zika Syndrome in infants exposed to the virus in utero. Pregnant women can be infected by mosquito bite as well as by sexual transmission from infected men. Herein, the variants of ZIKV within the male reproductive tract and ejaculates were assessed in inoculated mice. We identified two non-synonymous variants at positions E-V330L and NS1-W98G. These variants were also present in the passage three PRVABC59 isolate and infectious clone relative to the patient serum PRVABC59 sequence. In subsequent studies, ZIKV E-330L was less pathogenic in mice than ZIKV E-330V as evident by increased average survival times. In Vero cells, ZIKV E-330L/NS1-98G outcompeted ZIKV E-330V/NS1-98W within 3 passages. These results suggest that the E-330L/NS1-98G variants are attenuating in mice and were enriched during cell culture passaging. Cell culture propagation of ZIKV could significantly affect animal model development and vaccine efficacy studies. NIH [AI067380] This work was supported in part by NIH grant AI067380 (G.D.E.). We thank DVBD staff members Jason Velez for cell culture support and Sean Masters for his excellent contributions to animal husbandry and animal care needs throughout this study. The findings and conclusions of this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the U.S. Agency for International Development. |
| Databáze: | OpenAIRE |
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