Attenuation of Zika Virus by Passage in Human HeLa Cells
| Autor: | Natalie D. Collins, Li Li, Jaclyn A. Kaiser, Steven G. Widen, M. Banks Greenberg, Vanessa V. Sarathy, Alan D.T. Barrett, Emily H. Davis, Mellodee White, Nigel Bourne |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
viruses 030231 tropical medicine Immunology lcsh:Medicine Viremia Article Virus Zika virus HeLa 03 medical and health sciences 0302 clinical medicine flavivirus Drug Discovery parasitic diseases medicine Pharmacology (medical) HeLa cells attenuation Plaque-forming unit Pharmacology Zika virus prM Zika virus NS1 biology Yellow fever lcsh:R virus diseases Japanese encephalitis biochemical phenomena metabolism and nutrition medicine.disease biology.organism_classification Virology Flavivirus 030104 developmental biology Infectious Diseases |
| Zdroj: | Vaccines, Vol 7, Iss 3, p 93 (2019) Vaccines Volume 7 Issue 3 |
| Popis: | Zika virus (ZIKV) is a mosquito-borne Flavivirus. Previous studies have shown that mosquito-transmitted flaviviruses, including yellow fever, Japanese encephalitis, and West Nile viruses, could be attenuated by serial passaging in human HeLa cells. Therefore, it was hypothesized that wild-type ZIKV would also be attenuated after HeLa cell passaging. A human isolate from the recent ZIKV epidemic was subjected to serial HeLa cell passaging, resulting in attenuated in vitro replication in both Vero and A549 cells. Additionally, infection of AG129 mice with 10 plaque forming units (pfu) of wild-type ZIKV led to viremia and mortality at 12 days, whereas infection with 103 pfu of HeLa-passage 6 (P6) ZIKV led to lower viremia, significant delay in mortality (median survival: 23 days), and increased cytokine and chemokine responses. Genomic sequencing of HeLa-passaged virus identified two amino acid substitutions as early as HeLa-P3: pre-membrane E87K and nonstructural protein 1 R103K. Furthermore, both substitutions were present in virus harvested from HeLa-P6-infected animal tissue. Together, these data show that, similarly to other mosquito-borne flaviviruses, ZIKV is attenuated following passaging in HeLa cells. This strategy can be used to improve understanding of substitutions that contribute to attenuation of ZIKV and be applied to vaccine development across multiple platforms. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|