Next Article in Journal
Sea Bass Immunization to Downsize the Betanodavirus Protein Displayed in the Surface of Inactivated Repair-Less Bacteria
Previous Article in Journal
The Increase of the Magnitude of Spontaneous Viral Blips in Some Participants of Phase II Clinical Trial of Therapeutic Optimized HIV DNA Vaccine Candidate
Open AccessArticle

Attenuation of Zika Virus by Passage in Human HeLa Cells

1
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
2
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
3
Viral Disease Branch, Walter Reed Army Institute for Research, Silver Spring, MD 20910, USA
4
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA
5
Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA
6
Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA
7
Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA
*
Author to whom correspondence should be addressed.
Vaccines 2019, 7(3), 93; https://doi.org/10.3390/vaccines7030093
Received: 27 June 2019 / Revised: 14 August 2019 / Accepted: 16 August 2019 / Published: 20 August 2019
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. View Full-Text
Keywords: Zika virus; attenuation; flavivirus; HeLa cells; Zika virus prM; Zika virus NS1 Zika virus; attenuation; flavivirus; HeLa cells; Zika virus prM; Zika virus NS1
Show Figures

Graphical abstract

MDPI and ACS Style

Li, L.; Collins, N.D.; Widen, S.G.; Davis, E.H.; Kaiser, J.A.; White, M.M.; Greenberg, M.B.; Barrett, A.D.T.; Bourne, N.; Sarathy, V.V. Attenuation of Zika Virus by Passage in Human HeLa Cells. Vaccines 2019, 7, 93.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop