A Small-Plaque Isolate of the Zika Virus with Envelope Domain III Mutations Affect Viral Entry and Replication in Mammalian but Not Mosquito Cells
Issued Date
2022-03-01
Resource Type
eISSN
19994915
Scopus ID
2-s2.0-85125620965
Pubmed ID
35336887
Journal Title
Viruses
Volume
14
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
Viruses Vol.14 No.3 (2022)
Suggested Citation
Jaimipuk T., Sachdev S., Yoksan S., Thepparit C. A Small-Plaque Isolate of the Zika Virus with Envelope Domain III Mutations Affect Viral Entry and Replication in Mammalian but Not Mosquito Cells. Viruses Vol.14 No.3 (2022). doi:10.3390/v14030480 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85014
Title
A Small-Plaque Isolate of the Zika Virus with Envelope Domain III Mutations Affect Viral Entry and Replication in Mammalian but Not Mosquito Cells
Author(s)
Author's Affiliation
Other Contributor(s)
Abstract
An Asian Zika virus (ZIKV) isolated from a Thai patient that was serially passaged in Primary Dog Kidney (PDK) cells for attenuation displayed both big and small plaque-forming viruses by the 7th passage. Two small-plaque isolates were selected and purified for characterization as attenuated ZIKV candidates. In vitro growth kinetics showed significantly reduced titers for smallplaque isolates in Vero cells early post-infection compared to the parental ZIKV and a big-plaque isolate, but no significant difference was observed in C6/36 cells. Viral entry experiments elucidate that titer reduction likely occurred due to the diminished entry capabilities of a small-plaque isolate. Additionally, a small-plaque isolate displayed lowered neurovirulence in newborn mice compared to 100% lethality from infection with the parental ZIKV. Genomic analysis revealed the same three unique non-synonymous mutations for both small-plaque isolates: two on the envelope (E) protein at residues 310, alanine to glutamic acid (A310E), and 393, glutamic acid to lysine (E393K), and one on residue 355 of NS3, histidine to tyrosine (H355Y). Three-dimensional (3D) mapping suggests that the E protein mutations located on the receptor-binding and fusion domain III likely affect cell entry, tropism, and virulence. These ZIKV isolates and genotypic markers will be beneficial for vaccine development.