A Small-Plaque Isolate of the Zika Virus with Envelope Domain III Mutations Affect Viral Entry and Replication in Mammalian but Not Mosquito Cells

Bibliographic Details
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
Authors: Thitigun Jaimipuk, Saranya Sachdev, Sutee Yoksan, Chutima Thepparit
Source: Viruses, Vol 14, Iss 3, p 480 (2022)
Publisher Information: MDPI AG, 2022.
Publication Year: 2022
Collection: LCC:Microbiology
Subject Terms: Zika virus, attenuation, cell tropism, NS3, E protein, vaccine, Microbiology, QR1-502
More Details: 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 small-plaque 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1999-4915
Relation: https://www.mdpi.com/1999-4915/14/3/480; https://doaj.org/toc/1999-4915
DOI: 10.3390/v14030480
Access URL: https://doaj.org/article/3aaee0ee938a4cea8949d609b54b9151
Accession Number: edsdoj.3aaee0ee938a4cea8949d609b54b9151
Database: Directory of Open Access Journals
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More Details
ISSN:19994915
DOI:10.3390/v14030480
Published in:Viruses
Language:English