The Envelope Residues E152/156/158 of Zika Virus Influence the Early Stages of Virus Infection in Human Cells
Zhao, Richard Y.
MetadataShow full item record
AbstractEmerging infections of mosquito-borne Zika virus (ZIKV) pose an increasing threat to human health, as documented over the recent years in South Pacific islands and the Americas in recent years. To better understand molecular mechanisms underlying the increase in human cases with severe pathologies, we recently demonstrated the functional roles of structural proteins capsid (C), pre-membrane (prM), and envelop (E) of ZIKV epidemic strains with the initiation of viral infection in human cells. Specifically, we found that the C-prM region contributes to permissiveness of human host cells to ZIKV infection and ZIKV-induced cytopathic effects, whereas the E protein is associated with viral attachment and early infection. In the present study, we further characterize ZIKV E proteins by investigating the roles of residues isoleucine 152 (Ile152), threonine 156 (Thr156), and histidine 158 (His158) (i.e., the E-152/156/158 residues), which surround a unique N-glycosylation site (E-154), in permissiveness of human host cells to epidemic ZIKV infection. For comparison purpose, we generated mutant molecular clones of epidemic BeH819015 (BR15) and historical MR766-NIID (MR766) strains that carry each other's E-152/156/158 residues, respectively. We observed that the BR15 mutant containing the E-152/156/158 residues from MR766 was less infectious in A549-Dual™ cells than parental virus. In contrast, the MR766 mutant containing E-152/156/158 residues from BR15 displayed increased infectivity. The observed differences in infectivity were, however, not correlated with changes in viral binding onto host-cells or cellular responses to viral infection. Instead, the E-152/156/158 residues from BR15 were associated with an increased efficiency of viral membrane fusion inside infected cells due to conformational changes of E protein that enhance exposure of the fusion loop. Our data highlight an important contribution of E-152/156/158 residues to the early steps of ZIKV infection in human cells.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/13460
- The Roles of prM-E Proteins in Historical and Epidemic Zika Virus-mediated Infection and Neurocytotoxicity.
- Authors: Li G, Bos S, Tsetsarkin KA, Pletnev AG, Desprès P, Gadea G, Zhao RY
- Issue date: 2019 Feb 14
- Envelope Protein Glycosylation Mediates Zika Virus Pathogenesis.
- Authors: Carbaugh DL, Baric RS, Lazear HM
- Issue date: 2019 Jun 15
- Zika Virus Encoding Nonglycosylated Envelope Protein Is Attenuated and Defective in Neuroinvasion.
- Authors: Annamalai AS, Pattnaik A, Sahoo BR, Muthukrishnan E, Natarajan SK, Steffen D, Vu HLX, Delhon G, Osorio FA, Petro TM, Xiang SH, Pattnaik AK
- Issue date: 2017 Dec 1
- The structural proteins of epidemic and historical strains of Zika virus differ in their ability to initiate viral infection in human host cells.
- Authors: Bos S, Viranaicken W, Turpin J, El-Kalamouni C, Roche M, Krejbich-Trotot P, Desprès P, Gadea G
- Issue date: 2018 Mar
- Zika Virus NS2A-Mediated Virion Assembly.
- Authors: Zhang X, Xie X, Xia H, Zou J, Huang L, Popov VL, Chen X, Shi PY
- Issue date: 2019 Oct 29