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Development of a blocker of the universal phosphatidylserine- and phosphatidylethanolamine-dependent viral entry pathways.
- Source :
-
Virology [Virology] 2021 Aug; Vol. 560, pp. 17-33. Date of Electronic Publication: 2021 May 10. - Publication Year :
- 2021
-
Abstract
- Envelope phosphatidylserine (PtdSer) and phosphatidylethanolamine (PtdEtr) have been shown to mediate binding of enveloped viruses. However, commonly used PtdSer binding molecules such as Annexin V cannot block PtdSer-mediated viral infection. Lack of reagents that can conceal envelope PtdSer and PtdEtr and subsequently inhibit infection hinders elucidation of the roles of the envelope phospholipids in viral infection. Here, we developed sTIM1dMLDR801, a reagent capable of blocking PtdSer- and PtdEtr-dependent infection of enveloped viruses. Using sTIM1dMLDR801, we found that envelope PtdSer and/or PtdEtr can support ZIKV infection of not only human but also mosquito cells. In a mouse model for ZIKV infection, sTIM1dMLDR801 reduced ZIKV load in serum and the spleen, indicating envelope PtdSer and/or PtdEtr support in viral infection in vivo. sTIM1dMLDR801 will enable elucidation of the roles of envelope PtdSer and PtdEtr in infection of various virus species, thereby facilitating identification of their receptors and transmission mechanisms.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- A549 Cells
Animals
Cell Line
Chlorocebus aethiops
Culicidae virology
Female
HEK293 Cells
Humans
Intercellular Signaling Peptides and Proteins metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Proto-Oncogene Proteins metabolism
Receptor Protein-Tyrosine Kinases metabolism
Receptor, Interferon alpha-beta genetics
Vero Cells
Viral Envelope metabolism
Viral Load drug effects
Zika Virus growth & development
Zika Virus Infection drug therapy
Zika Virus Infection pathology
Zika Virus Infection transmission
Axl Receptor Tyrosine Kinase
Antiviral Agents pharmacology
Phosphatidylethanolamines antagonists & inhibitors
Phosphatidylserines antagonists & inhibitors
Virus Attachment drug effects
Virus Internalization drug effects
Zika Virus drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0341
- Volume :
- 560
- Database :
- MEDLINE
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 34020328
- Full Text :
- https://doi.org/10.1016/j.virol.2021.04.013