1. αVβ3 Integrin Expression Is Essential for Replication of Mosquito and Tick-Borne Flaviviruses in Murine Fibroblast Cells.
- Author
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Reis VPD, Keller M, Schmidt K, Ulrich RG, and Groschup MH
- Subjects
- Animals, Cell Line, Encephalitis Viruses, Tick-Borne genetics, Encephalitis Viruses, Tick-Borne physiology, Fibroblasts virology, Flavivirus genetics, Genome, Viral, Integrin alphaVbeta3 genetics, Mice, RNA, Viral genetics, RNA, Viral metabolism, Virus Attachment, Virus Internalization, West Nile virus genetics, West Nile virus physiology, Yellow fever virus genetics, Yellow fever virus physiology, Flavivirus physiology, Integrin alphaVbeta3 metabolism, Virus Replication
- Abstract
The Flavivirus genus includes a number of important viruses that are pathogenic to humans and animals and are responsible for outbreaks across the globe. Integrins, a family of heterodimeric transmembrane molecules expressed in all nucleated cells mediate critical functions of cell physiology and cell cycle. Integrins were previously postulated to be involved in flavivirus entry and to modulate flavivirus replication efficiency. In the present study, mouse embryonic fibroblasts (MEF), lacking the expression of αVβ3 integrin (MEF-αVβ3
-/- ), were infected with four different flaviviruses, namely yellow fever virus (YFV), West Nile virus (WNV), Usutu virus (USUV) and Langat virus (LGTV). The effects of the αVβ3 integrin absence in double-knockout MEF-αVβ3-/- on flavivirus binding, internalization and replication were compared to the respective wild-type cells. Binding to the cell surface for all four flaviviruses was not affected by the ablation of αVβ3 integrin, whereas internalization of USUV and WNV was slightly affected by the loss of αVβ3 integrin expression. Most interestingly, the deletion of αVβ3 integrin strongly impaired replication of all flaviviruses with a reduction of up to 99% on virus yields and a strong reduction on flavivirus anti-genome RNA synthesis. In conclusion, our results demonstrate that αVβ3 integrin expression in flavivirus-susceptible cell lines enhances the flavivirus replication.- Published
- 2021
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