αVβ3 Integrin Expression Is Essential for Replication of Mosquito and Tick-Borne Flaviviruses in Murine Fibroblast Cells
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
|---|---|
| Enthalten in: |
Viruses - 14(2021), 1 vom: 23. Dez. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Reis, Vinicius Pinho Dos [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Flavivirus |
|---|
| Anmerkungen: |
Date Completed 18.02.2022 Date Revised 18.02.2022 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/v14010018 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM335968147 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM335968147 | ||
| 003 | DE-627 | ||
| 005 | 20231225231050.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/v14010018 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1119.xml |
| 035 | |a (DE-627)NLM335968147 | ||
| 035 | |a (NLM)35062222 | ||
| 035 | |a (PII)18 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Reis, Vinicius Pinho Dos |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a αVβ3 Integrin Expression Is Essential for Replication of Mosquito and Tick-Borne Flaviviruses in Murine Fibroblast Cells |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 18.02.2022 | ||
| 500 | |a Date Revised 18.02.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a flavivirus | |
| 650 | 4 | |a host cell factors | |
| 650 | 4 | |a integrins | |
| 650 | 4 | |a virus binding | |
| 650 | 4 | |a virus internalization | |
| 650 | 4 | |a virus replication | |
| 650 | 7 | |a Integrin alphaVbeta3 |2 NLM | |
| 650 | 7 | |a RNA, Viral |2 NLM | |
| 700 | 1 | |a Keller, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Schmidt, Katja |e verfasserin |4 aut | |
| 700 | 1 | |a Ulrich, Rainer Günter |e verfasserin |4 aut | |
| 700 | 1 | |a Groschup, Martin Hermann |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Viruses |d 2009 |g 14(2021), 1 vom: 23. Dez. |w (DE-627)NLM192382764 |x 1999-4915 |7 nnns |
| 773 | 1 | 8 | |g volume:14 |g year:2021 |g number:1 |g day:23 |g month:12 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/v14010018 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 14 |j 2021 |e 1 |b 23 |c 12 | ||