A coupled mathematical model of the intracellular replication of Dengue virus and the host cell immune response to infection
Dengue virus (DV) is a positive-strand RNA virus of the Flavivirus genus. It is one of the most prevalent mosquito-borne viruses, with globally 390 million infected individuals per year. The clinical spectrum of DV infection ranges from an asymptomatic course to severe complications such as dengue h...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
29 April 2020
|
| In: |
Frontiers in microbiology
Year: 2020, Volume: 11 |
| ISSN: | 1664-302X |
| DOI: | 10.3389/fmicb.2020.00725 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://dx.doi.org/10.3389/fmicb.2020.00725 Verlag, lizenzpflichtig, Volltext: https://www.frontiersin.org/articles/10.3389/fmicb.2020.00725/full 
|
| Author Notes: | Carolin Zitzmann, Bianca Schmid, Alessia Ruggieri, Alan S. Perelson, Marco Binder, Ralf Bartenschlager and Lars Kaderali |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1733194320 | ||
| 003 | DE-627 | ||
| 005 | 20230427150623.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200917s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fmicb.2020.00725 |2 doi | |
| 035 | |a (DE-627)1733194320 | ||
| 035 | |a (DE-599)KXP1733194320 | ||
| 035 | |a (OCoLC)1341359705 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Zitzmann, Carolin |d 1987- |e VerfasserIn |0 (DE-588)1217791159 |0 (DE-627)1733194797 |4 aut | |
| 245 | 1 | 2 | |a A coupled mathematical model of the intracellular replication of Dengue virus and the host cell immune response to infection |c Carolin Zitzmann, Bianca Schmid, Alessia Ruggieri, Alan S. Perelson, Marco Binder, Ralf Bartenschlager and Lars Kaderali |
| 264 | 1 | |c 29 April 2020 | |
| 300 | |a 19 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 17.09.2020 | ||
| 520 | |a Dengue virus (DV) is a positive-strand RNA virus of the Flavivirus genus. It is one of the most prevalent mosquito-borne viruses, with globally 390 million infected individuals per year. The clinical spectrum of DV infection ranges from an asymptomatic course to severe complications such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), the latter because of severe plasma leakage. Given that the outcome of infection is likely determined by the kinetics of viral replication and the innate immune response (IIR) it is of importance to understand the interaction between these two parameters. In this study, we use mathematical modeling to characterize and understand the complex interplay between intracellular DV replication and the host cells’ defense mechanisms. We first measured viral RNA, viral protein, and virus particle production in Huh7 cells, which exhibit a notoriously weak intrinsic antiviral response. Based on these measurements, we developed a detailed intracellular DV replication model. We then measured replication in IFN competent A549 cells and used this data to couple the replication model with a model describing IFN activation and production of IFN stimulated genes (ISGs), as well as their interplay with DV replication. By comparing the cell line-specific DV replication, we found that host factors involved in replication complex formation and virus particle production are crucial for replication efficiency. Regarding possible modes of action of the IIR, our model fits suggest that the IIR mainly affects DV RNA translation initiation, cytosolic DV RNA degradation, and naïve cell infection. We further analyzed the potential of direct acting antiviral drugs targeting different processes of the DV lifecycle in silico and found that targeting RNA synthesis and virus assembly and release are the most promising anti-DV drug targets. | ||
| 650 | 4 | |a computational Simulation | |
| 650 | 4 | |a Dengue Virus | |
| 650 | 4 | |a innate immune response | |
| 650 | 4 | |a mathematical model | |
| 650 | 4 | |a Virus Replication | |
| 700 | 1 | |a Schmid, Bianca |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ruggieri, Alessia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Perelson, Alan S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Binder, Marco |e VerfasserIn |0 (DE-588)13571379X |0 (DE-627)69371171X |0 (DE-576)300603509 |4 aut | |
| 700 | 1 | |a Bartenschlager, Ralf |d 1958- |e VerfasserIn |0 (DE-588)1058097989 |0 (DE-627)796390509 |0 (DE-576)168706067 |4 aut | |
| 700 | 1 | |a Kaderali, Lars |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in microbiology |d Lausanne : Frontiers Media, 2010 |g 11(2020), Artikel-Nummer 725, 19 Seiten |h Online-Ressource |w (DE-627)642889384 |w (DE-600)2587354-4 |w (DE-576)335527094 |x 1664-302X |7 nnas |a A coupled mathematical model of the intracellular replication of Dengue virus and the host cell immune response to infection |
| 773 | 1 | 8 | |g volume:11 |g year:2020 |g extent:19 |a A coupled mathematical model of the intracellular replication of Dengue virus and the host cell immune response to infection |
| 856 | 4 | 0 | |u https://dx.doi.org/10.3389/fmicb.2020.00725 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.frontiersin.org/articles/10.3389/fmicb.2020.00725/full |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20200917 | ||
| 993 | |a Article | ||
| 994 | |a 2020 | ||
| 998 | |g 13571379X |a Binder, Marco |m 13571379X:Binder, Marco |d 140000 |e 140000PB13571379X |k 0/140000/ |p 6 | ||
| 998 | |g 1058097989 |a Bartenschlager, Ralf |m 1058097989:Bartenschlager, Ralf |d 910000 |d 911700 |e 910000PB1058097989 |e 911700PB1058097989 |k 0/910000/ |k 1/910000/911700/ |p 5 | ||
| 999 | |a KXP-PPN1733194320 |e 3757368983 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"title":[{"title_sort":"coupled mathematical model of the intracellular replication of Dengue virus and the host cell immune response to infection","title":"A coupled mathematical model of the intracellular replication of Dengue virus and the host cell immune response to infection"}],"person":[{"given":"Carolin","family":"Zitzmann","display":"Zitzmann, Carolin","role":"aut"},{"display":"Schmid, Bianca","family":"Schmid","given":"Bianca","role":"aut"},{"given":"Alessia","family":"Ruggieri","display":"Ruggieri, Alessia","role":"aut"},{"display":"Perelson, Alan S.","family":"Perelson","given":"Alan S.","role":"aut"},{"given":"Marco","display":"Binder, Marco","family":"Binder","role":"aut"},{"role":"aut","display":"Bartenschlager, Ralf","family":"Bartenschlager","given":"Ralf"},{"role":"aut","given":"Lars","family":"Kaderali","display":"Kaderali, Lars"}],"physDesc":[{"extent":"19 S."}],"relHost":[{"type":{"media":"Online-Ressource","bibl":"periodical"},"id":{"zdb":["2587354-4"],"issn":["1664-302X"],"eki":["642889384"]},"language":["eng"],"origin":[{"dateIssuedKey":"2010","publisher":"Frontiers Media","publisherPlace":"Lausanne","dateIssuedDisp":"2010-"}],"physDesc":[{"extent":"Online-Ressource"}],"title":[{"title":"Frontiers in microbiology","title_sort":"Frontiers in microbiology"}],"part":{"volume":"11","year":"2020","extent":"19","text":"11(2020), Artikel-Nummer 725, 19 Seiten"},"disp":"A coupled mathematical model of the intracellular replication of Dengue virus and the host cell immune response to infectionFrontiers in microbiology","recId":"642889384","pubHistory":["1.2010 -"],"note":["Gesehen am 23.12.10"]}],"id":{"eki":["1733194320"],"doi":["10.3389/fmicb.2020.00725"]},"language":["eng"],"type":{"bibl":"article-journal","media":"Online-Ressource"},"origin":[{"dateIssuedKey":"2020","dateIssuedDisp":"29 April 2020"}],"name":{"displayForm":["Carolin Zitzmann, Bianca Schmid, Alessia Ruggieri, Alan S. Perelson, Marco Binder, Ralf Bartenschlager and Lars Kaderali"]},"note":["Gesehen am 17.09.2020"],"recId":"1733194320"} | ||
| SRT | |a ZITZMANNCACOUPLEDMAT2920 | ||