Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies
Abstract
Plus-strand RNA viruses are the largest group of viruses. Many are human pathogens that inflict a socio-economic burden. Interestingly, plus-strand RNA viruses share remarkable similarities in their replication. A hallmark of plus-strand RNA viruses is the remodeling of intracellular membranes to establish replication organelles (so-called “replication factories”), which provide a protected environment for the replicase complex, consisting of the viral genome and proteins necessary for viral RNA synthesis. In the current study, we investigate pan-viral similarities and virus-specific differences in the life cycle of this highly relevant group of viruses. We first measured the kinetics of viral RNA, viral protein, and infectious virus particle production of hepatitis C virus (HCV), dengue virus (DENV), and coxsackievirus B3 (CVB3) in the immuno-compromised Huh7 cell line and thus without perturbations by an intrinsic immune response. Based on these measurements, we developed a detailed mathematical model of the replication of HCV, DENV, and CVB3 and showed that only small virus-specific changes in the model were necessary to describe the in vitro dynamics of the different viruses. Our model correctly predicted virus-specific mechanisms such as host cell translation shut off and different kinetics of replication organelles. Further, our model suggests that the ability to suppressmore »
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE National Nuclear Security Administration (NNSA); Federal Ministry of Education and Research ( BMBF ); German Research Foundation (DFG); German Cancer Research Center (DKFZ); National Institutes of Health (NIH)
- OSTI Identifier:
- 1970049
- Alternate Identifier(s):
- OSTI ID: 1968339; OSTI ID: 1975019
- Report Number(s):
- LA-UR-22-21450
Journal ID: ISSN 1553-7358; 10.1371/journal.pcbi.1010423
- Grant/Contract Number:
- 89233218CNA000001; R01-AI078881, and R01-AI116868; 031A602A; KA 2989/13-1; R01-AI078881; R01-AI116868
- Resource Type:
- Published Article
- Journal Name:
- PLoS Computational Biology (Online)
- Additional Journal Information:
- Journal Name: PLoS Computational Biology (Online) Journal Volume: 19 Journal Issue: 4; Journal ID: ISSN 1553-7358
- Publisher:
- Public Library of Science (PLoS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 97 MATHEMATICS AND COMPUTING; dengue virus; protein translation; viral replication; RNA viruses; hepatitis C virus; ribosomes; RNA synthesis; life cycles
Citation Formats
Zitzmann, Carolin, Dächert, Christopher, Schmid, Bianca, van der Schaar, Hilde, van Hemert, Martijn, Perelson, Alan S., van Kuppeveld, Frank J. M., Bartenschlager, Ralf, Binder, Marco, Kaderali, Lars, and Kasson, ed., Peter M. Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies. United States: N. p., 2023.
Web. doi:10.1371/journal.pcbi.1010423.
Zitzmann, Carolin, Dächert, Christopher, Schmid, Bianca, van der Schaar, Hilde, van Hemert, Martijn, Perelson, Alan S., van Kuppeveld, Frank J. M., Bartenschlager, Ralf, Binder, Marco, Kaderali, Lars, & Kasson, ed., Peter M. Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies. United States. https://doi.org/10.1371/journal.pcbi.1010423
Zitzmann, Carolin, Dächert, Christopher, Schmid, Bianca, van der Schaar, Hilde, van Hemert, Martijn, Perelson, Alan S., van Kuppeveld, Frank J. M., Bartenschlager, Ralf, Binder, Marco, Kaderali, Lars, and Kasson, ed., Peter M. Tue .
"Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies". United States. https://doi.org/10.1371/journal.pcbi.1010423.
@article{osti_1970049,
title = {Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies},
author = {Zitzmann, Carolin and Dächert, Christopher and Schmid, Bianca and van der Schaar, Hilde and van Hemert, Martijn and Perelson, Alan S. and van Kuppeveld, Frank J. M. and Bartenschlager, Ralf and Binder, Marco and Kaderali, Lars and Kasson, ed., Peter M.},
abstractNote = {Plus-strand RNA viruses are the largest group of viruses. Many are human pathogens that inflict a socio-economic burden. Interestingly, plus-strand RNA viruses share remarkable similarities in their replication. A hallmark of plus-strand RNA viruses is the remodeling of intracellular membranes to establish replication organelles (so-called “replication factories”), which provide a protected environment for the replicase complex, consisting of the viral genome and proteins necessary for viral RNA synthesis. In the current study, we investigate pan-viral similarities and virus-specific differences in the life cycle of this highly relevant group of viruses. We first measured the kinetics of viral RNA, viral protein, and infectious virus particle production of hepatitis C virus (HCV), dengue virus (DENV), and coxsackievirus B3 (CVB3) in the immuno-compromised Huh7 cell line and thus without perturbations by an intrinsic immune response. Based on these measurements, we developed a detailed mathematical model of the replication of HCV, DENV, and CVB3 and showed that only small virus-specific changes in the model were necessary to describe the in vitro dynamics of the different viruses. Our model correctly predicted virus-specific mechanisms such as host cell translation shut off and different kinetics of replication organelles. Further, our model suggests that the ability to suppress or shut down host cell mRNA translation may be a key factor for in vitro replication efficiency, which may determine acute self-limited or chronic infection. We further analyzed potential broad-spectrum antiviral treatment options in silico and found that targeting viral RNA translation, such as polyprotein cleavage and viral RNA synthesis, may be the most promising drug targets for all plus-strand RNA viruses. Moreover, we found that targeting only the formation of replicase complexes did not stop the in vitro viral replication early in infection, while inhibiting intracellular trafficking processes may even lead to amplified viral growth.},
doi = {10.1371/journal.pcbi.1010423},
journal = {PLoS Computational Biology (Online)},
number = 4,
volume = 19,
place = {United States},
year = {Tue Apr 04 00:00:00 EDT 2023},
month = {Tue Apr 04 00:00:00 EDT 2023}
}
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Works referenced in this record:
High-throughput approaches to unravel hepatitis C virus-host interactions
journal, June 2016
- Colpitts, Che C.; El-Saghire, Hussein; Pochet, Nathalie
- Virus Research, Vol. 218
Quantitative analysis of viral RNA kinetics in coxsackievirus B3-induced murine myocarditis: biphasic pattern of clearance following acute infection, with persistence of residual viral RNA throughout and beyond the inflammatory phase of disease
journal, November 2000
- Reetoo, K. Nundita; Osman, Shabina A.; Illavia, Shirin J.
- Journal of General Virology, Vol. 81, Issue 11
Revealing enterovirus infection in chronic human disorders: An integrated diagnostic approach
journal, July 2017
- Genoni, Angelo; Canducci, Filippo; Rossi, Agostino
- Scientific Reports, Vol. 7, Issue 1
A methodology for performing global uncertainty and sensitivity analysis in systems biology
journal, September 2008
- Marino, Simeone; Hogue, Ian B.; Ray, Christian J.
- Journal of Theoretical Biology, Vol. 254, Issue 1
Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in chimpanzees
journal, January 2004
- Major, Marian E.; Dahari, Harel; Mihalik, Kathleen
- Hepatology, Vol. 39, Issue 6
Intracellular Localization of Poliovirus Plus- and Minus-Strand RNA Visualized by Strand-Specific Fluorescent In Situ Hybridization
journal, November 1998
- Bolten, Roger; Egger, Denise; Gosert, Rainer
- Journal of Virology, Vol. 72, Issue 11
Mathematical modeling of viral kinetics:
journal, February 2003
- Layden, Thomas J.; Layden, Jennifer E.; Ribeiro, Ruy M.
- Clinics in Liver Disease, Vol. 7, Issue 1
Quantitative Intracellular Kinetics of HIV Type 1
journal, February 1999
- Reddy, Bindu; Yin, John
- AIDS Research and Human Retroviruses, Vol. 15, Issue 3
Modeling the complete kinetics of coxsackievirus B3 reveals human determinants of host-cell feedback
journal, April 2021
- Lopacinski, Aaron B.; Sweatt, Andrew J.; Smolko, Christian M.
- Cell Systems, Vol. 12, Issue 4
Recent Advances in Deciphering Viral and Host Determinants of Dengue Virus Replication and Pathogenesis
journal, August 2006
- Clyde, Karen; Kyle, Jennifer L.; Harris, Eva
- Journal of Virology, Vol. 80, Issue 23
Intracellular Hepatitis C Virus Modeling Predicts Infection Dynamics and Viral Protein Mechanisms
journal, June 2018
- Aunins, Thomas R.; Marsh, Katherine A.; Subramanya, Gitanjali
- Journal of Virology, Vol. 92, Issue 11
The life cycle of non-polio enteroviruses and how to target it
journal, April 2018
- Baggen, Jim; Thibaut, Hendrik Jan; Strating, Jeroen R. P. M.
- Nature Reviews Microbiology, Vol. 16, Issue 6
Infection by Zika viruses requires the transmembrane protein AXL, endocytosis and low pH
journal, May 2018
- Persaud, Mirjana; Martinez-Lopez, Alicia; Buffone, Cindy
- Virology, Vol. 518
Attenuation of 40S Ribosomal Subunit Abundance Differentially Affects Host and HCV Translation and Suppresses HCV Replication
journal, June 2012
- Huang, Jing-Ying; Su, Wen-Chi; Jeng, King-Song
- PLoS Pathogens, Vol. 8, Issue 6
Translational Control of Viral Gene Expression in Eukaryotes
journal, June 2000
- Gale, Michael; Tan, Seng-Lai; Katze, Michael G.
- Microbiology and Molecular Biology Reviews, Vol. 64, Issue 2
Decay characteristics of HIV-1-infected compartments during combination therapy
journal, May 1997
- Perelson, Alan S.; Essunger, Paulina; Cao, Yunzhen
- Nature, Vol. 387, Issue 6629
Mathematical modeling of hepatitis C RNA replication, exosome secretion and virus release
journal, November 2020
- Zitzmann, Carolin; Kaderali, Lars; Perelson, Alan S.
- PLOS Computational Biology, Vol. 16, Issue 11
Cyclophilin A Associates with Enterovirus-71 Virus Capsid and Plays an Essential Role in Viral Infection as an Uncoating Regulator
journal, October 2014
- Qing, Jie; Wang, Yaxin; Sun, Yuna
- PLoS Pathogens, Vol. 10, Issue 10
Three-Dimensional Architecture and Biogenesis of Membrane Structures Associated with Hepatitis C Virus Replication
journal, December 2012
- Romero-Brey, Inés; Merz, Andreas; Chiramel, Abhilash
- PLoS Pathogens, Vol. 8, Issue 12
SARS-CoV-2 uses a multipronged strategy to impede host protein synthesis
journal, May 2021
- Finkel, Yaara; Gluck, Avi; Nachshon, Aharon
- Nature, Vol. 594, Issue 7862
Quantifying the Diversification of Hepatitis C Virus (HCV) during Primary Infection: Estimates of the In Vivo Mutation Rate
journal, August 2012
- Ribeiro, Ruy M.; Li, Hui; Wang, Shuyi
- PLoS Pathogens, Vol. 8, Issue 8
Multiscale Modeling of Influenza A Virus Infection Supports the Development of Direct-Acting Antivirals
journal, November 2013
- Heldt, Frank S.; Frensing, Timo; Pflugmacher, Antje
- PLoS Computational Biology, Vol. 9, Issue 11
Dengue Virus NS1 Uses Scavenger Receptor B1 as a Cell Receptor in Cultured Cells
journal, March 2022
- Alcalá, Ana C.; Maravillas, José L.; Meza, David
- Journal of Virology, Vol. 96, Issue 5
Replication of respiratory viruses, particularly influenza virus, rhinovirus, and coronavirus in HuH7 hepatocarcinoma cell line
journal, January 2005
- Freymuth, François; Vabret, Astrid; Rozenberg, Flore
- Journal of Medical Virology, Vol. 77, Issue 2
Modeling the Intracellular Dynamics of Influenza Virus Replication To Understand the Control of Viral RNA Synthesis
journal, May 2012
- Heldt, F. S.; Frensing, T.; Reichl, U.
- Journal of Virology, Vol. 86, Issue 15
A Recombinant Hepatitis C Virus RNA-Dependent RNA Polymerase Capable of Copying the Full-Length Viral RNA
journal, September 1999
- Oh, Jong-Won; Ito, Takayoshi; Lai, Michael M. C.
- Journal of Virology, Vol. 73, Issue 9
The Organizing Principles of Eukaryotic Ribosome Recruitment
journal, June 2019
- Pelletier, Jerry; Sonenberg, Nahum
- Annual Review of Biochemistry, Vol. 88, Issue 1
Quantitation of HCV RNA in liver of patients with chronic hepatitis C
journal, October 2000
- Martinelli, Ana de Lôurdes Candolo; Brown, David; Morris, Allun
- Arquivos de Gastroenterologia, Vol. 37, Issue 4
RACK1 Controls IRES-Mediated Translation of Viruses
journal, November 2014
- Majzoub, Karim; Hafirassou, Mohamed Lamine; Meignin, Carine
- Cell, Vol. 159, Issue 5
Spending on Hepatitis C Antivirals in the United States and Canada, 2014 to 2018
journal, September 2020
- Shakeri, Ahmad; Srimurugathasan, Narthaanan; Suda, Katie J.
- Value in Health, Vol. 23, Issue 9
Regulating Intracellular Antiviral Defense and Permissiveness to Hepatitis C Virus RNA Replication through a Cellular RNA Helicase, RIG-I
journal, March 2005
- Sumpter, Rhea; Loo, Yueh-Ming; Foy, Eileen
- Journal of Virology, Vol. 79, Issue 5
Data2Dynamics: a modeling environment tailored to parameter estimation in dynamical systems: Fig. 1.
journal, July 2015
- Raue, A.; Steiert, B.; Schelker, M.
- Bioinformatics, Vol. 31, Issue 21
RACK1 mediates rewiring of intracellular networks induced by hepatitis C virus infection
journal, September 2019
- Lee, Jae Seung; Tabata, Keisuke; Twu, Woan-Ing
- PLOS Pathogens, Vol. 15, Issue 9
Ultrastructural Characterization of Zika Virus Replication Factories
journal, February 2017
- Cortese, Mirko; Goellner, Sarah; Acosta, Eliana Gisela
- Cell Reports, Vol. 18, Issue 9
Translation and Replication Dynamics of Single RNA Viruses
journal, December 2020
- Boersma, Sanne; Rabouw, Huib H.; Bruurs, Lucas J. M.
- Cell, Vol. 183, Issue 7
MDA5 Detects the Double-Stranded RNA Replicative Form in Picornavirus-Infected Cells
journal, November 2012
- Feng, Qian; Hato, Stanleyson V.; Langereis, Martijn A.
- Cell Reports, Vol. 2, Issue 5
Structured model of influenza virus replication in MDCK cells
journal, January 2004
- Sidorenko, Y.; Reichl, U.
- Biotechnology and Bioengineering, Vol. 88, Issue 1
Origins of Enterovirus Replication Organelles Established by Whole-Cell Electron Microscopy
journal, June 2019
- Melia, Charlotte E.; Peddie, Christopher J.; de Jong, Anja W. M.
- mBio, Vol. 10, Issue 3
Modeling the intracellular replication of influenza A virus in the presence of defective interfering RNAs
journal, February 2016
- Laske, Tanja; Heldt, Frank Stefan; Hoffmann, Helene
- Virus Research, Vol. 213
Kinetic Analyses Reveal Potent and Early Blockade of Hepatitis C Virus Assembly by NS5A Inhibitors
journal, August 2014
- McGivern, David R.; Masaki, Takahiro; Williford, Sara
- Gastroenterology, Vol. 147, Issue 2
The Internal Ribosome Entry Site of Dengue Virus mRNA Is Active When Cap-Dependent Translation Initiation Is Inhibited
journal, February 2021
- Fernández-García, Leandro; Angulo, Jenniffer; Ramos, Hade
- Journal of Virology, Vol. 95, Issue 5
Basic reproduction number of coxsackievirus type A6 and A16 and enterovirus 71: estimates from outbreaks of hand, foot and mouth disease in Singapore, a tropical city-state
journal, September 2015
- Lim, C. T. K.; Jiang, L.; Ma, S.
- Epidemiology and Infection, Vol. 144, Issue 5
Hepatitis B Virus Kinetics and Mathematical Modeling
journal, February 2004
- Perelson, Alan S.; Ribeiro, Ruy M.
- Seminars in Liver Disease, Vol. 24
COVID-19 Outbreak: An Overview
journal, January 2019
- Ciotti, Marco; Angeletti, Silvia; Minieri, Marilena
- Chemotherapy, Vol. 64, Issue 5-6
Inhibition of native hepatitis C virus replicase by nucleotide and non-nucleoside inhibitors
journal, February 2005
- Ma, Han; Leveque, Vincent; De Witte, Anniek
- Virology, Vol. 332, Issue 1
Dengue Virus- and Hepatitis C Virus-Induced Replication and Assembly Compartments: the Enemy Inside--Caught in the Web
journal, March 2014
- Chatel-Chaix, L.; Bartenschlager, R.
- Journal of Virology, Vol. 88, Issue 11
NS5A inhibitors unmask differences in functional replicase complex half-life between different hepatitis C virus strains
journal, June 2017
- Benzine, Tiffany; Brandt, Ryan; Lovell, William C.
- PLOS Pathogens, Vol. 13, Issue 6
Life cycle process dependencies of positive-sense RNA viruses suggest strategies for inhibiting productive cellular infection
journal, November 2021
- Chhajer, Harsh; Rizvi, Vaseef A.; Roy, Rahul
- Journal of The Royal Society Interface, Vol. 18, Issue 184
Current therapeutics against HCV
journal, June 2021
- Bhattacharjee, Chayan; Singh, Maitri; Das, Debisukti
- VirusDisease, Vol. 32, Issue 2
Human immunodeficiency virus drug therapy and virus load
journal, April 1997
- Bonhoeffer, S.; Coffin, J. M.; Nowak, M. A.
- Journal of Virology, Vol. 71, Issue 4
Kinetics of Influenza A Virus Infection in Humans
journal, July 2006
- Baccam, P.; Beauchemin, C.; Macken, C. A.
- Journal of Virology, Vol. 80, Issue 15
Transmission-clearance trade-offs indicate that dengue virulence evolution depends on epidemiological context
journal, June 2018
- Ben-Shachar, Rotem; Koelle, Katia
- Nature Communications, Vol. 9, Issue 1
Influenza A virus infection kinetics: quantitative data and models: Modeling influenza kinetics
journal, December 2010
- Smith, Amber M.; Perelson, Alan S.
- Wiley Interdisciplinary Reviews: Systems Biology and Medicine, Vol. 3, Issue 4
Hepatitis C Virus Genotypes and Viral Concentrations in Participants of a General Population Survey in the United States
journal, August 2006
- Nainan, Omana V.; Alter, Miriam J.; Kruszon-Moran, Deanna
- Gastroenterology, Vol. 131, Issue 2
(+)RNA viruses rewire cellular pathways to build replication organelles
journal, December 2012
- Belov, George A.; van Kuppeveld, Frank JM
- Current Opinion in Virology, Vol. 2, Issue 6
Escaping Host Factor PI4KB Inhibition: Enterovirus Genomic RNA Replication in the Absence of Replication Organelles
journal, October 2017
- Melia, Charlotte E.; van der Schaar, Hilde M.; Lyoo, Heyrhyoung
- Cell Reports, Vol. 21, Issue 3
A New Age-Structured Multiscale Model of the Hepatitis C Virus Life-Cycle During Infection and Therapy With Direct-Acting Antiviral Agents
journal, April 2018
- Quintela, Barbara de M.; Conway, Jessica M.; Hyman, James M.
- Frontiers in Microbiology, Vol. 9
Evaluation of a range of mammalian and mosquito cell lines for use in Chikungunya virus research
journal, November 2017
- Roberts, Grace C.; Zothner, Carsten; Remenyi, Roland
- Scientific Reports, Vol. 7, Issue 1
Hepatic damage associated with dengue-2 virus replication in liver cells of BALB/c mice
journal, October 2009
- Paes, Marciano Viana; Lenzi, Henrique Leonel; Nogueira, Ana Cristina Martins
- Laboratory Investigation, Vol. 89, Issue 10
Poliovirus 2A Protease Triggers a Selective Nucleo-Cytoplasmic Redistribution of Splicing Factors to Regulate Alternative Pre-mRNA Splicing
journal, September 2013
- Álvarez, Enrique; Castelló, Alfredo; Carrasco, Luis
- PLoS ONE, Vol. 8, Issue 9
Gene Expression Profiling of Different Huh7 Variants Reveals Novel Hepatitis C Virus Host Factors
journal, December 2019
- Dächert, Christopher; Gladilin, Evgeny; Binder, Marco
- Viruses, Vol. 12, Issue 1
The global economic burden of dengue: a systematic analysis
journal, August 2016
- Shepard, Donald S.; Undurraga, Eduardo A.; Halasa, Yara A.
- The Lancet Infectious Diseases, Vol. 16, Issue 8
Morphological and Biochemical Characterization of the Membranous Hepatitis C Virus Replication Compartment
journal, July 2013
- Paul, D.; Hoppe, S.; Saher, G.
- Journal of Virology, Vol. 87, Issue 19
New Small-Molecule Inhibitors Effectively Blocking Picornavirus Replication
journal, October 2014
- Ford Siltz, Lauren A.; Viktorova, Ekaterina G.; Zhang, Ben
- Journal of Virology, Vol. 88, Issue 19
Infection of five human liver cell lines by dengue-2 virus
journal, April 2000
- Lin, Yin-Ling; Liu, Ching-Chuan; Lei, Huan-Yao
- Journal of Medical Virology, Vol. 60, Issue 4
MOPS and coxsackievirus B3 stability
journal, January 2017
- Carson, Steven D.; Hafenstein, Susan; Lee, Hyunwook
- Virology, Vol. 501
Architecture and biogenesis of plus-strand RNA virus replication factories
journal, January 2013
- Paul, David
- World Journal of Virology, Vol. 2, Issue 2
The Pathology of Severe Dengue in Multiple Organs of Human Fatal Cases: Histopathology, Ultrastructure and Virus Replication
journal, April 2014
- Póvoa, Tiago F.; Alves, Ada M. B.; Oliveira, Carlos A. B.
- PLoS ONE, Vol. 9, Issue 4
Mathematical Analysis of Viral Replication Dynamics and Antiviral Treatment Strategies: From Basic Models to Age-Based Multi-Scale Modeling
journal, July 2018
- Zitzmann, Carolin; Kaderali, Lars
- Frontiers in Microbiology, Vol. 9
Optimal Replication of Poliovirus within Cells
journal, March 2005
- Regoes, Roland R.; Crotty, Shane; Antia, Rustom
- The American Naturalist, Vol. 165, Issue 3
A balance between circular and linear forms of the dengue virus genome is crucial for viral replication
journal, October 2010
- Villordo, Sergio M.; Alvarez, Diego E.; Gamarnik, Andrea V.
- RNA, Vol. 16, Issue 12
Recombinant Dengue Type 1 Virus NS5 Protein Expressed inEscherichia coliExhibits RNA-Dependent RNA Polymerase Activity
journal, February 1996
- Tan, Boon-Huan; Fu, Jianlin; Sugrue, Richard J.
- Virology, Vol. 216, Issue 2
Variations of Coxsackievirus B3 Capsid Primary Structure, Ligands, and Stability Are Selected for in a Coxsackievirus and Adenovirus Receptor-Limited Environment
journal, April 2011
- Carson, Steven D.; Chapman, Nora M.; Hafenstein, Susan
- Journal of Virology, Vol. 85, Issue 7
GBF1, a Guanine Nucleotide Exchange Factor for Arf, Is Crucial for Coxsackievirus B3 RNA Replication
journal, November 2009
- Lanke, Kjerstin H. W.; van der Schaar, Hilde M.; Belov, George A.
- Journal of Virology, Vol. 83, Issue 22
Price of a hepatitis C cure: Cost of production and current prices for direct-acting antivirals in 50 countries
journal, September 2020
- Barber, Melissa J.; Gotham, Dzintars; Khwairakpam, Giten
- Journal of Virus Eradication, Vol. 6, Issue 3
Hepatitis C Virus RNA Replication Depends on Specific Cis- and Trans-Acting Activities of Viral Nonstructural Proteins
journal, April 2015
- Kazakov, Teymur; Yang, Feng; Ramanathan, Harish N.
- PLOS Pathogens, Vol. 11, Issue 4
Anti-Hepatitis C Virus Activity and Toxicity of Type III Phosphatidylinositol-4-Kinase Beta Inhibitors
journal, October 2012
- LaMarche, M. J.; Borawski, J.; Bose, A.
- Antimicrobial Agents and Chemotherapy, Vol. 56, Issue 10
The dependence of viral RNA replication on co-opted host factors
journal, December 2011
- Nagy, Peter D.; Pogany, Judit
- Nature Reviews Microbiology, Vol. 10, Issue 2
Live Cell Analysis and Mathematical Modeling Identify Determinants of Attenuation of Dengue Virus 2’-O-Methylation Mutant
journal, December 2015
- Schmid, Bianca; Rinas, Melanie; Ruggieri, Alessia
- PLOS Pathogens, Vol. 11, Issue 12
The decrease in size and synthetic activity of poliovirus polysomes late in the infectious cycle
journal, March 1967
- Summers, Donald F.; Maizel, Jacob V.; Darnell, James E.
- Virology, Vol. 31, Issue 3
Direct-acting antivirals and host-targeting strategies to combat enterovirus infections
journal, June 2017
- Bauer, Lisa; Lyoo, Heyrhyoung; van der Schaar, Hilde M.
- Current Opinion in Virology, Vol. 24
Replication Vesicles are Load- and Choke-Points in the Hepatitis C Virus Lifecycle
journal, August 2013
- Binder, Marco; Sulaimanov, Nurgazy; Clausznitzer, Diana
- PLoS Pathogens, Vol. 9, Issue 8
Secretion of Hepatitis C Virus Replication Intermediates Reduces Activation of Toll-Like Receptor 3 in Hepatocytes
journal, June 2018
- Grünvogel, Oliver; Colasanti, Ombretta; Lee, Ji-Young
- Gastroenterology, Vol. 154, Issue 8
Exploitation of cellular pathways by Dengue virus
journal, August 2011
- Fischl, Wolfgang; Bartenschlager, Ralf
- Current Opinion in Microbiology, Vol. 14, Issue 4
Viral Reorganization of the Secretory Pathway Generates Distinct Organelles for RNA Replication
journal, May 2010
- Hsu, Nai-Yun; Ilnytska, Olha; Belov, Georgiy
- Cell, Vol. 141, Issue 5
IRES-mediated cap-independent translation, a path leading to hidden proteome
journal, September 2019
- Yang, Yun; Wang, Zefeng
- Journal of Molecular Cell Biology, Vol. 11, Issue 10
The Level of CD81 Cell Surface Expression Is a Key Determinant for Productive Entry of Hepatitis C Virus into Host Cells
journal, January 2007
- Koutsoudakis, George; Herrmann, Eva; Kallis, Stephanie
- Journal of Virology, Vol. 81, Issue 2
Estimation of the Basic Reproduction Number of Enterovirus 71 and Coxsackievirus A16 in Hand, Foot, and Mouth Disease Outbreaks
journal, August 2011
- Ma, Edmond; Fung, Connie; Yip, Steven H. L.
- Pediatric Infectious Disease Journal, Vol. 30, Issue 8
Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study
journal, May 2020
- Chu, Hin; Chan, Jasper Fuk-Woo; Yuen, Terrence Tsz-Tai
- The Lancet Microbe, Vol. 1, Issue 1
A Randomized, Double-Blind, Placebo-Controlled Trial of Pleconaril for the Treatment of Neonates With Enterovirus Sepsis
journal, April 2015
- Abzug, Mark J.; Michaels, Marian G.; Wald, Ellen
- Journal of the Pediatric Infectious Diseases Society, Vol. 5, Issue 1
Dengue Virus Pathogenesis: an Integrated View
journal, October 2009
- Martina, Byron E. E.; Koraka, Penelope; Osterhaus, Albert D. M. E.
- Clinical Microbiology Reviews, Vol. 22, Issue 4
A Coupled Mathematical Model of the Intracellular Replication of Dengue Virus and the Host Cell Immune Response to Infection
journal, April 2020
- Zitzmann, Carolin; Schmid, Bianca; Ruggieri, Alessia
- Frontiers in Microbiology, Vol. 11
An RNA hairpin at the extreme 5' end of the poliovirus RNA genome modulates viral translation in human cells
journal, February 1991
- Simoes, E. A.; Sarnow, P.
- Journal of Virology, Vol. 65, Issue 2
Differential replicative fitness of the four dengue virus serotypes circulating in Colombia in human liver Huh7 cells
journal, January 2020
- Gutiérrez-Barbosa, Hernando; Castañeda, Nadia Y.; Castellanos, Jaime E.
- The Brazilian Journal of Infectious Diseases, Vol. 24, Issue 1
Modeling the within-host dynamics of HIV infection
journal, September 2013
- Perelson, Alan S.; Ribeiro, Ruy M.
- BMC Biology, Vol. 11, Issue 1
Modification of intracellular membrane structures for virus replication
journal, May 2008
- Miller, Sven; Krijnse-Locker, Jacomine
- Nature Reviews Microbiology, Vol. 6, Issue 5
Patterns of Hepatitis C Virus RNA Levels during Acute Infection: The InC3 Study
journal, April 2015
- Hajarizadeh, Behzad; Grady, Bart; Page, Kimberly
- PLOS ONE, Vol. 10, Issue 4
Convergent use of phosphatidic acid for hepatitis C virus and SARS-CoV-2 replication organelle formation
journal, December 2021
- Tabata, Keisuke; Prasad, Vibhu; Paul, David
- Nature Communications, Vol. 12, Issue 1
Single-cell analysis and stochastic modelling unveil large cell-to-cell variability in influenza A virus infection
journal, November 2015
- Heldt, Frank S.; Kupke, Sascha Y.; Dorl, Sebastian
- Nature Communications, Vol. 6, Issue 1
Poliovirus RNA-Dependent RNA Polymerase (3D pol ): Kinetic, Thermodynamic, and Structural Analysis of Ribonucleotide Selection †
journal, May 2004
- Gohara, David W.; Arnold, Jamie J.; Cameron, Craig E.
- Biochemistry, Vol. 43, Issue 18
Continuous Influenza Virus Production in Cell Culture Shows a Periodic Accumulation of Defective Interfering Particles
journal, September 2013
- Frensing, Timo; Heldt, Frank Stefan; Pflugmacher, Antje
- PLoS ONE, Vol. 8, Issue 9
Interferon-beta expression and type I interferon receptor signaling of hepatocytes prevent hepatic necrosis and virus dissemination in Coxsackievirus B3-infected mice
journal, August 2018
- Koestner, Wolfgang; Spanier, Julia; Klause, Tanja
- PLOS Pathogens, Vol. 14, Issue 8
Structural and practical identifiability analysis of partially observed dynamical models by exploiting the profile likelihood
journal, June 2009
- Raue, A.; Kreutz, C.; Maiwald, T.
- Bioinformatics, Vol. 25, Issue 15
Human stem cell-derived hepatocyte-like cells support Zika virus replication and provide a relevant model to assess the efficacy of potential antivirals
journal, December 2018
- Tricot, Tine; Helsen, Nicky; Kaptein, Suzanne J. F.
- PLOS ONE, Vol. 13, Issue 12
A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors
journal, December 2017
- Hafirassou, Mohamed Lamine; Meertens, Laurent; Umaña-Diaz, Claudia
- Cell Reports, Vol. 21, Issue 13
On the History of Hepatitis C Virus Cell Culture Systems
journal, November 2013
- Lohmann, Volker; Bartenschlager, Ralf
- Journal of Medicinal Chemistry, Vol. 57, Issue 5
Current Trends and Limitations in Dengue Antiviral Research
journal, September 2021
- Obi, Juliet; Gutiérrez-Barbosa, Hernando; Chua, Joel
- Tropical Medicine and Infectious Disease, Vol. 6, Issue 4
A pan-serotype dengue virus inhibitor targeting the NS3–NS4B interaction
journal, October 2021
- Kaptein, Suzanne J. F.; Goethals, Olivia; Kiemel, Dominik
- Nature, Vol. 598, Issue 7881