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Title: A New Age-Structured Multiscale Model of the Hepatitis C Virus Life-Cycle During Infection and Therapy With Direct-Acting Antiviral Agents

Here, the dynamics of hepatitis C virus (HCV) RNA during translation and replication within infected cells were added to a previous age-structured multiscale mathematical model of HCV infection and treatment. The model allows the study of the dynamics of HCV RNA inside infected cells as well as the release of virus from infected cells and the dynamics of subsequent new cell infections. The model was used to fit in vitro data and estimate parameters characterizing HCV replication. This is the first model to our knowledge to consider both positive and negative strands of HCV RNA with an age-structured multiscale modeling approach. Using this model we also studied the effects of direct-acting antiviral agents (DAAs) in blocking HCV RNA intracellular replication and the release of new virions and fit the model to in vivo data obtained from HCV-infected subjects under therapy.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [1] ;  [1] ; ORCiD logo [5]
  1. Univ. Federal de Juiz de Fora, Juiz de Fora (Brazil)
  2. The Pennsylvania State Univ., State College, PA (United States)
  3. Tulane Univ., New Orleans, LA (United States)
  4. Univ. Paris Diderot, Paris (France)
  5. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Publication Date:
Report Number(s):
LA-UR-18-20266
Journal ID: ISSN 1664-302X
Grant/Contract Number:
AC52-06NA25396
Type:
Published Article
Journal Name:
Frontiers in Microbiology
Additional Journal Information:
Journal Volume: 9; Journal ID: ISSN 1664-302X
Publisher:
Frontiers Research Foundation
Research Org:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org:
Universities/Institutions; USDOE
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Biological Science
OSTI Identifier:
1431405
Alternate Identifier(s):
OSTI ID: 1435534

Quintela, Barbara de M., Conway, Jessica M., Hyman, James M., Guedj, Jeremie, dos Santos, Rodrigo W., Lobosco, Marcelo, and Perelson, Alan S.. A New Age-Structured Multiscale Model of the Hepatitis C Virus Life-Cycle During Infection and Therapy With Direct-Acting Antiviral Agents. United States: N. p., Web. doi:10.3389/fmicb.2018.00601.
Quintela, Barbara de M., Conway, Jessica M., Hyman, James M., Guedj, Jeremie, dos Santos, Rodrigo W., Lobosco, Marcelo, & Perelson, Alan S.. A New Age-Structured Multiscale Model of the Hepatitis C Virus Life-Cycle During Infection and Therapy With Direct-Acting Antiviral Agents. United States. doi:10.3389/fmicb.2018.00601.
Quintela, Barbara de M., Conway, Jessica M., Hyman, James M., Guedj, Jeremie, dos Santos, Rodrigo W., Lobosco, Marcelo, and Perelson, Alan S.. 2018. "A New Age-Structured Multiscale Model of the Hepatitis C Virus Life-Cycle During Infection and Therapy With Direct-Acting Antiviral Agents". United States. doi:10.3389/fmicb.2018.00601.
@article{osti_1431405,
title = {A New Age-Structured Multiscale Model of the Hepatitis C Virus Life-Cycle During Infection and Therapy With Direct-Acting Antiviral Agents},
author = {Quintela, Barbara de M. and Conway, Jessica M. and Hyman, James M. and Guedj, Jeremie and dos Santos, Rodrigo W. and Lobosco, Marcelo and Perelson, Alan S.},
abstractNote = {Here, the dynamics of hepatitis C virus (HCV) RNA during translation and replication within infected cells were added to a previous age-structured multiscale mathematical model of HCV infection and treatment. The model allows the study of the dynamics of HCV RNA inside infected cells as well as the release of virus from infected cells and the dynamics of subsequent new cell infections. The model was used to fit in vitro data and estimate parameters characterizing HCV replication. This is the first model to our knowledge to consider both positive and negative strands of HCV RNA with an age-structured multiscale modeling approach. Using this model we also studied the effects of direct-acting antiviral agents (DAAs) in blocking HCV RNA intracellular replication and the release of new virions and fit the model to in vivo data obtained from HCV-infected subjects under therapy.},
doi = {10.3389/fmicb.2018.00601},
journal = {Frontiers in Microbiology},
number = ,
volume = 9,
place = {United States},
year = {2018},
month = {4}
}