SARS-CoV-2 viral dynamics in non-human primates.


Journal

PLoS computational biology
ISSN: 1553-7358
Titre abrégé: PLoS Comput Biol
Pays: United States
ID NLM: 101238922

Informations de publication

Date de publication:
03 2021
Historique:
received: 16 09 2020
accepted: 11 02 2021
revised: 29 03 2021
pubmed: 18 3 2021
medline: 15 4 2021
entrez: 17 3 2021
Statut: epublish

Résumé

Non-human primates infected with SARS-CoV-2 exhibit mild clinical signs. Here we used a mathematical model to characterize in detail the viral dynamics in 31 cynomolgus macaques for which nasopharyngeal and tracheal viral load were frequently assessed. We identified that infected cells had a large burst size (>104 virus) and a within-host reproductive basic number of approximately 6 and 4 in nasopharyngeal and tracheal compartment, respectively. After peak viral load, infected cells were rapidly lost with a half-life of 9 hours, with no significant association between cytokine elevation and clearance, leading to a median time to viral clearance of 10 days, consistent with observations in mild human infections. Given these parameter estimates, we predict that a prophylactic treatment blocking 90% of viral production or viral infection could prevent viral growth. In conclusion, our results provide estimates of SARS-CoV-2 viral kinetic parameters in an experimental model of mild infection and they provide means to assess the efficacy of future antiviral treatments.

Identifiants

pubmed: 33730053
doi: 10.1371/journal.pcbi.1008785
pii: PCOMPBIOL-D-20-01686
pmc: PMC8007039
doi:

Substances chimiques

Antiviral Agents 0
Cytokines 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1008785

Déclaration de conflit d'intérêts

I have read the journal’s policy and the authors of this manuscript have the following competing interests: A.G. PhD grant has been provided by ROCHE Company. J.G. has worked as consultant for ROCHE Company.

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Auteurs

Antonio Gonçalves (A)

Université de Paris, IAME, INSERM, Paris, France.

Pauline Maisonnasse (P)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Flora Donati (F)

Unité de Génétique Moléculaire des Virus à ARN, GMVR: Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.
Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.

Mélanie Albert (M)

Unité de Génétique Moléculaire des Virus à ARN, GMVR: Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.
Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.

Sylvie Behillil (S)

Unité de Génétique Moléculaire des Virus à ARN, GMVR: Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.
Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.

Vanessa Contreras (V)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Thibaut Naninck (T)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Romain Marlin (R)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Caroline Solas (C)

Aix-Marseille Univ, APHM, Unité des Virus Emergents (UVE) IRD 190, INSERM 1207, Laboratoire de Pharmacocinétique et Toxicologie, Hôpital La Timone, Marseille, France.

Andres Pizzorno (A)

CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.

Julien Lemaitre (J)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Nidhal Kahlaoui (N)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Olivier Terrier (O)

CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.

Raphael Ho Tsong Fang (R)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Vincent Enouf (V)

Unité de Génétique Moléculaire des Virus à ARN, GMVR: Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.
Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.
Plate-forme de microbiologie mutualisée (P2M), Pasteur International Bioresources Network (PIBnet), Institut Pasteur, Paris, France.

Nathalie Dereuddre-Bosquet (N)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Angela Brisebarre (A)

Unité de Génétique Moléculaire des Virus à ARN, GMVR: Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.
Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.

Franck Touret (F)

Unité des Virus Emergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.

Catherine Chapon (C)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Bruno Hoen (B)

Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France.

Bruno Lina (B)

CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.
Laboratoire de Virologie, Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.

Manuel Rosa Calatrava (M)

CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.

Xavier de Lamballerie (X)

Unité des Virus Emergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.

France Mentré (F)

Université de Paris, IAME, INSERM, Paris, France.

Roger Le Grand (R)

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.

Sylvie van der Werf (S)

Unité de Génétique Moléculaire des Virus à ARN, GMVR: Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.
Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.

Jérémie Guedj (J)

Université de Paris, IAME, INSERM, Paris, France.

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