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

被引:31
|
作者
Goncalves, Antonio [1 ]
Maisonnasse, Pauline [2 ,3 ]
Donati, Flora [4 ,5 ]
Albert, Melanie [4 ,5 ]
Behillil, Sylvie [4 ,5 ]
Contreras, Vanessa [2 ,3 ]
Naninck, Thibaut [2 ,3 ]
Marlin, Romain [2 ,3 ]
Solas, Caroline [6 ]
Pizzorno, Andres [7 ]
Lemaitre, Julien [2 ,3 ]
Kahlaoui, Nidhal [2 ,3 ]
Terrier, Olivier [7 ]
Fang, Raphael Ho Tsong [2 ,3 ]
Enouf, Vincent [4 ,5 ,8 ]
Dereuddre-Bosquet, Nathalie [2 ,3 ]
Brisebarre, Angela [4 ,5 ]
Touret, Franck [9 ]
Chapon, Catherine [2 ,3 ]
Hoen, Bruno [10 ]
Lina, Bruno [7 ,11 ]
Calatrava, Manuel Rosa [7 ]
de Lamballerie, Xavier [9 ]
Mentre, France [1 ]
Le Grand, Roger [2 ,3 ]
van der Werf, Sylvie [4 ,5 ]
Guedj, Jeremie [1 ]
机构
[1] Univ Paris, INSERM, IAME, Paris, France
[2] Univ Paris Saclay, Ctr Immunol Viral Autoimmune Hematol & Bacterial, CEA, INSERM, Fontenay Aux Roses, France
[3] Univ Paris Saclay, Ctr Immunol Viral Autoimmune Hematol & Bacterial, CEA, INSERM, Le Kremlin Bicetre, France
[4] Univ Paris, GMVR Inst Pasteur, Unite Genet Mol Virus ARN, UMR CNRS 3569, Paris, France
[5] Inst Pasteur, Ctr Natl Reference Virus Infect Resp Dont Grippe, Paris, France
[6] Aix Marseille Univ, Hop La Timone, AP HM,Lab Pharmacocinet & Toxicol, Unite Virus Emergents UVE IRD 190,INSERM 1207, Marseille, France
[7] Univ Claude Bernard Lyon 1, Univ Lyon, Ctr Int Rech Infectiol, CIRI,ENS Lyon,Team VirPath,Inserm U1111,CNRS,UMR5, Lyon, France
[8] Inst Pasteur, Pasteur Int Bioresources Network PIBnet, Plate Forme Microbiol Mutualisee P2M, Paris, France
[9] UVE Aix Marseille Univ, Unite Virus Emergents, IHU Mediterranee Infect, IRD 190,INSERM 1207, Marseille, France
[10] Inst Pasteur, Emerging Dis Epidemiol Unit, Paris, France
[11] Hosp Civils Lyon, Grp Hosp Nord, Ctr Natl Reference Virus Infect Resp Dont Grippe, Inst Agents Infect,Lab Virol, Lyon, France
基金
比尔及梅琳达.盖茨基金会;
关键词
PROVIDES INSIGHTS; INFECTION; MODEL;
D O I
10.1371/journal.pcbi.1008785
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Author summary Non-human primates infected with SARS-CoV-2 develop a mild infection resembling asymptomatic human infection. Here we used viral dynamic modelling to characterize the nasopharyngeal and tracheal viral loads. We found that viral load rapidly declined after peak viral load despite the absence of association between model parameters and immune markers. The within-host reproductive basic reproduction number was approximately equal to 6 and 4 in nasopharynx and trachea suggesting that a prophylactic therapy blocking viral entry or production with 90% efficacy could be sufficient to prevent viral growth and peak viral load. 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 (>10(4) 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.
引用
收藏
页数:15
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