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
相关论文
共 50 条
  • [31] Evidence of SARS-CoV-2 infection in pets, captive non-human primates and farm animals in Central Africa
    Maganga, Gael D.
    Ngoubangoye, Barthelemy
    Koumba, Jumafra P.
    Lekana-Douki, Sonia
    Kinga, Ivan C. Moussadji
    Tsoumbou, Thierry A.
    Beyeme, Antoine M. Mbeang
    Mebaley, Telstar G. Ndong
    Lekana-Douki, Jean-Bernard
    ASIAN PACIFIC JOURNAL OF TROPICAL MEDICINE, 2022, 15 (05) : 232 - 235
  • [32] Protein-based SARS-CoV-2 spike vaccine booster increases cross-neutralization against SARS-CoV-2 variants of concern in non-human primates
    Vincent Pavot
    Catherine Berry
    Michael Kishko
    Natalie G. Anosova
    Dean Huang
    Tim Tibbitts
    Alice Raillard
    Sylviane Gautheron
    Cindy Gutzeit
    Marguerite Koutsoukos
    Roman M. Chicz
    Valerie Lecouturier
    Nature Communications, 13
  • [33] Protein-based SARS-CoV-2 spike vaccine booster increases cross-neutralization against SARS-CoV-2 variants of concern in non-human primates
    Pavot, Vincent
    Berry, Catherine
    Kishko, Michael
    Anosova, Natalie G.
    Huang, Dean
    Tibbitts, Tim
    Raillard, Alice
    Gautheron, Sylviane
    Gutzeit, Cindy
    Koutsoukos, Marguerite
    Chicz, Roman M.
    Lecouturier, Valerie
    NATURE COMMUNICATIONS, 2022, 13 (01)
  • [34] Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates
    Fahlberg, M. D.
    Blair, R. V.
    Doyle-Meyers, L. A.
    Midkiff, C. C.
    Zenere, G.
    Russell-Lodrigue, K. E.
    Monjure, C. J.
    Haupt, E. H.
    Penney, T. P.
    Lehmicke, G.
    Threeton, B. M.
    Golden, N.
    Datta, P. K.
    Roy, C. J.
    Bohm, R. P.
    Maness, N. J.
    Fischer, T.
    Rappaport, J.
    Vaccari, M.
    NATURE COMMUNICATIONS, 2020, 11 (01)
  • [35] Preclinical evaluation of PHH-1V vaccine candidate against SARS-CoV-2 in non-human primates
    Prenafeta, Antoni
    Bech-Sabat, Gregori
    Moros, Alexandra
    Barreiro, Antonio
    Fernandez, Alex
    Canete, Manuel
    Roca, Merce
    Gonzalez-Gonzalez, Luis
    Garriga, Carme
    Confais, Joachim
    Toussenot, Marion
    Contamin, Hugues
    Pizzorno, Andres
    Rosa-Calatrava, Manuel
    Pradenas, Edwards
    Marfil, Silvia
    Blanco, Julia
    Rica, Paula Cebollada
    Sistere-Oro, Marta
    Meyerhans, Andreas
    Lorca, Cristina
    Segales, Joaquim
    Prat, Teresa
    March, Ricard
    Ferrer, Laura
    ISCIENCE, 2023, 26 (07)
  • [36] Proteomic analysis of lung responses to SARS-CoV-2 infection in aged non-human primates: clinical and research relevance
    Garcia-Vilanova, Andreu
    Allue-Guardia, Anna
    Chacon, Nadine M.
    Akhter, Anwari
    Singh, Dhiraj Kumar
    Kaushal, Deepak
    Restrepo, Blanca I.
    Schlesinger, Larry S.
    Turner, Joanne
    Weintraub, Susan T.
    Torrelles, Jordi B.
    GEROSCIENCE, 2024, : 6395 - 6417
  • [37] Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates
    M. D. Fahlberg
    R. V. Blair
    L. A. Doyle-Meyers
    C. C. Midkiff
    G. Zenere
    K. E. Russell-Lodrigue
    C. J. Monjure
    E. H. Haupt
    T. P. Penney
    G. Lehmicke
    B. M. Threeton
    N. Golden
    P. K. Datta
    C. J. Roy
    R. P. Bohm
    N. J. Maness
    T. Fischer
    J. Rappaport
    M. Vaccari
    Nature Communications, 11
  • [38] SARS-CoV-2 surveillance for a non-human primate breeding research facility
    Yee, JoAnn L.
    Van Rompay, Koen K. A.
    Carpenter, Amanda B.
    Nham, Peter B.
    Halley, Bryson M.
    Iyer, Smita S.
    Hartigan-O'Connor, Dennis J.
    Miller, Christopher J.
    Roberts, Jeffrey A.
    JOURNAL OF MEDICAL PRIMATOLOGY, 2020, 49 (06) : 322 - 331
  • [39] Viral dynamics of SARS-CoV-2 in immunocompromised patients
    Utzon, Andrea N.
    Johansen, Isik S.
    Bang, Line L.
    Pedersen, Rune M.
    Andersen, Thomas E.
    Madsen, Lone W.
    CLINICAL MICROBIOLOGY AND INFECTION, 2023, 29 (08) : 1087.e1 - 1087.e3
  • [40] SARS-CoV-2 viral dynamics in immunocompromised patients
    Caillard, Sophie
    Benotmane, Ilies
    Gautier Vargas, Gabriela
    Perrin, Peggy
    Fafi-Kremer, Samira
    AMERICAN JOURNAL OF TRANSPLANTATION, 2021, 21 (04) : 1667 - 1669