title: Pseudotyping Serotype 5 Adenovirus with the Fiber from Other Serotypes Uncovers a Key Role of the Fiber Protein in Adenovirus 5-Induced Thrombocytopenia.
abstract: Adenovirus (Ad) infection in humans is associated with inflammatory responses and thrombocytopenia. Although several studies were conducted in mice models to understand molecular and cellular mechanisms of Ad-induced inflammatory responses, only few of them turned their interest toward the mechanisms of Ad-induced thrombocytopenia. Using different depletion methods, the present study ruled out any significant role of spleen, macrophages, and vitamin K-dependent factor in Ad-induced thrombocytopenia. Interestingly, mice displaying thrombocytopenia expressed high levels of cytokines/chemokines after Ad administration. Most importantly, pseudotyping adenovirus with the fiber protein from other serotypes was associated with reduction of both cytokine/chemokine production and thrombocytopenia. Altogether, our results suggest that capsid fiber protein (and more precisely its shaft) of Ad serotype 5 triggers the cytokine production that leads to Ad-induced thrombocytopenia.
authors.affiliation: 1 UMR 8203 Vectorologie et Thérapeutiques Anticancéreuses, CNRS, Univ. Paris-Sud , Gustave Roussy, Universite Paris-Saclay, Villejuif, France .
authors.forename: Najat
authors.initials: N
authors.lastname: Raddi
authors.affiliation: 1 UMR 8203 Vectorologie et Thérapeutiques Anticancéreuses, CNRS, Univ. Paris-Sud , Gustave Roussy, Universite Paris-Saclay, Villejuif, France .
authors.forename: Frédéric
authors.initials: F
authors.lastname: Vigant
authors.affiliation: 2 Inserm, U1009, Université Paris-Sud11 , Villejuif, France .|3 Assistance Publique des Hôpitaux de Paris, Laboratoire d'Hématologie, Université Paris-Est Créteil , Hôpital Henri Mondor, Créteil, France .
authors.forename: Oriane
authors.initials: O
authors.lastname: Wagner-Ballon
authors.affiliation: 2 Inserm, U1009, Université Paris-Sud11 , Villejuif, France .|3 Assistance Publique des Hôpitaux de Paris, Laboratoire d'Hématologie, Université Paris-Est Créteil , Hôpital Henri Mondor, Créteil, France .
authors.forename: Stéphane
authors.initials: S
authors.lastname: Giraudier
authors.affiliation: 4 Viral Vaccine Discovery and Early Development, Crucell Holland BV, Leiden, The Netherlands .
authors.forename: Jerome
authors.initials: J
authors.lastname: Custers
authors.affiliation: 5 Institute of Molecular Life Sciences, University of Zurich , Zurich, Switzerland .
authors.forename: Silvio
authors.initials: S
authors.lastname: Hemmi
authors.affiliation: 1 UMR 8203 Vectorologie et Thérapeutiques Anticancéreuses, CNRS, Univ. Paris-Sud , Gustave Roussy, Universite Paris-Saclay, Villejuif, France .
authors.forename: Karim
authors.initials: K
authors.lastname: Benihoud
mesh_terms: D000257:Adenoviridae Infections / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000821:virology*; D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000819:agonists / Q000096:biosynthesis / Q000276:immunology; D005170:Factor X / Q000276:immunology; D005260:Female; D015870:Gene Expression; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D065288:Serogroup; D013154:Spleen / Q000276:immunology / Q000821:virology; D013921:Thrombocytopenia / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000821:virology*
chemical_list: D036022:Capsid Proteins; D016207:Cytokines; C018315:hexon capsid protein, Adenovirus; D005170:Factor X