Étude de l'infection par le métapneumovirus humain : facteurs de virulence et développement de vaccins vivants atténués

Abstract : Human metapneumovirus (hMPV) is a major pathogen responsible of acute respiratory tract infections, such as bronchiolitis or pneumonia, affecting especially infants, under five years old, elderly individuals and immunocompromised adults. Identified since 2001, this virus and its pathogenesis still remain largely unknown and no licensed vaccines or specific antivirals against hMPV are currently available. In this context, my research project was built over two main subjects: (i) The study of the fusion F glycoprotein which is the major antigenic protein of hMPV and is responsible of viral entry into host cell. By its crucial role for the virus, the F protein has already been characterized in several structural and/or functional studies. Thus, it has been described that the hMPV F protein induces membrane fusion autonomously, resulting in variable cytopathic effects in vitro, in a strain-dependent manner. However, as the determinants of the hMPV fusogenic activity are not well characterized yet, we focused on identification of some of these, located in heptad repeats domains of the protein. (ii) The evaluation of hMPV SH and G gene deletion for viral attenuation. Liveattenuated hMPV vaccine candidates for infants’ immunization has been constructed thank to this deletion approach at the beginning of hMPV vaccine development efforts. Despite encouraging results, these candidates have not been further characterized and the importance of the viral background has not been evaluated
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Julia Dubois. Étude de l'infection par le métapneumovirus humain : facteurs de virulence et développement de vaccins vivants atténués. Biologie cellulaire. Université de Lyon; Université Laval (Québec, Canada), 2018. Français. ⟨NNT : 2018LYSE1018⟩. ⟨tel-02291065v2⟩

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