Instituto Gulbenkian de Ciência

PhD Thesis Defense Nuno Filipe Brito Pais Dos Santos 02/06/2021 15:00 Zoom
Speaker: Nuno Filipe Brito Pais Dos Santos
Host: PGCD2016 and Maria João Amorim
Title: Interplay between DAF and viral proteins HA and NA modulates viral pathogenesis
Fellowship from the Institute Gulbenkian de Ciência

Jury President: - Dr. Mariana Pinho, Professora Associada do Instituto de Tecnologia Química e Biológica da Universidade Nova de Lisboa, por delegação;
Members of the Jury:
- Dr. Margarida Saraiva, I3S, Porto, Portugal – main jury member;
- Dr. Edward Hutchinson, University of Glasgow, UK – main jury member;
- Dr. Colin Adrain, Queens's University Belfast, UK – jury member;
- Dr. Helena Soares, CEDOC, Portugal – jury member;
- Dr. Maria João Amorim, IGC, Portugal – supervisor.

Abstract:
Host and viral factors contribute to define viral pathology. In this work, we explore the role of complement decay-accelerating factor (DAF) in activating complement and in modulating influenza A virus (IAV) infection via an interplay with the antigenic viral proteins hemagglutinin (HA) and neuraminidase (NA). We observed that DAF, contrary to what could be expected, potentiates complement activation upon IAV infection. Particularly, we describe that the viral sialidase NA acts on DAF, in a strain-specific manner, removing ?-2,6-linked sialic acids and propose that this may regulate pathogenicity. Given that the recognition of different conformations of sialic acid by the virus is a key driver in IAV intra- and interspecies transmission, our findings may have implications for zoonotic events.
Our results also showed that besides DAF increasing complement activation, it exacerbates immune cell recruitment, especially of neutrophils and monocytes, which promote lung immunopathology without altering viral loads. Therefore, DAF reveals a novel mechanism of virulence in infection.
Additionally, we show an alternative mechanism of controlling pathology, based on a mutation in viral HA that attenuates the virus. We observed that this mutation prevented viral replication and penetration in the lung tissue, conferring protection associated with decreased viral
loads.
Taken together, our results add to the understanding of how host and viral factors may contribute in distinct ways to viral-mediated pathology.