Targeting host calpain proteases decreases influenza A virus infection.

Influenza A viruses (IAV) trigger contagious acute respiratory diseases. A better understanding of the molecular mechanisms of IAV pathogenesis and host immune responses is required for the development of more efficient treatments of severe influenza. Calpains are intracellular proteases that participate in diverse cellular responses, including inflammation.

Multiple hosts and Influenza A viruses genetic mixing.

Influenza A viruses have a segmented, negative-stranded RNA genome. These viruses are classified according to the antigenic properties of the two glycoproteins, expressed on the surface of the virus particles, the hemagglutinin (HA or H) and the neuraminidase (NA or N). To date, 17 H and 10 N have been described and 116 HxNy combinations or subtypes reported.

Interactions moléculaires entre les ribonucléoprotéines des virus influenza de type A et la cellule hôte.

The study of molecular interactions between viral components and cellular components have become a very active field of research during the recent years. At stake is a better understanding of the determinants of viral pathogenicity and zoonotic potential, and the identification of new therapeutic targets. The viral ribonucleoproteins (vRNPs), which are key components of the viral multiplication cycle and relatively conserved, are of particular interest.

Influenza A virus progeny vRNP trafficking in live infected cells studied with the virus-encoded fluorescently tagged PB2 protein.

Dynamic studies of influenza virus infection in the live cells are limited because of the lack of appropriate methods for non-invasive detection of the viral components. Using the split-GFP strategy, we have recently developed and characterized an unimpaired recombinant influenza A virus encoding a tagged PB2 subunit of RNA-dependent RNA polymerase, which enabled continuous real-time visualization of the viral ribonucleoproteins (vRNPs) in living cells (Avilov, Moisy, Munier, Schraidt, Naffakh and Cusack [12]). Here, using this virus, we studied vRNP trafficking and interaction with Rab11 in the context of quasi-wild type infection.

HMGB1 protein binds to influenza virus nucleoprotein and promotes viral replication.

Influenza virus has evolved replication strategies that hijack host cell pathways. To uncover interactions between viral macromolecules and host proteins, we applied a phage display strategy. A library of human cDNA expression products displayed on filamentous phages was submitted to affinity selection for influenza viral ribonucleoproteins (vRNPs).

Replication-competent influenza A virus that encodes a split-green fluorescent protein-tagged PB2 polymerase subunit allows live-cell imaging of the virus life cycle.

Studies on the intracellular trafficking of influenza virus ribonucleoproteins are currently limited by the lack of a method enabling their visualization during infection in single cells. This is largely due to the difficulty of encoding fluorescent fusion proteins within the viral genome. To circumvent this limitation, we used the split-green fluorescent protein (split-GFP) system (S.