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Abstract: The genome of influenza A viruses is comprised of eight negative-sense viral RNAs (vRNAs) that form viral ribonucleoproteins (vRNPs). In order to be infectious, an influenza A viral particle must encapsidate at least one copy of each of the vRNAs. Thus, even though genome segmentation is evolutionary advantageous, it undeniably complicates viral assembly, which is believed to occur through a selective mechanism that still remains to be understood. Using electron tomography 3D-reconstructions, we show that the eight vRNPs of an influenza A Moscow/10/99 (H3N2) virus are interconnected within a star-like structure as they emerge from a unique “transition zone” at the budding tip of the virions. Notably, this “transition zone” is thick enough to accommodate all described packaging signals. We also report that, in vitro, each vRNA segment is involved in a direct contact with at least one other vRNA partner, in a single network of intermolecular interactions. We show that in several cases, the regions involved in vRNA/vRNA interactions overlap with previously identified packaging signals. Our results thus provide support for the involvement of RNA/RNA interactions in the selection and specific packaging of influenza A genomic RNAs, which appear embedded into an organised supramolecular complex likely held together by direct base-pairings between packaging signals. [Copyright &y& Elsevier]

Abstract: Influenza is one of the most common infectious diseases in humans occurring as seasonal epidemic and sporadic pandemic outbreaks. The ongoing infections of humans with avian H5N1 influenza A viruses (IAV) and the past 2009 pandemic caused by the quadruple human/avian/swine reassortant (H1N1) virus highlights the permanent threat caused by these viruses. This review aims to describe the interaction between the virus and the host, with a particular focus on the role of proteases and HLA-G in the pathogenicity of influenza viruses. [Copyright &y& Elsevier]

Background: Evidence has recently emerged indicating that in addition to large airborne droplets, fine aerosol particles can be an important mode of influenza transmission that may have been hitherto underestimated. Furthermore, recent performance studies evaluating airborne infection isolation (AII) rooms designed to house infectious patients have revealed major discrepancies between what is prescribed and what is actually measured. Methods: We conducted an experimental study to investigate the use of high-throughput in-room air decontamination units for supplemental protection against airborne contamination in areas that host infectious patients. The study included both intrinsic performance tests of the air-decontamination unit against biological aerosols of particular epidemiologic interest and field tests in a hospital AII room under different ventilation scenarios. Results: The unit tested efficiently eradicated airborne H5N2 influenza and Mycobacterium bovis (a 4- to 5-log single-pass reduction) and, when implemented with a room extractor, reduced the peak contamination levels by a factor of 5, with decontamination rates at least 33% faster than those achieved with the extractor alone. Conclusion: High-throughput in-room air treatment units can provide supplemental control of airborne pathogen levels in patient isolation rooms. [Copyright &y& Elsevier]

Influenza A viruses package their segmented RNA genome in a selective manner. Electron tomography, biochemical assays, and replication assays of viruses produced by reverse genetics recently unveiled molecular details of this mechanism, whereby different influenza viral strains form different and unique networks of direct intermolecular RNA-RNA interactions. Together with detailed views of the three-dimensional structure of the viral ribonucleoparticles, these recent advances help us understand the rules that govern genome packaging. They also have deep implications for the genetic reassortment processes, which are responsible for devastating pandemics. [ABSTRACT FROM AUTHOR]

Abstract: We have previously shown a clear differential genetic evolution of the hemagglutinin (HA) of human AH1N1 and AH1N2 viruses, isolated in southern France between 2001 and 2004. However, our analysis revealed that one single AH1N2 isolate, detected in 2003 (A/Lyon/0838/2003), had its HA clustering within the HAs of the AH1N1 subtypes. To determine if this virus was a new reassortant, the nucleotide sequences of its eight RNA gene segments were compared with those of five representative strains of the AH1N1, AH1N2 and AH3N2 viruses, isolated during the same time-period. According to the sequences obtained, the neuraminidase (NA) gene segment of the A/Lyon/0838/2003 (H1N2) virus was genetically closely related to those of the AH1N2 viruses, whereas the six internal genes appeared to be clustering with those of the AH1N1 viruses. This suggested that the A/Lyon/0838/2003 (H1N2) virus was the result of a second reassortment event that had occurred during the winter of 2002–2003; the N2 gene segment of an AH1N2 virus being introduced into an AH1N1 genetic background. Subsequently, we analysed the extremities of each gene segment of the viruses from the different subtypes, and experimentally reproduced, in vitro, AH1N2 reassortant viruses through co-infection of Madin–Darby canine kidney (MDCK) cells with both AH1N1 and AH1N2 viruses, isolated in the 2002–2003 influenza season. While the comparison of the AH1N1 and the AH1N2 gene segment extremities revealed no major differences, we successfully reproduced an AH1N2 reassortant virus similar to the A/Lyon/0838/2003 (H1N2) virus. This result provided an experimental evidence of the compatibility between their respective surface H1 and N2 glycoproteins, and suggests that similar events may occur silently amongst human subtypes. [Copyright &y& Elsevier]

Abstract: The knowledge of parainfluenza type 5 (PIV-5) virion morphology is essentially based on the observation of negatively stained preparations in conventional transmission electron microscopy (CTEM). In this study, the ultrastructure of frozen-hydrated intact PIV-5 was examined by cryo-electron microscopy (cryo-EM). Cryo-EM revealed a majority of spherical virions (70%), with a lower pleiomorphy than originally observed in CTEM. Phospholipid bilayer thickness, spike length and glycoprotein spikes density were measured. About 2000 glycoprotein spikes were present in an average-sized spherical virion. Altogether, these data depict a more precise view of PIV-5 morphology. [Copyright &y& Elsevier]