Dealnorth0995

ue in that it elicits predominantly non-neutralizing antibodies that activate Fc receptors and bind complement, and a glycoprotein D subunit vaccine that elicits neutralizing, but not Fc receptor activating or complement binding responses. Only the single-cycle vaccine provided both active and passive protection against a lethal ocular challenge. These findings greatly expand our understanding of the types of immune responses needed to protect the eye and will inform future prophylactic and therapeutic strategies. Copyright © 2020 American Society for Microbiology.Respiratory syncytial virus (RSV) is a major cause of paediatric respiratory disease. Large numbers of neutrophils are recruited into the airways of children with severe RSV disease. It is not clear whether or how neutrophils enhance recovery from disease or contribute to its pathology.Using an in vitro model of the differentiated airway epithelium, we found that addition of physiological concentrations of neutrophils to RSV infected nasal cultures was associated with greater epithelial damage with lower ciliary activity, cilia loss, less tight junction expression (ZO-1) and more detachment of epithelial cells than seen with RSV infection alone. This was also associated with a decrease in infectious virus and fewer RSV positive cells in cultures after neutrophil exposure compared to pre-exposure. Epithelial damage in response to RSV infection was associated with neutrophil activation (within 1h), and neutrophil degranulation with significantly greater cellular expression of CD11b, MPO and higher neutrophil elastase and myeloperoxidase activity in apical surface medias compared to that from mock-infected AECs. We also recovered more apoptotic neutrophils from RSV infected cultures (>40%), compared to less then 5% in mock infected cultures after 4h.The results of this study could provide important insights into the role of neutrophils in host response in the airway.Importance This study shows that the RSV infected human airway drives changes in the behaviour of human neutrophils including increasing activation markers and delaying apoptosis that results in greater airway damage and viral clearance. Copyright © 2020 Deng et al.Virus infection leads to activation of the interferon-induced endoribonuclease, RNase L, which results in degradation of viral and cellular RNAs. Both cellular and viral RNA cleavage products of RNase L bind pattern recognition receptors (PRR) like Retinoic acid-inducible I (Rig-I) and or melanoma differentiation-associated protein 5 (MDA5) to further amplify interferon (IFN) production and antiviral response. Although much is known about the mechanics of ligand binding and PRR activation, how the cells coordinate RNA sensing to signaling response and interferon production remains unclear. We show that RNA cleavage products of RNase L activity induce formation of antiviral stress granule (avSG) by regulating activation of double-stranded RNA (dsRNA)-dependent protein kinase R (PKR), and recruit antiviral proteins Rig-I, PKR, OAS and RNase L to avSG. Biochemical analysis of purified avSG showed interaction of key stress granule protein, G3BP1, with only PKR and Rig-I and not with OAS or RNase L. AvSG assembly N production. This study identifies a novel role of antiviral stress granules induced by RNase L as an antiviral signaling hub to coordinate the RNA ligands with cognate receptors to mount effective host response during viral infections. Copyright © 2020 Manivannan et al.During the replication of parainfluenza virus type 5 (PIV5) copyback defective virus genomes (DVGs) are erroneously produced and are packaged into "infectious" virus particles. Inflammation inhibitor Copyback DVGs are primary inducers of innate intracellular responses, including the interferon (IFN) response. Whilst DVGs can interfere with the replication of non-defective (ND) virus genomes and activate the IFN-induction cascade before ND PIV5 can block the production of IFN, we demonstrate that the converse is also true, i.e. high levels of ND virus can block the ability of DVGs to activate the IFN-induction cascade. By following the replication and amplification of DVGs in A549 cells that are deficient in a variety of innate intracellular antiviral responses, we show that DVGs induce an uncharacterised IFN-independent innate response(s) that limits their replication. High throughput sequencing was used to characterise the molecular structure of copyback DVGs. Whilst there appears to be no sequence-specific break or rejoining poins, genome region, size and structural preferences are selected for during their evolution and amplification. Copyright © 2020 Wignall-Fleming et al.Influenza A virus encodes a viral RNA-dependent RNA polymerase (FluPolA), which is responsible for transcribing and replicating the negative-sense viral RNA (vRNA) genome. FluPolA transcribes vRNA using a host capped mRNA primer, and replicates it by synthesising a positive-sense complementary RNA (cRNA) intermediate which is copied back into vRNA. To carry out these functions, FluPolA interacts with vRNA and cRNA using conserved promoter elements at the 5' and 3' termini. Recent structural studies have identified a new surface binding site for the 3' vRNA and cRNA promoters on FluPolA, referred to as the Mode B site. However, the role of this binding site in FluPolA function is unknown. In this study we used a combination of cell-based and biochemical assays to show that the Mode B site is important for both viral genome transcription and replication. Furthermore, we show that the Mode B site is not needed for initiating transcription in vitro but is required to synthesise a full-length product. This is consnome transcription by the influenza virus polymerase, and may be applicable to other related viruses. Copyright © 2020 American Society for Microbiology.Echovirus 30 (E30), a member of the enterovirus B species, is a major cause of viral meningitis, targeting children and adults alike. While it is a frequently isolated enterovirus and the cause of several outbreaks all over the world, suprisingly little is known regarding its entry and replication strategy within cells. In this study, we used E30 Bastianni (E30B) generated from an infectious cDNA clone in order to study early entry events during infection in human RD cells. E30B required the newly discovered Fc echovirus receptor (FcRn) for succesful infection, but not the Coxsackievirus and Adenovirus Receptor (CAR) or Decay-Accelerating Factor (DAF), although an interaction with DAF was observed. Double-stranded RNA replication intermediate was generated between 2 and 3 h post-infection (p.i.). and viral capsid production was initiated between 4 and 5 h p.i. The drugs affecting Rac1 (NSC 23766) and cholesterol (Filipin III) compromised infection, whereas bafilomycin A1, dyngo, U-73122, wortmannin and nocodazole did not, suggesting the virus follows an enterovirus-triggered macropinocytic pathway rather than the clathrin pathway.