Summary of ebolavirus protein roles.

<p>Summary of ebolavirus protein roles.</p

Multiple roles of VP35 during virus replication.

<p>VP35 inhibits the type-I IFN response through several different mechanisms. VP35 can bind to dsRNA, preventing the activation of RIG-I signalling. In addition, VP35 blockade of IRF3 and IRF7 phosphorylation inhibits the production of IFN-β. Recent studies have also highlighted the importance of VP35 in regulating NP–RNA association. During viral genome replication, the VP35 N-terminal peptide binds to NP, enabling the vRNA to associate with the RdRp complex for replication. During virus assembly, VP35 disassociates, enabling NP to oligomerise, bind RNA, and form the nucleocapsid. 5’PPP, 5’ triphosphate; dsRNA, double-stranded RNA; IFN, interferon; IKK, inhibitor of nuclear factor kappa B kinase subunit epsilon; IRF, interferon regulatory factor; MAVS, mitochondrial antiviral-signalling protein; MDA5, melanoma differentiation-associated protein 5; NP, nucleoprotein; PACT, protein activator of the interferon-induced protein kinase; RdRp, RNA-dependent RNA polymerase; RIG-I, retinoic acid-inducible gene I; TANK, tumour necrosis factor–receptor-associated factor family member–associated nuclear factor kappa B activator; TBK1, tumour necrosis factor–receptor-associated factor family member–associated nuclear factor kappa B activator binding kinase 1; TRAF3, tumour necrosis factor–receptor-associated factor 3; VP, viral protein; vRNA, viral RNA.</p

Ebolavirus proteins VP30, VP35, and VP40 are suppressors of RNA silencing.

<p>Cellular RNA interference requires the assembly of the Dicer:TRBP:PACT complex. VP30 inhibits RNAi by interacting with Dicer, preventing TRBP binding and complex activity. VP35 also inhibits complex assembly by binding TRBP and PACT, preventing their association with Dicer. VP40 suppresses RNAi during infection or when transferred to bystander immune cells through exosomes, though the mechanism by which VP40 inhibits the Dicer machinery is currently unknown. PACT, protein activator of the interferon-induced protein kinase; RNAi, RNA interference; TRBP, <i>Trans</i>-activation response RNA binding protein; VP, viral protein.</p

Publisher Correction: SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway (Nature Microbiology, (2022), 7, 8, (1161-1179), 10.1038/s41564-022-01143-7)

In the version of this article initially published, the author affiliation information was incomplete, neglecting to note that Brian J. Willett, Joe Grove, Oscar A. MacLean, Craig Wilkie, Giuditta De Lorenzo, Wilhelm Furnon, Diego Cantoni, Sam Scott, Nicola Logan and Shirin Ashraf contributed equally and that John Haughney, David L. Robertson, Massimo Palmarini, Surajit Ray and Emma C. Thomson jointly supervised the work, as now indicated in the HTML and PDF versions of the article

DataSheet_1_Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysis.pdf

The role of the mucosal pulmonary antibody response in coronavirus disease 2019 (COVID-19) outcome remains unclear. Here, we found that in bronchoalveolar lavage (BAL) samples from 48 patients with severe COVID-19-infected with the ancestral Wuhan virus, mucosal IgG and IgA specific for S1, receptor-binding domain (RBD), S2, and nucleocapsid protein (NP) emerged in BAL containing viruses early in infection and persist after virus elimination, with more IgA than IgG for all antigens tested. Furthermore, spike-IgA and spike-IgG immune complexes were detected in BAL, especially when the lung virus has been cleared. BAL IgG and IgA recognized the four main RBD variants. BAL neutralizing titers were higher early in COVID-19 when virus replicates in the lung than later in infection after viral clearance. Patients with fatal COVID-19, in contrast to survivors, developed higher levels of mucosal spike-specific IgA than IgG but lost neutralizing activities over time and had reduced IL-1β in the lung. Altogether, mucosal spike and NP-specific IgG and S1-specific IgA persisting after lung severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance and low pulmonary IL-1β correlate with COVID-19 fatal outcome. Thus, mucosal SARS-CoV-2-specific antibodies may have adverse functions in addition to protective neutralization.HighlightsMucosal pulmonary antibody response in COVID-19 outcome remains unclear. We show that in severe COVID-19 patients, mucosal pulmonary non-neutralizing SARS-CoV-2 IgA persit after viral clearance in the lung. Furthermore, low lung IL-1β correlate with fatal COVID-19. Altogether, mucosal IgA may exert harmful functions beside protective neutralization.</p