scholarly journals Replication of Influenza A Virus in Secondary Lymphatic Tissue Contributes to Innate Immune Activation

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 622
Author(s):  
Sarah-Kim Friedrich ◽  
Rosa Schmitz ◽  
Michael Bergerhausen ◽  
Judith Lang ◽  
Vikas Duhan ◽  
...  
Keyword(s):  
Immune System ◽  
Influenza A Virus ◽  
Immune Activation ◽  
Influenza A ◽  
Lymphoid Organs ◽  
Innate Immune ◽  
Intravenous Route ◽  
Lymphatic Tissue ◽  
Innate Immune Activation ◽  
Secondary Lymphoid Organs

The replication of viruses in secondary lymphoid organs guarantees sufficient amounts of pattern-recognition receptor ligands and antigens to activate the innate and adaptive immune system. Viruses with broad cell tropism usually replicate in lymphoid organs; however, whether a virus with a narrow tropism relies on replication in the secondary lymphoid organs to activate the immune system remains not well studied. In this study, we used the artificial intravenous route of infection to determine whether Influenza A virus (IAV) replication can occur in secondary lymphatic organs (SLO) and whether such replication correlates with innate immune activation. Indeed, we found that IAV replicates in secondary lymphatic tissue. IAV replication was dependent on the expression of Sialic acid residues in antigen-presenting cells and on the expression of the interferon-inhibitor UBP43 (Usp18). The replication of IAV correlated with innate immune activation, resulting in IAV eradication. The genetic deletion of Usp18 curbed IAV replication and limited innate immune activation. In conclusion, we found that IAV replicates in SLO, a mechanism which allows innate immune activation.

scholarly journals The influenza virus RNA polymerase as an innate immune agonist and antagonist

2021 ◽  
Author(s):  
Elizaveta Elshina ◽  
Aartjan J. W. te Velthuis
Keyword(s):  
Rna Polymerase ◽  
Influenza A Virus ◽  
Immune Activation ◽  
Influenza A ◽  
Innate Immune ◽  
Lung Damage ◽  
Influenza A Viruses ◽  
Comprehensive Overview ◽  
Innate Immune Activation ◽  
Virus Rna

AbstractInfluenza A viruses cause a mild-to-severe respiratory disease that affects millions of people each year. One of the many determinants of disease outcome is the innate immune response to the viral infection. While antiviral responses are essential for viral clearance, excessive innate immune activation promotes lung damage and disease. The influenza A virus RNA polymerase is one of viral proteins that affect innate immune activation during infection, but the mechanisms behind this activity are not well understood. In this review, we discuss how the viral RNA polymerase can both activate and suppress innate immune responses by either producing immunostimulatory RNA species or directly targeting the components of the innate immune signalling pathway, respectively. Furthermore, we provide a comprehensive overview of the polymerase residues, and their mutations, associated with changes in innate immune activation, and discuss their putative effects on polymerase function based on recent advances in our understanding of the influenza A virus RNA polymerase structure.

scholarly journals Location, Location, Location: Is Membrane Partitioning Everything When It Comes to Innate Immune Activation?

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Martha Triantafilou ◽  
Philipp M. Lepper ◽  
Robin Olden ◽  
Ivo de Seabra Rodrigues Dias ◽  
Kathy Triantafilou
Keyword(s):  
Plasma Membrane ◽  
Immune System ◽  
Lipid Rafts ◽  
Immune Activation ◽  
Innate Immune System ◽  
Innate Immune ◽  
Membrane Microdomains ◽  
General View ◽  
Immune Recognition ◽  
Innate Immune Activation

In the last twenty years, the general view of the plasma membrane has changed from a homogeneous arrangement of lipids to a mosaic of microdomains. It is currently thought that islands of highly ordered saturated lipids and cholesterol, which are laterally mobile, exist in the plane of the plasma membrane. Lipid rafts are thought to provide a means to explain the spatial segregation of certain signalling pathways emanating from the cell surface. They seem to provide the necessary microenvironment in order for certain specialised signalling events to take place, such as the innate immune recognition. The innate immune system seems to employ germ-lined encoded receptors, called pattern recognition receptors (PRRs), in order to detect pathogens. One family of such receptors are the Toll-like receptors (TLRs), which are the central “sensing” apparatus of the innate immune system. In recent years, it has become apparent that TLRs are recruited into membrane microdomains in response to ligands. These nanoscale assemblies of sphingolipid, cholesterol, and TLRs stabilize and coalesce, forming signalling platforms, which transduce signals that lead to innate immune activation. In the current paper, we will investigate all past and current literature concerning recruitment of extracellular and intracellular TLRs into lipid rafts and how this membrane organization modulates innate immune responses.

scholarly journals RNA-based vaccines and innate immune activation: Not too hot and not too cold

2021 ◽  
Vol 29 (4) ◽  
pp. 1365-1366
Author(s):  
Robert Frederickson ◽  
Roland W. Herzog
Keyword(s):  
Immune Activation ◽  
Innate Immune ◽  
Innate Immune Activation
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