Innate immune response to respiratory viruses

Doctoral thesis English OPEN
Kar, Satwik
  • Subject: QR180 | R1

The innate immune system has a variety of ways of recognizing infection from pathogens such as viruses and bacteria. One of its first lines of defence is to detect Pattern Associated Molecular Patterns (PAMPs) using Pattern Recognition Receptors (PRRs) such as the Toll-Like Receptors (TLRs), the RIG-Like Helicases (RLHs) and the Nod-Like Receptors (NLRs). These receptors recognize certain molecular structures from the pathogens and lead to first line of defence which includes increased cytokines and IFNs.\ud This study delineate the human body’s innate immune responses to human respiratory viruses such as HRV (Human Rhinovirus), RSV (Respiratory Syncytial Virus) and IAV (Influenza A virus). In Vitro experiments carried out on various kinds of lung tissues suggest that respiratory disease pathogenesis is related to inflammatory mediators including interleukins and cytokines produced by the host’s innate immune system.\ud Virus induced respiratory tract infection are known to trigger bronchiolitis, wheezing and acute asthma exacerbations, as a result of inflammation of lung tissues and excessive release of pro- inflammatory cytokines such as IL-1β. This study identifies that intracellular macromolecular complexes called inflammasomes assemble as a result of viral trigger. Inflammasomes convert the inactive forms of the pro-inflammatory cytokines to their active forms. Although the exact mechanism of activations of these complexes was unknown. This study identified that Virus encoded proteins such as the 2B protein of HRV, the SH protein from RSV and the Influenza M2 which are also termed viroporins can activate the inflammasome by causing ion imbalance (across cells membranes and organelles). Thus providing a trigger for inflammasome assemblage.\ud v\ud Drugs which act as Ion channel blockers have been shown to block viroporin activity and hence reduce IL-1β production. Therefore in the future the use of ion inhibitors could be a possible therapeutic intervention in order to reduce lung inflammation and prevent associated respiratory disease such as COPD and Asthma.
  • References (18)
    18 references, page 1 of 2

    epithelial cells to double-stranded RNA and influenza A virus. J Biol Chem 280: 5571-5580.

    Haeberle HA, Takizawa R, Casola A, Brasier AR, Dieterich HJ, Van Rooijen N, Gatalica Z, Garofalo RP. 2002. Respiratory syncytial virus-induced activation of nuclear factor-kappaB in the lung involves alveolar macrophages and toll-like receptor 4-dependent pathways. J Infect Dis 186: 1199-1206.

    Halasi M, Wang M, Chavan TS, Gaponenko V, Hay N, Gartel AL. 2013. ROS inhibitor N-acetyl-L-cysteine antagonizes the activity of proteasome inhibitors.

    Biochem J 454: 201-208.

    Hall CB. 1999. Respiratory syncytial virus: A continuing culprit and conundrum.

    J Pediatr 135: 2-7.

    Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, Fitzgerald KA, Latz E, Moore KJ, Golenbock DT. 2008. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol 9: 857-865.

    Harada T, Tautz N, Thiel HJ. 2000. E2-p7 region of the bovine viral diarrhea virus polyprotein: processing and functional studies. J Virol 74: 9498-9506.

    Harutyunyan S, Kumar M, Sedivy A, Subirats X, Kowalski H, Kohler G, Blaas D. 2013. Viral uncoating is directional: exit of the genomic RNA in a common cold virus starts with the poly-(A) tail at the 3'-end. PLoS Pathog 9: e1003270.

    Heil,F., Hemmi,H., Hochrein,H., Ampenberger,F., Kirschning,C., Akira,S., Lipford,G., Wagner,H., and Bauer,S. (2004). Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science 303, 1526-1529.

  • Related Research Results (2)
  • Metrics
    0
    views in OpenAIRE
    0
    views in local repository
    83
    downloads in local repository

    The information is available from the following content providers:

    From Number Of Views Number Of Downloads
    Online Research @ Cardiff - IRUS-UK 0 83
Share - Bookmark