IRF5 geeni .IRF5 on avainasemassa Covid-19 hyperinflammaatiossa. Hexosaminitie säätyy ylös viruksen replikaation eduksi. Calmette-rokotuksen osuus.

Entrez Gene Summary for IRF5 Gene /(7q321)

• This gene encodes a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats. Alternative promoter use and alternative splicing result in multiple transcript variants, and a 30-nt indel polymorphism (SNP rs60344245) can result in loss of a 10-aa segment. [provided by RefSeq, Dec 2016]

GeneCards Summary for IRF5 Gene

IRF5 (Interferon Regulatory Factor 5) is a Protein Coding gene. Diseases associated with IRF5 include Systemic Lupus Erythematosus 10 and Inflammatory Bowel Disease 14. Among its related pathways are TNFR1 Pathway and Senescence and autophagy in cancer. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and transcription cis-regulatory region binding. An important paralog of this gene is IRF6.

UniProtKB/Swiss-Prot Summary for IRF5 Gene

Transcription factor that plays a critical role in innate immunity by activating expression of type I interferon (IFN) IFNA and INFB and inflammatory cytokines downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9 (PubMed:11303025, 15695821, 22412986, 25326418, 32433612). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (By similarity). Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction downstream of the TLR-activated, MyD88-dependent pathway (By similarity). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). ( IRF5_HUMAN,Q13568 )

Protein attributes for IRF5 Gene

Size:498 amino acids

Molecular mass:56044 DaQuaternary structure:

Homodimer, when phosphorylated (PubMed:25326418, 18836453).

• Interacts with TASL (via pLxIS motif); interaction takes place downstream of TLR7, TLR8 or TLR9, leading to its activation (PubMed:32433612).
  Interacts with MYD88 and TRAF6 (By similarity).

 

See this image and copyright information in PMC

Figure 1

Work in progress hypothesis for the hyperinflammatory HBP-GlcNAc-OGT–IRF5-interferon-SARS-CoV-2 pathway leading to the cytokine storm.

 

Working Hypothesis for Glucose Metabolism and SARS-CoV-2 Replication: Interplay Between the Hexosamine Pathway and Interferon RF5 Triggering Hyperinflammation. Role of BCG Vaccine?

Hugo A. Laviada-Molina¹, Irene Leal-Berumen², Ernesto Rodriguez-Ayala³ and Raul A. Bastarrachea^4*

• ^{ONKO BCG  calmettointi  hyödyllinen asia  koronapandemiasta selviämisessä?   Tätä pohdittu seuraavassa artikkelissa vuodelta 2021:}

 https://pubmed.ncbi.nlm.nih.gov/33790587/

 eCollection 2021.

BCG Vaccine-Induced Trained Immunity and COVID-19: Protective or Bystander?

Gopala Koneru  ¹ , Gaber El-Saber Batiha 

 DOI: 10.2147/IDR.S300162 Free PMC article

Abstract

In late 2019, a new virulent coronavirus (CoV) emerged in Wuhan, China and was named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This virus spread rapidly, causing the coronavirus disease-2019 (COVID-19) pandemic. Bacillus Calmette-Guérin (BCG) is a live attenuated tuberculosis (TB) vaccine, associated with induction of non-specific cross-protection against unrelated infections. This protection is a memory-like response in innate immune cells (trained immunity), which is caused by epigenetic reprogramming via histone modification in the regulatory elements of specific genes in monocytes. COVID-19 related epidemiological studies showed an inverse relationship between national BCG vaccination policies and COVID-19 incidence and death, suggesting that BCG may induce trained immunity that could confer some protection against SARS-CoV-2. As this pandemic has put most of Earth's population under quarantine, repurposing of the old, well-characterized BCG may ensure some protection against COVID-19. This review focuses on BCG-related cross-protection and acquisition of trained immunity, as well as the correlation between BCG vaccination and COVID-19 incidence and mortality.

Keywords: BCG vaccine; COVID-19; coronavirus; trained immunity; tuberculosis. 

 

Kommentti: Post-pandemisen vaiheen  kansanterveystyössä olisi mielstäni suositeltavaa käynnistää vanhanaikainen  tubitarkastus eli niitä keuhkoröntgeneitä, koska tubilla ja covidilla on samantapainen  vaikutus immuunikarttaan ja kohde-elimen valintaan.   Ja molempien tautien yhteisvaikutustakin saataa esiintyä.  Ne tavalliset  kylästä kylään rullaavat minithorax-tutkimukset eivät ole mahdotonta toteuttaa. Calmettointikin on  suositeltavaa maailmassa. .