What does MDA5 bind to?
What does MDA5 bind to?
During viral infection, the CTD of RIG-I/MDA5 binds to viral RNA, leading to activation of CARD domains followed by activation of MAVS to trigger downstream signaling (Loo and Gale, 2011).
How does MDA5 work?
Melanoma Differentiation-Associated gene 5 (MDA5), encoded by the gene IFIH1, is a cytoplasmic sensor for viral double-stranded RNAs (dsRNAs). MDA5 activates the type I interferon signaling pathway upon detection of long viral dsRNA generated during replication of picornaviruses.
How is MDA5 activated?
It is generally assumed that MDA5 is activated by long molecules of double-stranded RNA (dsRNA) produced by annealing of complementary RNAs generated during viral infection.
What is rig-I and MDA5?
RIG-I and MDA5 are the principal sensors of viral dsRNA in the cytoplasm. The interferon-dependent inflammatory response triggered by RLR ligand binding is one of the first and most important lines of defense against infection. RIG-I and MDA5 recognize distinct and complementary sets of viral dsRNA ligands.
What is MDA5 antibody?
The MDA5 antibody, also known as an anti-CADM-140 antibody, has especially been associated with CADM [6], and has been used to detect dermatopulmonary syndrome in patients who have undergone allogeneic hematopoietic stem cell transplantation [9] or in patients with DM [10, 11].
What does MDA5 stand for?
MDA5 (melanoma differentiation-associated protein 5) is a RIG-I-like receptor dsRNA helicase enzyme that is encoded by the IFIH1 gene in humans.
Is MDA5 genetic?
MDA5 (melanoma differentiation-associated protein 5) is a RIG-I-like receptor dsRNA helicase enzyme that is encoded by the IFIH1 gene in humans. MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2, and functions as a pattern recognition receptor capable of detecting viruses.
What does Rig 1 recognize?
RIG-I is an essential molecule in the innate immune system for recognizing cells that have been infected with a virus. These viruses can include West Nile virus, Japanese Encephalitis virus, influenza A, Sendai virus, flavivirus, and coronaviruses.
How rare is MDA5 dermatomyositis?
Juvenile Dermatomyositis Associated With Anti-MDA5 Antibodies. Juvenile DM (JDM) is associated with anti-MDA5 Abs in 6 to 12% of cases in European and North American cohorts, and constitutes the third most frequent DM-associated Abs after anti-TIF1γ and anti-NXP2 Abs (56, 58–62).
How rare is MDA5?
Anti-MDA5 DM is a rare disease representing less than 2% of IIM in Europe (3). Among the subgroup of DM, the prevalence of anti-MDA5 DM ranges from 7 to 60%, with higher prevalence in Asian (11-60%) than in Caucasian (7-16%) (Table 1) (1, 4–19).
What are the symptoms of MDA5?
Symptoms
- Fast developing lung manifestation (and breathing difficulties)
- Ulcerations (wounds) and panniculitis (adipose tissue inflammation) in the skin.
- Swollen hands. Often with wounds. Knots in the palms.
- Arthritis (inflammed joints)
- Mouth ulcers.
- Alopecia (hair loss)
What is MDA5 dermatomyositis?
Anti-MDA5-associated dermatomyositis (MDA5-associated DM) is an uncommon presentation of idiopathic inflammatory myositis, typically amyopathic, associated with rapidly progressive, treatment refractory interstitial lung disease and poor prognosis, particularly in patients with concomitant rapidly progressive …
What is the molecular nature of MDA5 ligand?
The molecular nature of the MDA5 ligand remains poorly characterized. The stereotypic MDA5 agonist is polyI:C ( Gitlin et al., 2006; Kato et al., 2006 ), a synthetic RNA molecule lacking 5′-triphosphates that is generated by the annealing of poly-inosine strands to poly-cytidine strands of various lengths.
Do RIG-I and MDA-5 bind the same dsRNA?
However, it is admitted that RIG-I and MDA-5 exhibit a different dependency for the length of dsRNAs: RIG-I selectively binds short dsRNA while MDA-5 selectively binds long dsRNA. Consistent with this, RIG-I and MDA-5 bind Poly (I:C), a synthetic dsRNA analog, with different length predilection [3] .
What is the mechanism of stimulation of RIG-I and MDA5?
Stimulation of RIG-I and MDA5 results in the binding of the RLRs to the signaling adaptor MAVS, which leads to the activation of NF-κB and the induction of a TBK1 and IRF3-mediated type I interferon response.
What does MDA-5 stand for?
RIG-I (retinoic-acid-inducible protein 1, also known as Ddx58) and MDA-5 (melanoma-differentiation-associated gene 5, also known as Ifih1 or Helicard) are cytoplasmic RNA helicases that belong to the RIG-I-like receptors (RLRs) family and are critical for host antiviral responses [1] .
