IFIH1
IFIH1 (interferon induced with helicase C domain 1), also known as MDA-5, MDA5 and Hlcd, is a cytoplasmic innate immune receptor that senses viral nucleic acids. Detection of viral RNA triggers antiviral signalling, including induction of type I interferons and pro-inflammatory cytokines. Browse Assay Genie's current range of IFIH1 research reagents below, or read on for the biology behind the target.
IFIH1 acts as a cytoplasmic sensor of viral infection. Its ligands include mRNA lacking 2'-O-methylation at the 5' cap and long double-stranded RNA longer than 1 kb. Following ligand binding, it associates with the mitochondrial antiviral signalling protein MAVS (IPS1), which activates the IKK-related kinases TBK1 and IKBKE. These phosphorylate interferon regulatory factors IRF3 and IRF7, which drive transcription of antiviral genes, including IFN-alpha and IFN-beta. IFIH1 also amplifies innate immune signalling by recognising RNA metabolites produced by ribonuclease L (RNase L) during infection.
The protein detects Picornaviridae members such as encephalomyocarditis virus and rhinovirus, as well as dengue virus, West Nile virus, reovirus and SARS-CoV-2. It also contributes to antiviral signalling against dsDNA viruses such as vaccinia virus. According to the NCBI Gene summary, MDA5 senses RNA length and secondary structure, binding dsRNA through a modified DExD/H-box helicase core and a C-terminal domain. Coronaviruses and other virus families can evade the MDA5-dependent interferon response. UniProt places the protein in the helicase family, RLR subfamily; HGNC lists it within the RIG-I RNA sensor family and the caspase recruitment domain containing group. The enzyme is classed as EC 3.6.4.13, and UniProt reports localisation to the cytoplasm, nucleus and mitochondrion.
Beyond antiviral defence, IFIH1 may enhance natural killer cell function, including in malaria infection, and may be involved in growth inhibition and apoptosis in several tumour cell lines. The IFIH1 gene has been implicated in autoimmune and autoinflammatory diseases, including type 1 diabetes, systemic lupus erythematosus and Aicardi-Goutieres syndrome; IDDM19 is a listed alias. The mouse ortholog is Ifih1.
IFIH1 senses viral RNA in the cytoplasm and initiates interferon and cytokine responses, making it central to studies of early host defence.
Signalling runs through MAVS, TBK1, IKBKE, IRF3 and IRF7 to IFN-alpha and IFN-beta, allowing dissection of this cascade.
IFIH1 is implicated in type 1 diabetes, systemic lupus erythematosus and Aicardi-Goutieres syndrome, linking RNA sensing to autoinflammation.
Coronaviruses and other virus families can evade the MDA5-dependent interferon response, so IFIH1 is relevant to how pathogens escape detection.
IFIH1 is a cytoplasmic sensor of viral RNA. On binding long dsRNA or mRNA lacking 5' cap 2'-O-methylation, it signals through MAVS, TBK1 and IKBKE to IRF3 and IRF7, inducing type I interferons and pro-inflammatory cytokines.
IFIH1 is the HGNC symbol for interferon induced with helicase C domain 1. The protein is widely called MDA5 or MDA-5, and aliases include Hlcd and IDDM19. UniProt names it interferon-induced helicase C domain-containing protein 1.
Yes. The NCBI Gene summary notes that MDA5 has been implicated in type 1 diabetes, systemic lupus erythematosus and Aicardi-Goutieres syndrome. The mouse ortholog is Ifih1; check the datasheet of any product for its validated reactivity.
Other RNA sensors, signalling kinases, interferon regulatory factors and interferons that act alongside IFIH1 in antiviral responses.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9BYX4; product specifications from Assay Genie datasheets.