Dozens of genes are upregulated by the ISGF3 transcription factor complex. The following represents some genes that are commonly upregulated in cells responding to type I interferon (IFN) along with their antiviral mechanisms:
- IFIT1 (Interferon-induced protein with tetratricopeptide repeats 1):
- The IFIT1 gene is also known as ISG56.
- IFIT1 inhibits viral translation by binding to viral mRNA and preventing ribosome assembly, thereby suppressing viral protein synthesis.
- OAS1 (2′-5′-oligoadenylate synthetase 1):
- OAS1 catalyzes the synthesis of 2′-5′-oligoadenylates (2-5A) upon activation by dsRNA. 2-5A molecules activate the latent ribonuclease RNase L, leading to degradation of viral RNA and inhibition of viral replication.
- MX1 (Myxovirus resistance protein 1):
- MX1 interferes with various stages of the viral replication cycle, including viral entry, transcription, and nuclear export. It acts by forming oligomeric structures that bind to viral nucleocapsids, preventing their nuclear import and subsequent replication.
- ISG15 (Interferon-stimulated gene 15):
- ISG15 conjugates to target proteins, a process known as ISGylation, leading to their modification and alteration of their function. ISG15ylation can interfere with viral replication by targeting viral proteins for degradation or modifying host proteins involved in viral replication processes.
- RSAD2 (Radical S-adenosyl methionine domain-containing protein 2):
- RSAD2 encodes the protein “Viperin”.
- RSAD2/Viperin inhibits the replication of a broad range of viruses by interfering with various steps of the viral life cycle, including viral assembly, budding, and maturation. It disrupts lipid rafts in the cell membrane, which are important for viral assembly and release.
- IFIH1 (Interferon-induced helicase C domain-containing protein 1):
- IFIH1 encodes the protein “MDA5”.
- IFIH1/MDA5 functions as a cytosolic sensor of viral RNA, particularly dsRNA. Upon recognition of viral RNA, MDA5 activates downstream signaling pathways, leading to the production of type I IFNs and the induction of antiviral genes.
- STAT1 (Signal transducer and activator of transcription 1):
- STAT1 is a key transcription factor that mediates the cellular response to type I IFNs. Upon phosphorylation and dimerization, STAT1 translocates to the nucleus and binds to ISREs in the promoters of target genes, including other IFN-stimulated genes involved in antiviral defense.
- IRF7 (Interferon regulatory factor 7):
- IRF7 is a transcription factor that plays a critical role in the amplification of type I IFN responses. It is induced by type I IFNs and activates the transcription of additional IFN genes, thereby amplifying the antiviral response.
- EIF2AK2 (Eukaryotic translation initiation factor 2-alpha kinase 2):
- The EIF2AK2 gene encodes protein kinase R (PKR).
- PKR is activated by dsRNA and phosphorylates the eukaryotic translation initiation factor eIF2α, leading to inhibition of protein synthesis and suppression of viral replication. PKR also activates NF-κB and IRF3, contributing to the production of type I IFNs and other pro-inflammatory cytokines.
- TRIM25 (Tripartite motif-containing protein 25):
- TRIM25 is an E3 ubiquitin ligase that catalyzes the ubiquitination and activation of RIG-I, leading to the induction of type I IFNs and the expression of antiviral genes.
These genes represent a subset of the diverse array of interferon-stimulated genes (ISGs) that are upregulated in response to type I IFNs. They collectively contribute to the host’s innate antiviral defense mechanisms by targeting various stages of the viral replication cycle, modulating host cell signaling pathways, and promoting an antiviral state within infected cells.
End of Section 2.4
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Source: ChatGPT response prompted and edited by Joel Graff.
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