PMID: 16979566, 16979568 It is now clear that all type I IFNs bind to the same dimeric receptor, but different type I IFNs elicit somewhat different biological responses. PMID: 16979566, 6175095 By the early 1980s, binding studies with radiolabeled IFN proteins had led to the conclusion that there are specific high-affinity cell-surface receptors for IFNs, that different subspecies of type I IFN (IFN-¦Á and IFN-beta) share a common receptor, and that receptors for type I and type II IFN are distinct.

PMID: 16979566, 4366491, 1067606 Two of the IFN-induced proteins central to IFN's antiviral actions, 2¡ì-5¡ì oligoadenylate synthetase and double-stranded RNA-dependent protein kinase (PKR), were shown to require double-stranded RNA for their activation.

PMID: 16979566, 4366491, 1067606 Two of the IFN-induced proteins central to IFN's antiviral actions, 2¡ì-5¡ì oligoadenylate synthetase and double-stranded RNA-dependent protein kinase (PKR), were shown to require double-stranded RNA for their activation.

PMID: 16979566, 4366491, 1067606 Two of the IFN-induced proteins central to IFN's antiviral actions, 2¡ì-5¡ì oligoadenylate synthetase and double-stranded RNA-dependent protein kinase (PKR), were shown to require double-stranded RNA for their activation.

PMID: 16979566, 11607032 Molecular pathways mediating cellular responses to double-stranded RNA remained largely unknown until the demonstration that toll-like receptor 3 (TLR3) recognizes double-stranded RNA. PMID: 16979566, 16979569 As explained in more detail in the accompanying review, this cytosolic pathway is functional mainly in specialized cells, namely dendritic cells (DCs).

PMID: 16979566, 16625202, 15208624 It is now apparent that the main pathway of type I IFN induction by double-stranded RNA and various RNA-containing viruses, which can be activated in a variety of cell types, is triggered by the cytosolic caspase-recruitment domain (CARD)-containing helicases RIG-I or MDA5.

PMID: 16979566, 16625202, 15208624 It is now apparent that the main pathway of type I IFN induction by double-stranded RNA and various RNA-containing viruses, which can be activated in a variety of cell types, is triggered by the cytosolic caspase-recruitment domain (CARD)-containing helicases RIG-I or MDA5.

PMID: 16979566 In addition to double-stranded RNA, other microbial components or products have been shown to trigger type I IFN production through other pathways, including single-stranded viral RNA (acting on TLR7 and TLR8) and viral or bacterial DNA (via TLR9).

PMID: 16979566 In addition to double-stranded RNA, other microbial components or products have been shown to trigger type I IFN production through other pathways, including single-stranded viral RNA (acting on TLR7 and TLR8) and viral or bacterial DNA (via TLR9).

PMID: 16979566 In addition to double-stranded RNA, other microbial components or products have been shown to trigger type I IFN production through other pathways, including single-stranded viral RNA (acting on TLR7 and TLR8) and viral or bacterial DNA (via TLR9).

PMID: 16979566 In addition to double-stranded RNA, other microbial components or products have been shown to trigger type I IFN production through other pathways, including single-stranded viral RNA (acting on TLR7 and TLR8) and viral or bacterial DNA (via TLR9).

PMID: 16979566, 6175095 By the early 1980s, binding studies with radiolabeled IFN proteins had led to the conclusion that there are specific high-affinity cell-surface receptors for IFNs, that different subspecies of type I IFN (IFN-¦Á and IFN-beta) share a common receptor, and that receptors for type I and type II IFN are distinct.

PMID: 16979566 In addition to double-stranded RNA, other microbial components or products have been shown to trigger type I IFN production through other pathways, including single-stranded viral RNA (acting on TLR7 and TLR8) and viral or bacterial DNA (via TLR9).

PMID: 16979566 In addition to double-stranded RNA, other microbial components or products have been shown to trigger type I IFN production through other pathways, including single-stranded viral RNA (acting on TLR7 and TLR8) and viral or bacterial DNA (via TLR9).

PMID: 16979566, 16410796, 16979569 Although nucleic acids are arguably the most important activators of type I IFN production, bacterial LPS is now known to trigger IFN production in macrophages and DCs via TLR4.

PMID: 16979566, 16410796, 16979569 Although nucleic acids are arguably the most important activators of type I IFN production, bacterial LPS is now known to trigger IFN production in macrophages and DCs via TLR4.

PMID: 16979566, 11244049 The earliest-discovered members of this family, IRF-1 and IRF-2, were shown to be important in a variety of innate and adaptive immune responses, including T helper 1 responses and natural killer (NK) cell differentiation.

PMID: 16979566, 11244049 The earliest-discovered members of this family, IRF-1 and IRF-2, were shown to be important in a variety of innate and adaptive immune responses, including T helper 1 responses and natural killer (NK) cell differentiation.

PMID: 16979566, 9707562, 9822609 Two other members of the IRF family, IRF-3 and IRF-7, have been found to play key roles in type I IFN gene activation.

PMID: 16979566, 9707562, 9822609 Two other members of the IRF family, IRF-3 and IRF-7, have been found to play key roles in type I IFN gene activation.

PMID: 16979566, 15665823 For example, MyD88-dependent activation of IRF-5 is essential for the TLR-mediated induction of the proinflammatory cytokines TNF-alpha, IL-6, and IL-12, but not for IFN-alpha and IFN-beta induction.

PMID: 16979566, 15665823 For example, MyD88-dependent activation of IRF-5 is essential for the TLR-mediated induction of the proinflammatory cytokines TNF-alpha, IL-6, and IL-12, but not for IFN-alpha and IFN-beta induction.

PMID: 16979566, 8197455 Gradual elucidation of the details of the JAK-STAT signaling pathway activated by IFNs helped to clarify not only the molecular mechanisms responsible for IFN actions, but also laid the groundwork for understanding the actions of many other cytokines.

PMID: 16979566, 15665823 For example, MyD88-dependent activation of IRF-5 is essential for the TLR-mediated induction of the proinflammatory cytokines TNF-alpha, IL-6, and IL-12, but not for IFN-alpha and IFN-beta induction.

PMID: 16979566, 15665823 For example, MyD88-dependent activation of IRF-5 is essential for the TLR-mediated induction of the proinflammatory cytokines TNF-alpha, IL-6, and IL-12, but not for IFN-alpha and IFN-beta induction.

PMID: 16979566, 15665823 For example, MyD88-dependent activation of IRF-5 is essential for the TLR-mediated induction of the proinflammatory cytokines TNF-alpha, IL-6, and IL-12, but not for IFN-alpha and IFN-beta induction.

PMID: 16979566, 8197455 Gradual elucidation of the details of the JAK-STAT signaling pathway activated by IFNs helped to clarify not only the molecular mechanisms responsible for IFN actions, but also laid the groundwork for understanding the actions of many other cytokines.

PMID: 16979566, 8197455 Gradual elucidation of the details of the JAK-STAT signaling pathway activated by IFNs helped to clarify not only the molecular mechanisms responsible for IFN actions, but also laid the groundwork for understanding the actions of many other cytokines.

PMID: 16979566, 17838106 IFN-gamma owes its discovery to the finding that the addition of phytohemagglutinin, a mitogenic lectin, to a suspension of human leucocytes elicited IFN production.

PMID: 16979566, 5233831 Double-stranded RNA from statolon or helenine, and also synthetic double-stranded RNA, poly (I).poly(C), readily triggered IFN production in intact animals or in cell cultures.

PMID: 16979566, 5233831 Double-stranded RNA from statolon or helenine, and also synthetic double-stranded RNA, poly (I).poly(C), readily triggered IFN production in intact animals or in cell cultures.

PMID: 16979566, 4366491, 1067606 Two of the IFN-induced proteins central to IFN's antiviral actions, 2¡ì-5¡ì oligoadenylate synthetase and double-stranded RNA-dependent protein kinase (PKR), were shown to require double-stranded RNA for their activation.