Disease relevance of If1

• The levels of circulating IFN in mice infected with Newcastle disease virus (NDV) are regulated by the If-1 locus [1].
• These data suggest that the If-1 allele may influence the somnogenic responsiveness of mice under some conditions but that additional mechanisms may contribute to sleep enhancement during infectious disease [2].
• To evaluate the contribution of the If-1 gene to differences in murine sleep propensity, sleep patterns were evaluated in mice treated with the IFN inducers polyinosinic:polycytidilic acid (pIC) or Newcastle disease virus (NDV), with influenza virus, or with murine interferon (IFN-alpha) or IFN-alpha/beta [2].

High impact information on If1

• A surprise finding was that the If-1 locus also affected the NDV-induced expression of two other cytokine genes, TNF-alpha and IL-6 [1].
• The relative levels of all individual IFN-alpha 1, alpha 4, and alpha 6 mRNA in spleens of infected BALB/c were lower than in spleens of infected C57BL/6 mice, indicating that the If-1 locus affects the expression of all IFN-alpha subtypes and is not associated with the deletion or inactivation of a specific IFN gene [1].
• Regulation of interferon gene expression: mechanism of action of the If-1 locus [3].
• Higher levels of DNA-binding/transcription factors found in nuclei from spleen cells of If-1h mice may be involved in the expression of the If-1 phenotype [4].
• Only BMM but not spleen lymphocytes showed allele-specific differences in NDV-induced cytokine levels, indicating cell-specific If-1 expression [5].

Biological context of If1

• Downregulation of Newcastle disease virus (NDV)-dependent IFN-alpha/beta production in macrophages by IFN-induced gene products of the locus If-1 [6].
• A subtractive cDNA library was used to identify differentially expressed genes in mouse strains that differ at If1, a locus that regulates response to interferon induction by Newcastle Disease Virus infection [7].

Anatomical context of If1

• In macrophages from inbred mice, the magnitude of the interferon (IFN) response to Newcastle disease virus (NDV) infection is under genetic control of the If-1 locus, which carries the allele for either high (h) or low (l) IFN production [8].
• Thus DH to NDV is determined on the one hand by the alleles at If-1, influencing interferon production, and on the other hand by a combination of several genes affecting the interaction of interferon with cells of the immune system [9].

Associations of If1 with chemical compounds

• The If-1 locus harbors IFN-inducible gene(s) whose expression is prevented in the presence of cycloheximide [5].

Other interactions of If1

• We have found that in cultured mouse bone-marrow-derived macrophages (BMDM), endogenous IFN-beta specifically regulates Newcastle disease virus (NDV) induced interferon (IFN)-alpha/beta synthesis, possibly by influencing the activity of genes within the regulatory locus If-1 [6].

References