Interferons and Their Actions

Single-stranded RNA viruses inactivate the transcriptional activity of p53 but induce NOXA-dependent apoptosis via post-translational modifications of IRF-1, IRF-3 and CREB

“…Thus, recognition of conserved molecular motifs on viral components, including both single-stranded RNA (ssRNA) and double-stranded RNA (dsRNA), by pattern recognition receptors, such as Toll-like receptors (TLR), or the cytosolic RNA helicases RIG-1 and Mda5 (Meylan et al, 2005), results in the production of type I IFNs and other cytokines, that induce the production of specific proteins, that curtail the spread of virus by inducing an antiviral state in neighbouring cells. These cytokines also activate cellular immunity and the killing of virus-infected cells and play an important role in the establishment of the adaptive, antigen-specific immune response, culminating in the production of specific anti-viral antibodies and long-term protection to virus infection (Pestka et al, 1987;Biron et al, 1999). It is becoming increasingly apparent, however, that other mechanisms and in particular virus-induced apoptosis play a determinant role in limiting certain virus infections (Lyles, 2000).…”

Retinoic acid resistance in NB4 APL cells is associated with lack of interferon α synthesis Stat1 and p48 induction

“…Interferons (IFNs), classi®ed as a, b, or g on the basis of their antigenic properties, are a group of multifunctional cytokines that regulate cellular antiviral, anti-tumour and immunological responses (Pestka et al, 1987;Pfe er et al, 1998;Sen and Ransoho , 1993) through IFN-stimulated genes (ISG) expression. IFNs a and b (type I) are produced by many types of cells in response to viral infection, double stranded RNA treatment or other stimuli (De Maeyer and De Maeyer-Guignard, 1988).…”

Interferon-induces expression of cyclin-dependent kinase-inhibitors p21WAF1 and p27Kip1 that prevent activation of cyclin-dependent kinase by CDK-activating kinase (CAK)

“…Like most cytokines, IFNs must bind to speci®c high a nity cellular receptors to exert biological e ects. These e ects include regulation of expression of speci®c genes, antiviral properties, and inhibition of cell growth and proliferation (Sokawa, 1977;Pestka et al, 1987;Kumar and Atlas, 1992;Kumar et al, 1994;Yamada et al, 1994;Tiefenbrum et al, 1996). The inhibition of cell proliferation by IFNs is an active process, and generally involves arrest of cells in the G0/ G1-phase of the cell cycle.…”