Interferon Deficiency Syndrome

Abstract

Activation of the interferon (IFN) system is an early defence mechanism against viral infections. The virus stimulates production of IFN by nucleated cells including the peripheral blood mononuclear cells (PBMC), and this IFN in turn activates several IFN-dependent immune mechanisms including the induction of an anti-viral state in cells, which prevents or retards further intracellular viral replication. In an ongoing study of 1,500 individuals of all ages and with various illnesses, we found 15 cases (representing 5% of patients with acute viral disease) in whom the IFN system response during an acute viral illness was absent or grossly deficient. There was no detectable IFN in the blood, PBMC did not produce IFN-a and IFN-y or produced minimal amounts of one ofthem in vitro following appropriate stimulation, and the patients' PBMC were not in an anti-viral state. These patients had severe progressive or fulminant viral disease, often ending fatally. IFN therapy appears to be beneficial in these cases, as it rapidly induced a cellular antiviral state in most cases, stimulated in vitro IFN-cc and IFN-y production by PBMC, and led to rapid recovery in seven of the nine patients who received treatment for at least 3 days. In our opinion IFN replacement therapy should be commenced as early as possible in such cases, and before irreversible cell and organ damage occur. Keywords interferon peripheral blood mononuclear cells vesicular stomatitis virus poly-inosinic-cytidilic acid phytohaemagglutinin cytopathogenic effect

A systematic approach to virus–virus interactions

“…Activation of both enzymes is dependent on the presence of molecules associated with infection, particularly dsRNA, and their activation usually results in cell death (Staeheli, 1990). Animals with defective type I interferon signaling pathways, PKR, or 2 -5 OAS are much more susceptible to viral infections, indicating the effectiveness of the antiviral state (Levin and Hahn, 1985). However, most viruses have also evolved antagonists of PKR and or 2 -5 OAS (Hengel et al, 2005;Langland et al, 2006;Levy and Garcia-Sastre, 2001).…”

Transgenic models for cytokine-induced neurological disease

“…The type I IFN family contains multiple members, including several IFN-α isoforms and a single IFN-β that are produced by various cell types. Deficiencies in type I IFN function render humans [94, 95] and mice [96, 97] highly susceptible to viral infection highlighting their integral role in host defence. In contrast, IFN-γ is the only member of the type II IFN family.…”

Genetic susceptibility and resistance to influenza infection and disease in humans and mice

“…In humans, IFN deficiency syndromes, rather than Mx1 variants, may be more relevant to influenza resistance [104]. For example, deficiencies in IFNα have been reported in association with hyper-IgM disease caused by mutations in the CD40 gene [105,106] TLRs are a group of pattern-recognition receptors that interact with microbial components collectively known as pathogenassociated molecular patterns (PAMPs) to limit or eradicate invading microbes. Binding of PAMPs such as peptidoglycan, LPS or dsRNA to the appropriate TLR induces the production of reactive oxygen and nitrogen intermediates, initiates the proinflammatory cytokine network, and induces costimulatory molecules that link the innate immune response to adaptive immunity [107,108].…”