[Alpha interferon, antiviral proteins and their value in clinical medicine].
Type I interferon system is an important part of host's innate defense mechanisms against viral infections. The type I interferons mediate in part their antiviral effect via induction of various proteins. Among them the most widely known are 2'-5' oligoadenylate synthetase (2'-5' OAS) and a protein kinase (PKR). MxA, an other antiviral protein, is specifically induced by the type I interferons. The MxA protein contains the dynamin signature, which is implicated in transport processes. The MxA protein appears to block the replication of certain viruses at poorly defined steps. There are substantial differences in the antiviral activity of MxA between virus types. Indeed, the replication of vesicular stomatitis virus and influenza virus is inhibited by MxA, but not the one of type I herpes simplex virus. Measurements of interferon alpha and MxA levels may be of high value in clinical practice. Interferon alpha can be detected by using a bioassay based on the interferon alpha ability to protect cultured cells from the cytopathic effect caused by a selected challenged virus, or by using immunological techniques. The current bioassays are the most sensitive methods but they are cumbersome and lengthy, even though simplifications have been proposed. Immunological techniques are easier, however they do not explore the biological activity of the circulating interferon. The presence of type I interferon in biological samples (serum, plasma, cerebro-spinal fluid, cultured cell supernatants) can be indirectly assessed by capability of interferon alpha to induce in vitro the synthesis of MxA in a dose dependent manner in cultured cells. Following to the lysis of the cells, the induced MxA can be quantitated and hence the type I-interferon concentration can be determinated in samples. The quantitation of MxA protein in peripheral blood lysates can be useful as a specific marker of acute viral infections. A minute amount of whole blood (15 mul) is sufficient which facilitates its use in pediatrics. The specifically type-I-interferons inducible MxA protein is also a potential useful marker in the management of interferon alpha-treatment. Moreover, the detection of interferon alpha and antiviral proteins constitute an indirect approach for investigating the hypothesis of the role of viruses in chronic diseases with suspected infectious aetiology.
Chieux
V
V
Laboratoire de virologie, Institut Gernez-Rieux, Centre hospitalier et universitaire, 59037 Lille cedex.
Hober
D
D
Chehadeh
W
W
Wattré
P
P
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis; D000818:Animals; D000998:Antiviral Agents / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D002478:Cells, Cultured / Q000378:metabolism / Q000821:virology; D002648:Child; D002908:Chronic Disease; D003588:Cytopathogenic Effect, Viral; D004790:Enzyme Induction; D020558:GTP Phosphohydrolases / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D064547:Myxovirus Resistance Proteins; D009975:Orthomyxoviridae / Q000276:immunology; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000096:biosynthesis; D011506:Proteins / Q000276:immunology* / Q000378:metabolism; D018139:Simplexvirus / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology* / Q000378:metabolism; D014779:Virus Replication; D014780:Viruses / Q000276:immunology*
D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D011494:Protein Kinases; D015088:2',5'-Oligoadenylate Synthetase; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins