Interferons, Mx genes, and resistance to influenza virus.
Human influenza is primarily an infection of the upper respiratory tract and central airways. The interferon (IFN) system appears to have a role in limiting viral spread and initiating recovery before the development of T-cell and B-cell responses in primary infection. All cellular responses to IFNs result from interaction with cell surface receptors that trigger the expression of a number of cellular genes. Among the IFN-inducible gene products, the Mx proteins have attracted much attention because they have potential activity against influenza virus and possibly against other viruses. Mx proteins are guanosine triphosphate (GTP)-binding proteins with intrinsic GTPase activity. They seem to act indirectly against viruses by modifying cellular functions needed along the viral replication pathway. In mice the Mx1 protein has been shown to be necessary and sufficient to protect against influenza virus infection because the resistance does not require a functioning immune system. In humans the MxA protein has antiviral activities against influenza viruses. The MxA protein is encoded on the distal part of the long arm of chromosome 21 together with several other proteins implicated in the IFN system. Patients with Down's syndrome (trisomy 21) have an increased expression of MxA protein, and their cells display an increased sensitivity to IFNs in vitro because of gene dosage effects. These patients, however, are more susceptible to upper respiratory infection than normal individuals. This susceptibility has been related to deficiencies in the immune system. Therefore, induction of MxA in man does not sem sufficient to prevent influenza spreading, and, in contrast to the murine Mx system, a functioning immune system is necessary for protection.
Horisberger
M A
MA
Department of Core Drug Discovery Technologies, Ciba-Geigy Ltd., Basel, Switzerland.
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000235:genetics / Q000276:immunology*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D019204:GTP-Binding Proteins; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology*; D007372:Interferons / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D064547:Myxovirus Resistance Proteins; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology*; D011506:Proteins / Q000235:genetics / Q000276:immunology*
D000998:Antiviral Agents; C579071:MX1 protein, human; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D007372:Interferons; D019204:GTP-Binding Proteins