Virus-specific interferon action. Protection of newborn Mx carriers against lethal infection with influenza virus.

Abstract

The efficacy of interferon in antiviral protection of newborn mice differing at the Mx locus was investigated. Adult mice bearing the allele Mx exhibit a high degree of specific resistance toward lethal challenge with influenza viruses. In contrast, newborn Mx carriers are virtually as susceptible to influenza viruses as newborn mice devoid of Mx. Resistance can be abrogated by treating adult animals with anti-interferon serum. Here, we provide direct evidence of a virus-specific effect of interferon in vivo: newborn mice carrying the resistance gene Mx could be protected against lethal influenza virus infection with doses of interferon that were not protective in the absence of Mx. The efficacy of interferon towards a picornavirus (encephalomyocarditis virus) and a rhabdovirus (vesicular stomatitis virus) was independent of Mx.

Interferon-Induced Expression of MxA in the Respiratory Tract of Rhesus Macaques Is Suppressed by Influenza Virus Replication

“…Haller et al demonstrated that in the presence of IFN, mice with a functional Mx1 gene, the murine homologue of the human MxA gene, were more likely to survive a lethal influenza virus challenge than mice without a functional Mx1 gene (3). IFN-␣ is required to induce the Mx1-mediated influenza virus resistance, because treatment of mice with an anti-IFN Ab eliminates the beneficial effect of the intact Mx1 gene (3,24,25). However, the role of IFN-induced MxA in controlling influenza virus replication in humans and other animals is unclear.…”

“…Induction of IFN-␣␤ occurs after TLRs, the retinoic acidinducible gene I (RIG-I), or the melanoma differentiation-associated gene 5 (MDA-5) bind dsRNA or ssRNA, leading to the activation of IFN-regulatory factors 3 and 7 (IRF-3 and IRF-7), NF-B, and AP-1 (35)(36)(37). Secreted IFN-␣␤ binding to the IFN-␣ receptor activates ISG factor 3 (ISGF3), which binds the ISRE (3,24,35). ISGF3 binding to ISRE activates the transcription of MxA.…”

“…Innate immune responses are especially critical for controlling influenza virus replication. IFNstimulated genes (ISGs) 3 play a central role in innate antiviral immunity (2). Among the ISGs, myxovirus resistance (Mx) proteins were originally identified as factors conferring resistance to lethal influenza A virus infections in mice (3).…”

“…IFNstimulated genes (ISGs) 3 play a central role in innate antiviral immunity (2). Among the ISGs, myxovirus resistance (Mx) proteins were originally identified as factors conferring resistance to lethal influenza A virus infections in mice (3). The human Mx homologue MxA is able to inhibit the replication of orthomyxoviruses and other RNA viruses (reviewed in Ref.…”

Interferon-induced human protein with homology to protein Mx of influenza virus-resistant mice.

“…We believe the 2C12-cross-reacting protein most likely is the human homolog of protein Mx (3,4,13). The significance of the homologous human protein for host defense of humans against influenza viruses is less clear and remains to be investigated.…”