Human MxA Protein Protects Mice Lacking a Functional Alpha/Beta Interferon System against La Crosse Virus and Other Lethal Viral Infections
| Autor: | Hans Peter Hefti, Michael Frese, Adriano Aguzzi, Heinrich Landis, Otto Haller, Claudio Di Paolo, Jovan Pavlovic |
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| Přispěvatelé: | University of Zurich, Pavlovic, J |
| Rok vydání: | 1999 |
| Předmět: |
Myxovirus Resistance Proteins
1109 Insect Science La Crosse virus viruses Immunology 10208 Institute of Neuropathology 610 Medicine & health Mice Transgenic Receptor Interferon alpha-beta Semliki Forest virus Antiviral Agents Microbiology Virus Mice Encephalitis California Orthomyxoviridae Infections GTP-Binding Proteins In vivo Interferon Virology medicine Animals Humans Receptors Interferon Mice Knockout 2403 Immunology Mice Inbred BALB C biology Alphavirus Infections 2404 Microbiology Interferon-alpha Membrane Proteins Proteins RNA Interferon-beta biology.organism_classification Semliki forest virus Titer Viral replication Protein Biosynthesis Insect Science 2406 Virology 570 Life sciences Pathogenesis and Immunity Thogotovirus medicine.drug |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.73.8.6984-6991.1999 |
| Popis: | The human MxA protein is part of the antiviral state induced by alpha/beta interferon (IFN-α/β). MxA inhibits the multiplication of several RNA viruses in cell culture. However, its antiviral potential in vivo has not yet been fully explored. We have generated MxA-transgenic mice that lack a functional IFN system by crossing MxA-transgenic mice constitutively expressing MxA with genetically targeted (knockout) mice lacking the β subunit of the IFN-α/β receptor (IFNAR-1 −/− mice). These mice are an ideal animal model to investigate the unique antiviral activity of human MxA in vivo, because they are unable to express other IFN-induced proteins. Here, we show that MxA confers resistance to Thogoto virus, La Crosse virus, and Semliki Forest virus. No Thogoto virus progeny was detectable in MxA-transgenic mice, indicating an efficient block of virus replication at the primary site of infection. In the case of La Crosse virus, MxA restricted invasion of the central nervous system. In contrast, Semliki Forest virus multiplication in the brain was detectable in both MxA-expressing and nonexpressing IFNAR-1 −/− mice. However, viral titers were clearly reduced in MxA-transgenic mice. Our results demonstrate that MxA does not need the help of other IFN-induced proteins for activity but is a powerful antiviral agent on its own. Moreover, the results suggest that MxA may protect humans from potential fatal infections by La Crosse virus and other viral pathogens. |
| Databáze: | OpenAIRE |
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