Mx1 gene protects mice against the highly lethal human H5N1 influenza virus.
We investigated the importance of the host Mx1 gene in protection against highly pathogenic H5N1 avian influenza virus. Mice expressing the Mx1 gene survived infection with the lethal human H5N1 isolate A/Vietnam/1203/04 and with reassortants combining its genes with those of the non-lethal virus A/chicken/Vietnam/C58/04, while all Mx1-/- mice succumbed. Mx1-expressing mice showed lower organ virus titers, fewer lesions, and less pulmonary inflammation. Our data support the hypothesis that Mx1 expression protects mice against the high pathogenicity of H5N1 virus through inhibition of viral polymerase activity ultimately resulting in reduced viral growth and spread. Drugs that mimic this mechanism may be protective in humans.
Salomon
Rachelle
R
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA.
Staeheli
Peter
P
Kochs
Georg
G
Yen
Hui-Ling
HL
Franks
John
J
Rehg
Jerold E
JE
Webster
Robert G
RG
Hoffmann
Erich
E
D000818:Animals; D002645:Chickens; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000378:metabolism*; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D064547:Myxovirus Resistance Proteins; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D014764:Viral Proteins / Q000378:metabolism*
C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D014764:Viral Proteins; D019204:GTP-Binding Proteins