Avian cells expressing the murine Mx1 protein are resistant to influenza virus infection.
The cDNA encoding the murine Mx1 protein, a mediator of resistance to influenza virus, was inserted into a replication-competent avian retroviral vector in either the sense (referred to as Mx+) or the antisense (referred to as Mx-) orientation relative to the viral structural genes. Both vectors produced virus retaining the Mx insert (Mx recombinant viruses referred to as Mx+ and Mx-) following transfection into chicken embryo fibroblasts (CEF). Mx protein of the appropriate size and nuclear localization was expressed only in CEF cells infected with the Mx+ virus. Mx expression was observed in all Mx(+)-infected cells and was stable during long-term culture. Cells infected with the Mx+ virus were resistant to infection by human influenza A/WSN/33 (H1N1) and avian influenza viruses A/Turkey/Wisconsin/68 (H5N9) and A/Turkey/Massachusetts/65 (H6N2), but were susceptible to infection by the enveloped RNA viruses Sindbis and vesicular stomatitis virus (VSV). Normal CEF and cells infected with the Mx virus were susceptible to influenza A, Sindbis, and VSV. The synthesis of influenza proteins, especially the larger polymerase and hemagglutinin proteins, was reduced in Mx+ retrovirus-infected cells superinfected by influenza A.
Garber
E A
EA
Department of Animal Biochemistry and Molecular Biology, Merck, Sharp, and Dohme Research Laboratories, Rahway, New Jersey 07065.
Chute
H T
HT
Condra
J H
JH
Gotlib
L
L
Colonno
R J
RJ
Smith
R G
RG
D000818:Animals; D000998:Antiviral Agents / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D002642:Chick Embryo; D005347:Fibroblasts / Q000166:cytology; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins; D020022:Genetic Predisposition to Disease; D015151:Immunoblotting; D009980:Influenza A virus / Q000254:growth & development*; D051379:Mice; D008815:Mice, Inbred Strains; D064547:Myxovirus Resistance Proteins; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D010948:Viral Plaque Assay
D000998:Antiviral Agents; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D019204:GTP-Binding Proteins