Expression of RIG-I, IRF3, IFN-beta and IRF7 determines resistance or susceptibility of cells to infection by Newcastle Disease Virus.
Newcastle Disease Virus (NDV) is an avian paramyxovirus with anti-neoplastic and immune-stimulatory properties which has raised considerable interest for cancer therapy. To better understand the molecular nature of the tumor selective replication of NDV, we investigated the cellular responses of murine normal and tumor cells after infection by NDV. To this end, we compared the basal expression of different antiviral proteins as well as the expression induced by the addition of NDV to the cells in vitro and in vivo. Primary macrophages were found to be resistant to NDV infection and exhibited a high basal and induced expression of various antiviral genes. In contrast, macrophage-derived RAW tumor cells were highly susceptible to NDV infection and displayed a low expression of several antiviral genes. Macrophage-derived J774 tumor cells were intermediate with regard to NDV replication and antiviral gene expression. The responsiveness to exogenously added IFN-alpha was found highest in normal macrophages, lowest in the RAW cells, and intermediate in the J774 cells. We also analysed dendritic cells as well as additional normal and tumor cell types. A strong inverse correlation was obeserved between the susceptibility to infection and the basal expression of the antiviral genes RIG-I, IRF3, IRF7 and IFN-beta. A strong expression of these genes can explain the resistance of normal cells to NDV infection and a weak antiviral gene expression the broad susceptibility of tumor cells.
Wilden
Holger
H
Division of Cellular Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany.
Fournier
Philippe
P
Zawatzky
Rainer
R
Schirrmacher
Volker
V
D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D050838:Interferon Regulatory Factor-3 / Q000096:biosynthesis*; D050839:Interferon Regulatory Factor-7 / Q000096:biosynthesis*; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008957:Models, Genetic; D009522:Newcastle disease virus / Q000378:metabolism*; D012313:RNA / Q000378:metabolism
D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse; D012313:RNA; D016899:Interferon-beta