Hepatitis C virus RNA replication is resistant to tumour necrosis factor-alpha.
It was demonstrated using self-replicating hepatitis C virus (HCV) RNAs that both types of interferons (IFNs) (in particular IFN-alpha and IFN-gamma) are potent inhibitors of HCV replication in Huh-7 cells. Because IFN-gamma and tumour necrosis factor (TNF)-alpha trigger a partially overlapping set of antiviral defence mechanisms, it is tempting to speculate that TNF-alpha also inhibits HCV replication. However, this study shows that TNF-alpha does not affect HCV protein and RNA synthesis, nor does it synergistically enhance the inhibitory effect of IFN-gamma. Taken together, these results demonstrate that HCV replication in Huh-7 cells is highly resistant to TNF-alpha. It is, therefore, unlikely that the increased production of TNF-alpha, which is seen in many hepatitis C patients, contributes to HCV clearance by inducing antiviral defence mechanisms in infected hepatocytes.
Frese
Michael
M
Abteilung Molekulare Virologie, Hygiene Institut, Universität Heidelberg, Otto-Meyerhof-Zentrum, Im Neuenheimer Feld 350, D-69120 Heidelberg, Germany.|Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany.
Barth
Kerstin
K
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany.
Kaul
Artur
A
Abteilung Molekulare Virologie, Hygiene Institut, Universität Heidelberg, Otto-Meyerhof-Zentrum, Im Neuenheimer Feld 350, D-69120 Heidelberg, Germany.
Lohmann
Volker
V
Abteilung Molekulare Virologie, Hygiene Institut, Universität Heidelberg, Otto-Meyerhof-Zentrum, Im Neuenheimer Feld 350, D-69120 Heidelberg, Germany.
Schwärzle
Verena
V
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany.
Bartenschlager
Ralf
R
Abteilung Molekulare Virologie, Hygiene Institut, Universität Heidelberg, Otto-Meyerhof-Zentrum, Im Neuenheimer Feld 350, D-69120 Heidelberg, Germany.
D000998:Antiviral Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D012367:RNA, Viral / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma