Anti-retroviral effects of type I IFN subtypes in vivo.
Type I IFN play a very important role in immunity against viral infections. Murine type I IFN belongs to a multigene family including 14 IFN-alpha subtypes but the biological functions of IFN-alpha subtypes in retroviral infections are unknown. We have used the Friend retrovirus model to determine the anti-viral effects of IFN-alpha subtypes in vitro and in vivo. IFN-alpha subtypes alpha1, alpha4, alpha6 or alpha9 suppressed Friend virus (FV) replication in vitro, but differed greatly in their anti-viral efficacy in vivo. Treatment of FV-infected mice with the IFN-alpha subtypes alpha1, alpha4 or alpha9, but not alpha6 led to a significant reduction in viral loads. Decreased splenic viral load after IFN-alpha1 treatment correlated with an expansion of activated FV-specific CD8(+) T cells and NK cells into the spleen, whereas in IFN-alpha4- and -alpha9-treated mice it exclusively correlated with the activation of NK cells. The results demonstrate the distinct anti-retroviral effects of different IFN-alpha subtypes, which may be relevant for new therapeutic approaches.
Gerlach
Nicole
N
Institut für Virologie des Universitätsklinikums Essen, Universität Duisburg-Essen, Essen, Germany.
Gibbert
Kathrin
K
Alter
Christina
C
Nair
Savita
S
Zelinskyy
Gennadiy
G
James
Cassandra M
CM
Dittmer
Ulf
U
D000818:Animals; D044966:Anti-Retroviral Agents / Q000276:immunology / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D005260:Female; D005622:Friend murine leukemia virus / Q000187:drug effects* / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology* / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology; D007942:Leukemia, Experimental / Q000276:immunology; D051379:Mice; D012192:Retroviridae Infections / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology; D019562:Viral Load
D044966:Anti-Retroviral Agents; D016898:Interferon-alpha