Anti‐retroviral effects of type I IFN subtypes in vivo

Abstract

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-a subtypes but the biological functions of IFN-a subtypes in retroviral infections are unknown. We have used the Friend retrovirus model to determine the anti-viral effects of IFN-a subtypes in vitro and in vivo. IFN-a subtypes a1, a4, a6 or a9 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-a subtypes a1, a4 or a9, but not a6 led to a significant reduction in viral loads. Decreased splenic viral load after IFN-a1 treatment correlated with an expansion of activated FV-specific CD8 1 T cells and NK cells into the spleen, whereas in IFN-a4-and -a9-treated mice it exclusively correlated with the activation of NK cells. The results demonstrate the distinct anti-retroviral effects of different IFN-a subtypes, which may be relevant for new therapeutic approaches.

Antiviral Activities of Different Interferon Types and Subtypes against Hepatitis E Virus Replication

“…By using a subgenomic genotype 2a replicon system, we observed high susceptibility of HCV for all subtypes with no distinction for IFN-␣17, which could be due to the different experimental setup and viral constructs. For herpes simplex virus (HSV), it was shown that the murine IFN-␣ homologs 1, 4, 5, 6, and 9 were inhibiting viral replication (37) and in a Friend virus in vivo infection model, therapeutic application with murine IFN-␣1, -4, -9, and -11 was able to reduce viral loads significantly in contrast to IFN-␣2, -5, and -6 (38,39). HEV replication could be efficiently blocked by ribavirin treatment and a significant benefit of a combination of any IFN-␣ subtype with ribavirin could not be observed using one constant ribavirin dose of 25 M (Fig.…”

Polyinosinic-Polycytidylic Acid Treatment of Friend Retrovirus-Infected Mice Improves Functional Properties of Virus-Specific T Cells and Prevents Virus-Induced Disease

“…However, other IFN-a subtypes, such as 4 and 9, were also effective in reducing FV loads but did not increase absolute numbers of virus-specific CD8 + T cells (67). The most predominant IFN-a subtype that is produced after poly(I:C) treatment in vivo is IFN-a5 (data not shown), but the influence of this particular subtype on CD8 + T cell activity during FV infection has not been investigated so far.…”

Interferon Alpha Subtype-Specific Suppression of HIV-1 InfectionIn Vivo

“…Additionally, evolutionary selection of multiple functional IFN-␣ subtypes indicates that each subtype has essential and nonredundant functions (6). Evidence of this includes studies in the Friend retrovirus (FV) model, which showed that treatment with distinct IFN-␣ subtypes induced specific downstream responses that effectively controlled FV infections, whereas other subtypes induced responses that were ineffective (7,8). Furthermore, murine herpesvirus or influenza virus infections were controlled by different subtypes than those inhibiting FV (9)(10)(11)(12)(13).…”