Abstract
Reactivation of BK polyomavirus (BKPyV) infection is frequently increasing in transplant recipients treated with potent immunosuppressants and highlights the importance of immune system components in controlling viral reactivation. However, the immune response to BKPyV in general and the role of antiviral cytokines in infection control in particular are poorly understood. Here, we investigated the efficacy of interferons (IFN) alpha, lambda and gamma with regard to the BKPyV multiplication in Vero cells. Treatment with IFN-gamma inhibited the expression of the viral protein VP1 in a dose-dependent manner and decreased the expression of early and late viral transcripts. Viral inhibition by IFN-gamma was confirmed in human cells (Caki-1 cells and renal proximal tubular epithelial cells). One of the IFN-stimulated genes most strongly induced by IFN-gamma was the coding for the enzyme indoleamine 2,3 dioxygenase (IDO), which is known to limit viral replication and regulates the host immune system. The antiviral activity induced by IFN-gamma could be reversed by the addition of an IDO inhibitor, indicating that IDO has a specific role in anti-BKPyV activity. A better understanding of the action mechanism of these IFN-gamma-induced antiviral proteins might facilitate the development of novel therapeutic strategies.
Highlights
The ubiquitous BK polyomavirus (BKPyV) is involved in the development of nephropathy after kidney transplantation
BKPyV-associated nephropathy is characterized by high-level BKPyV replication in the transplanted kidney’s proximal tubular epithelial cells, which results in cell lysis and denudation of the tubular monolayer
Interferon-gamma activates the Janus kinase/signal transducer and transcription activator (JAK-STAT) pathway and allows the transcription of IFN-stimulated genes (ISGs)—many of which are involved in the fight against viral infections
Summary
The ubiquitous BK polyomavirus (BKPyV) is involved in the development of nephropathy after kidney transplantation. The pro-inflammatory cytokine IFN-gamma is the only member of the type II interferon family It is produced by innate immune cells (natural killer (NK) and antigen presenting cells) and. Interferon-gamma activates the Janus kinase/signal transducer and transcription activator (JAK-STAT) pathway and allows the transcription of IFN-stimulated genes (ISGs)—many of which are involved in the fight against viral infections. This antiviral cytokine stimulates the maturation of T and B lymphocytes and increases antibody production. Replication was inhibited by treatment with IFN-gamma [8] Viruses such as herpes simplex virus type 2 [9], measles virus [10] and vaccinia virus [11] have been found to be susceptible to the depletion tryptophan by IDO. Our results suggest that IDO has an antiviral activity on BKPyV in vitro in Caki-1 and RPTE cells
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