Indoleamine 2,3-Dioxygenase Mediates Cell Type-Specific Anti-Measles Virus Activity of Gamma Interferon

Obojes, Karola; Andrés, Oliver; Kim, Kwang Sik; Däubener, Walter; Schneider‐Schaulies, Jürgen

doi:10.1128/jvi.79.12.7768-7776.2005

Cited by 79 publications

(72 citation statements)

References 65 publications

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“…Previously, it has been demonstrated that synergistic antiviral states can be induced by a variety of cytokines other than TNF and IFN-␤. For example, IL-1␤, in combination with IFN-␥, has been shown to synergistically inhibit replication of both herpes simplex virus type 1 (HSV-1) (1, 13) and measles virus (29). Importantly, our DNA microarray results indicated that IL-1␤ was upregulated 35-fold in primary human fibroblasts in response to TNF (see Table S1 in the supplemental material).…”

mentioning

confidence: 62%

The Addition of Tumor Necrosis Factor plus Beta Interferon Induces a Novel Synergistic Antiviral State against Poxviruses in Primary Human Fibroblasts

Bartee

Mohamed

López

et al. 2009

J Virol

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Tumor necrosis factor (TNF) and members of the interferon (IFN) family have been shown to independently inhibit the replication of a variety of viruses. In addition, previous reports have shown that treatment with various combinations of these antiviral cytokines induces a synergistic antiviral state that can be significantly more potent than addition of any of these cytokines alone. The mechanism of this cytokine synergy and its effects on global gene expression, however, are not well characterized. Here, we use DNA microarray analysis to demonstrate that treatment of uninfected primary human fibroblasts with TNF plus IFN-␤ induces a distinct synergistic state characterized by significant perturbations of several hundred genes which are coinduced by the individual cytokines alone, as well as the induction of more than 850 novel host cell genes. This synergy is mediated directly by the two ligands, not by intermediate secreted factors, and is necessary and sufficient to completely block the productive replication and spread of myxoma virus in human fibroblasts. In contrast, the replication of two other poxviruses, vaccinia virus and tanapox virus, are only partially inhibited in these cells by the synergistic antiviral state, whereas the spread of both of these viruses to neighboring cells was efficiently blocked. Taken together, our data indicate that the combination of TNF and IFN-␤ induces a novel synergistic antiviral state that is highly distinct from that induced by either cytokine alone.Poxviruses are large enveloped DNA viruses whose replication cycle occurs exclusively in the cytoplasm (27). Although many poxviruses are highly species specific, some members, such as monkeypox virus, tanapox virus (TPV), and cowpox virus, are able to readily leap species barriers and initiate productive zoonotic infections in humans (19,23,28,30). Myxoma virus (MV), an example of more restricted host species range, is a member of the Leporipoxvirus genus, which is uniquely restricted to rabbits (10,16,47). This host species restriction is so profound that even injection of live MV into any other vertebrate species, including humans, fails to produce a productive infection. The molecular mechanisms behind this host restriction remain largely unknown; however, there is evidence that some of the host barriers to MV permissiveness outside the rabbit are regulated by antiviral cytokines such as interferon (IFN) and tumor necrosis factor (TNF) (50, 51). The issue of restriction of MV replication in primary human cells is of particular interest because MV replicates productively in a wide variety of human cancer cells and is currently being developed as a novel oncolytic virotherapeutic to treat human cancer (46). Consequently, a better understanding of the mechanisms by which MV is restricted in primary human cells and tissues is critical before MV enters human trials.Previously, our lab has shown that primary mouse fibroblasts are nonpermissive for MV replication because they induce and secrete type I IFN in response to MV in...

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confidence: 62%

The Addition of Tumor Necrosis Factor plus Beta Interferon Induces a Novel Synergistic Antiviral State against Poxviruses in Primary Human Fibroblasts

Bartee

Mohamed

López

et al. 2009

J Virol

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“…Not surprisingly, IDO, upon induction by IFN-␥, has potent antimicrobial and antiviral activities against a variety of intracellular pathogens, including toxoplasma (10), chlamydia (8), streptococci (40), human cytomegalovirus (6), herpes simplex virus (1, 2), measles virus (48), and HIV (59). In all these cases, the antimicrobial function of IDO is mediated by tryptophan deprivation.…”

Section: Discussionmentioning

confidence: 99%

Indoleamine 2,3-Dioxygenase Mediates the Antiviral Effect of Gamma Interferon against Hepatitis B Virus in Human Hepatocyte-Derived Cells

Mao

Zhang

Jiang

et al. 2011

J Virol

109

100

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Alpha interferon (IFN-␣) is an approved medication for chronic hepatitis B. Gamma interferon (IFN-␥) is a key mediator of host innate and adaptive antiviral immunity against hepatitis B virus (HBV) infection in vivo.In an effort to elucidate the antiviral mechanism of these cytokines, 37 IFN-stimulated genes (ISGs), which are highly inducible in hepatocytes, were tested for their ability to inhibit HBV replication upon overexpression in human hepatoma cells. One ISG candidate, indoleamine 2,3-dioxygenase (IDO), an IFN-␥-induced enzyme catalyzing tryptophan degradation, efficiently reduced the level of intracellular HBV DNA without altering the steady-state level of viral RNA. Furthermore, expression of an enzymatically inactive IDO mutant did not inhibit HBV replication, and tryptophan supplementation in culture completely restored HBV replication in IDO-expressing cells, indicating that the antiviral effect elicited by IDO is mediated by tryptophan deprivation. Interestingly, IDO-mediated tryptophan deprivation preferentially inhibited viral protein translation and genome replication but did not significantly alter global cellular protein synthesis. Finally, tryptophan supplementation was able to completely restore HBV replication in IFN-␥-but not IFN-␣-treated cells, which strongly argues that IDO is the primary mediator of IFN-␥-elicited antiviral response against HBV in human hepatocyte-derived cells.Hepatitis B virus (HBV) is a hepatotropic virus in the family of Hepadnaviridae (18, 56) which has infected two billion people worldwide. Although most infected adults can resolve the infection, approximately 5 to 10% of adulthood infections and more than 90% of neonatal infections become lifelong persistent, which causes a significant public health burden currently affecting more than 350 million individuals worldwide (36,41). Patients with chronic hepatitis B carry a high risk of cirrhosis and primary hepatocellular carcinoma (5, 36).It is generally believed that the outcomes of HBV infection and disease pathogenesis are primarily determined by the host adaptive antiviral immune response (9). The resolution of HBV infection is associated with a robust, polyclonal viral antigen-specific cytotoxic T lymphocyte (CTL) response that kills and/or noncytopathically cures virally infected hepatocytes. The latter effect is primarily mediated by inflammatory cytokines, including gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣) (17,18,20,21). Interestingly, although it has been shown that HBV can evade host innate immunity surveillance, as evidenced by its failure to induce the expression of interferon-stimulated genes (ISGs) in the liver of chimpanzees during the early phase of infection (66), the virus is sensitive to IFN-␣/␤-induced antiviral response in transgenic mice and in people (30,49). For example, treatment of chronic hepatitis B with pegylated IFN-␣ for 48 weeks can achieve sustained virological response in 30 to 40% of the treated patients (29).In efforts to elucidate the antiviral mechanism ...

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“…IDO-sensitive organisms include intracellular facultative parasites such as Toxoplasma gondii, as well as certain bacteria whose replication can be inhibited by depletion of the rare essential amino acid tryptophan by the action of IDO (15,52). In addition, IDO appears to account for IFN-␥-mediated antiviral activity against human cytomegalovirus (HCMV), herpes simplex virus, and measles virus (2,6,58).…”

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confidence: 99%

Astrocyte Indoleamine 2,3-Dioxygenase Is Induced by the TLR3 Ligand Poly(I:C): Mechanism of Induction and Role in Antiviral Response

Suh

Zhao

Rivieccio

et al. 2007

J Virol

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Indoleamine 2,3-Dioxygenase Mediates Cell Type-Specific Anti-Measles Virus Activity of Gamma Interferon

Abstract: Gamma interferon (IFN-␥

Cited by 79 publications

References 65 publications

The Addition of Tumor Necrosis Factor plus Beta Interferon Induces a Novel Synergistic Antiviral State against Poxviruses in Primary Human Fibroblasts

The Addition of Tumor Necrosis Factor plus Beta Interferon Induces a Novel Synergistic Antiviral State against Poxviruses in Primary Human Fibroblasts

Indoleamine 2,3-Dioxygenase Mediates the Antiviral Effect of Gamma Interferon against Hepatitis B Virus in Human Hepatocyte-Derived Cells

Astrocyte Indoleamine 2,3-Dioxygenase Is Induced by the TLR3 Ligand Poly(I:C): Mechanism of Induction and Role in Antiviral Response

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