Respiratory syncytial virus induces indoleamine 2,3‐dioxygenase activity: a potential novel role in the development of allergic disease

Ajamian, Farnam; Wu, Yingqi; Ebeling, Cory; Ilarraza, Ramses; Odemuyiwa, Solomon O.; Moqbel, Redwan; Adamko, Darryl J.

doi:10.1111/cea.12498

Cited by 25 publications

(31 citation statements)

References 89 publications

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“…Similar to our findings with lung epithelial A549 cells, in neuronal cells IFN-␥ strongly induced IDO expression, causing inhibition of HSV replication, which could be rescued by Trp (54). Interaction of IDO with several other viruses, such as HIV, cytomegalovirus, RSV, hepatitis virus, and influenza A virus, has been unraveled recently, but mainly in the context of T cell responses and induced immunity (52,(55)(56)(57)(58). The effect of IDO on PIV3, however, was appreciated in nonimmune cells; it is thus representative of a cellintrinsic mechanism that directly inhibits viral gene expression.…”

Section: Discussionsupporting

confidence: 86%

Identification of Interferon-Stimulated Gene Proteins That Inhibit Human Parainfluenza Virus Type 3

Rabbani

Ribaudo

Guo

et al. 2016

J Virol

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A major arm of cellular innate immunity is type I interferon (IFN), represented by IFN-␣ and IFN-␤. Type I IFN transcriptionally induces a large number of cellular genes, collectively known as IFN-stimulated gene (ISG) proteins, which act as antivirals. The IFIT (interferon-induced proteins with tetratricopeptide repeats) family proteins constitute a major subclass of ISG proteins and are characterized by multiple tetratricopeptide repeats (TPRs). In this study, we have interrogated IFIT proteins for the ability to inhibit the growth of human parainfluenza virus type 3 (PIV3), a nonsegmented negative-strand RNA virus of the Paramyxoviridae family and a major cause of respiratory disease in children. We found that IFIT1 significantly inhibited PIV3, whereas IFIT2, IFIT3, and IFIT5 were less effective or not at all. In further screening a set of ISG proteins we discovered that several other such proteins also inhibited PIV3, including IFITM1, IDO (indoleamine 2,3-dioxygenase), PKR (protein kinase, RNA activated), and viperin (virus inhibitory protein, endoplasmic reticulum associated, interferon inducible)/Cig5. The antiviral effect of IDO, the enzyme that catalyzes the first step of tryptophan degradation, could be counteracted by tryptophan. These results advance our knowledge of diverse ISG proteins functioning as antivirals and may provide novel approaches against PIV3. IMPORTANCE The innate immunity of the host, typified by interferon (IFN), is a major antiviral defense. IFN inhibits virus growth by inducing a large number of IFN-stimulated gene (ISG) proteins, several of which have been shown to have specific antiviral functions.Parainfluenza virus type 3 (PIV3) is major pathogen of children, and no reliable vaccine or specific antiviral against it currently exists. In this article, we report several ISG proteins that strongly inhibit PIV3 growth, the use of which may allow a better antiviral regimen targeting PIV3. P arainfluenza virus type 3 (PIV3) is a nonsegmented, negativestrand RNA virus belonging to the Paramyxoviridae family and a major cause of lower respiratory tract infection in humans and cattle (1-3). Human PIV3 is a particularly serious pathogen in young children, second in clinic importance only to respiratory syncytial virus (RSV), another member of the same family (3). There is currently no specific treatment or approved vaccine for PIV3. However, RNA viruses in general, and paramyxoviruses in particular, induce type I interferon (IFN), a major arm of host innate immunity, mainly by activating a cytoplasmic RNA helicase of the RIG-I family, which is followed by a signaling cascade ultimately leading to transcriptional induction of IFN genes (4-6). Early reports showed that PIV3 is highly sensitive to IFN (7), suggesting that this natural antiviral mechanism holds the potential to be harnessed. Type I IFN by itself has no antiviral activity, but upon binding to its cognate receptor on the cell surface, it triggers the so-called IFN response pathway, in which transcription factors STAT...

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Section: Discussionsupporting

confidence: 86%

Identification of Interferon-Stimulated Gene Proteins That Inhibit Human Parainfluenza Virus Type 3

Rabbani

Ribaudo

Guo

et al. 2016

J Virol

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“…IDO is distributed mainly in dendritic cells and certain tumour cells. It has also been demonstrated that IDO is significantly increased in certain viral pathophysiological conditions . Although few IDO + cells were found in normal skin epithelium, they were abundantly expressed in wart tissue.…”

Section: Discussionmentioning

confidence: 98%

“…It has also been demonstrated that IDO is significantly increased in certain viral pathophysiological conditions. 27,28 Although few IDO + cells were found in normal skin epithelium, they were abundantly expressed in wart tissue. It is interesting that the wart IDO was derived mainly from the epidermal cells of the warts rather than the LCs.…”

Section: Discussionmentioning

confidence: 99%

Immunotolerant indoleamine‐2,3‐dioxygenase is increased in condyloma acuminata

et al. 2017

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“…Recent reports show that RSV induces Indoleamine-2,3-dioxygenase (IDO) in dendritic cells (DCs) [11] and Mesenchymal Stromal Cells (MSCs) [12] and there is a direct correlation between RSV replication and IDO expression [11]. Since IDO is an immunomodulatory enzyme that has been shown to affect a number of immune responses including some linked to RSV [11,12], it might participate in the pathogenesis of RSV disease. IDO catalyzes the degradation of the essential amino acid L-tryptophan and generates a family of catabolites known as kynurenines.…”

Section: Introductionmentioning

confidence: 99%

Protective role of Indoleamine 2,3 dioxygenase in Respiratory Syncytial Virus associated immune response in airway epithelial cells

et al. 2017

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RSV is a major cause of severe lower respiratory infection in infants and young children. With no vaccine yet available, it is important to clarify mechanisms of disease pathogenesis. Since indoleamine-2,3-dioxygenase (IDO) is an immunomodulatory enzyme and is upregulated with RSV infection, we studied it in vivo during infection of BALB/c mice and in vitro in A549 cells. RSV infection upregulated IDO transcripts in vivo and in vitro. IDO siRNA decreased IDO transcripts ~2 fold compared to control siRNA after RSV infection but this decrease did not affect RSV replication. In the presence of IFN-γ, siRNA-induced decrease in IDO expression was associated with an increase in virus replication and increased levels of IL-6, IL-8, CXCL10 and CCL4. Thus, our results show IDO is upregulated with RSV infection and this upregulation likely participates with IFN-γ in inhibition of virus replication and suppression of some host cell responses to infection.

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Respiratory syncytial virus induces indoleamine 2,3‐dioxygenase activity: a potential novel role in the development of allergic disease

Abstract: Our data show for the first time that RSV can induce the expression and bioactivity of IDO in human moDC, in a virus replication-dependant fashion. We suggest that RSV activation of IDO could be a potential mechanism for the development of allergic diseases.

Cited by 25 publications

References 89 publications

Identification of Interferon-Stimulated Gene Proteins That Inhibit Human Parainfluenza Virus Type 3

Identification of Interferon-Stimulated Gene Proteins That Inhibit Human Parainfluenza Virus Type 3

Immunotolerant indoleamine‐2,3‐dioxygenase is increased in condyloma acuminata

Protective role of Indoleamine 2,3 dioxygenase in Respiratory Syncytial Virus associated immune response in airway epithelial cells

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