Impact and Regulation of Lambda Interferon Response in Human Metapneumovirus Infection

Baños-Lara, Ma. Del Rocío; Harvey, Lindsey; Mendoza, Ana; Simms, Dawn M.; Chouljenko, Vladimir N.; Wakamatsu, Nobuko; Kousoulas, Konstantin G.; Guerrero-Plata, Antonieta

doi:10.1128/jvi.02897-14

Cited by 49 publications

(71 citation statements)

References 55 publications

(93 reference statements)

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“…14 All the four studies described above have used primer sets where at least one of the primers binds to the exon/intron/exon-intron junctions (Figure 4b). Using a primer set that uniquely binds to the 3′-untranslated region of IFNL4 mRNA, IFN-λ4 induction was seen at levels similar to that of IFN-λ2/3, upon human metapneumovirus infection of A549 cells by Banos-Lara et al 45 We used the same primer set and found similar high expression levels upon poly(I:C)/HCV RNA transfection in A549 cells. 89 Two other studies have reported no such problems in amplifying IFNL4 transcripts from liver biopsies.…”

Section: Transcription Studies On the Ifnl4 Genesupporting

confidence: 59%

“…30 Some of the other IFN-λs are known to be induced by several human pathogens including M. tuberculosis, 42 human papilloma virus, 43 influenza virus 44 and human metapneumovirus (also induces IFN-λ4), 45 and have clear antiviral activities against some but not other viruses in mice (reviewed in ref. 46).…”

Section: Genetic Association Of Ifnl Locus Polymorphisms Is Not Limitmentioning

confidence: 99%

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Gene–disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections

Chinnaswamy

2016

Genes Immun

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Interferon (IFN) lambda (IFN-λ or type III IFN) gene polymorphisms were discovered in the year 2009 to have a strong association with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection in human hosts. This landmark discovery also brought renewed interest in type III IFN biology. After more than half a decade since this discovery, we now have reports that show that genetic association of IFNL gene polymorphisms in humans is not limited only to HCV infections but extends beyond, to include varied diseases such as non-alcoholic fatty liver disease, allergy and several other viral diseases including that caused by the human immunodeficiency virus. Notably, all these conditions have strong involvement of host innate immune responses. After the discovery of a deletion polymorphism that leads to the expression of a functional IFN-λ4 as the prime 'functional' variant, the relevance of other polymorphisms regulating the expression of IFN-λ3 is in doubt. Herein, I seek to critically address these issues and review the current literature to provide a framework to help further understanding of IFN-λ biology.

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Section: Transcription Studies On the Ifnl4 Genesupporting

confidence: 59%

Section: Genetic Association Of Ifnl Locus Polymorphisms Is Not Limitmentioning

confidence: 99%

Gene–disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections

Chinnaswamy

2016

Genes Immun

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“…In most studies, cultured cells were treated with IFN-λs and the impact of viral infection was assessed. These studies investigated human (66) and murine CMV (59), dengue virus (114,145), encephalomyocarditis virus (28,29,146), herpes virus type 2 (120), hepatitis B virus (115), HCV (37,60,113,115,116,147), HIV (40,117,118), human meta pneumovirus (121), influenza virus (122,(148)(149)(150)(151)(152), (128,153,154), sendai virus (155)(156)(157), and vesicular stomatitis virus (131,158,159).…”

Section: Viral Infectionsmentioning

confidence: 99%

Interferon Lambda: Modulating Immunity in Infectious Diseases

2017

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Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered. First, the IFNLR is not ubiquitously expressed: in particular, immune cells show significant variation in the expression levels of and susceptibilities to IFN-λs. Second, the binding affinities of individual IFN-λs to the IFNLR varies greatly and are generally lower compared to the binding affinities of IFN-α to its receptor. Finally, genetic variation in the form of a series of single-nucleotide polymorphisms (SNPs) linked to genes involved in the IFN-λ signaling cascade has been described and associated with the clinical course and treatment outcomes of hepatitis B and C virus infection. The clinical impact of IFN-λ signaling and the SNP variations may, however, reach far beyond viral hepatitis. Recent publications show important roles for IFN-λs in a broad range of viral infections such as human T-cell leukemia type-1 virus, rotaviruses, and influenza virus. IFN-λ also potentially modulates the course of bacterial colonization and infections as shown for Staphylococcus aureus and Mycobacterium tuberculosis. Although the immunological processes involved in controlling viral and bacterial infections are distinct, IFN-λs may interfere at various levels: as an innate immune cytokine with direct antiviral effects; or as a modulator of IFN-α-induced signaling via the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions via macrophage and dendritic cell polarization, and subsequent priming, activation, and proliferation of pathogen-specific T- and B-cells may also be important elements associated with infectious disease outcomes. This review summarizes the emerging details of the IFN-λ immunobiology in the context of the host immune response and viral and bacterial infections.

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“…This modified virus is a sensitive reporter of productive infection in live cells. Notably, hMPV both elicits and is sensitive to IFN-mediated anti-viral response [32]. As a cytolytic virus, we chose a variant of the epizootic hemorrhagic disease virus (EHDV), an orbivirus that naturally infects ruminants and is transmitted by biting midges [33].…”

Section: Introductionmentioning

confidence: 99%

Combined genetic and epigenetic interferences with interferon signaling expose prostate cancer cells to viral infection

et al. 2016

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Interferons (IFNs) induce anti-viral programs, regulate immune responses, and exert anti-proliferative effects. To escape anti-tumorigenic effects of IFNs, malignant cells attenuate JAK/STAT signaling and expression of IFN stimulated genes (ISGs). Such attenuation may enhance the susceptibility of tumor cells to oncolytic virotherapy. Here we studied genetic and epigenetic mechanisms of interference with JAK/STAT signaling and their contribution to susceptibility of prostate cancer cells to viral infection. Bioinformatics analysis of gene-expression in cohorts of prostate cancer patients revealed genetic and epigenetic interference with the IFN program. To correlate lack of IFN signaling and susceptibility to viral infection and oncolysis; we employed LNCaP prostate cancer cells as cellular model, and the human metapneumovirus and the epizootic hemorrhagic disease virus as infectious agents. In LNCaP cells, JAK1 is silenced by bi-allelic inactivating mutations and epigenetic silencing, which also silences ISGs. Chemical inhibition of epigenetic silencing partially restored IFN-sensitivity, induced low levels of expression of selected ISGs and attenuated, but failed to block, viral infection and oncolysis. Since viral infection was not blocked by epigenetic modifiers, and these compounds may independently-induce anti-tumor effects, we propose that epigenetic modifiers and virotherapy are compatible in treatment of prostate tumors defective in JAK1 expression and IFN signaling.

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Impact and Regulation of Lambda Interferon Response in Human Metapneumovirus Infection

Cited by 49 publications

References 55 publications

Gene–disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections

Gene–disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections

Interferon Lambda: Modulating Immunity in Infectious Diseases

Combined genetic and epigenetic interferences with interferon signaling expose prostate cancer cells to viral infection

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