Viruses and interferon: a fight for supremacy

Katze, Michael G.; He, Yiping; Gale, Michael

doi:10.1038/nri888

Cited by 1,137 publications

(952 citation statements)

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Section: Discussionmentioning

confidence: 99%

“…Viruses have evolved multiple mechanisms to neutralize the activity of host defenses, including IFN [15,16]. For example, myxoma virus has been shown to secrete a homolog of the IFN-c receptor, which inhibits the biological activity of extracellular IFN-c [17].…”

Section: Introductionmentioning

confidence: 99%

“…Their expression can be induced on other cells types after stimulation with cytokines such as IFN-c. IFN-c-induced MHC class II expression requires the Jak/ Stat pathway and the CIITA expression at a downstream step. CIITA is the general regulator of MHC class II gene expression, both constitutive and inducible, and it is likely to function as a transcriptional coactivator interacting with ubiquitous DNAbinding proteins at an MHC class II promoter [13,14].Viruses have evolved multiple mechanisms to neutralize the activity of host defenses, including IFN [15,16]. For example, myxoma virus has been shown to secrete a homolog of the IFN-c receptor, which inhibits the biological activity of extracellular .…”

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confidence: 99%

“…Cytomegalovirus also down-regulates IFN-c-induced expression of MHC class II molecules by inhibiting Stat1 phosphorylation and CIITA expression in different cell lines [22]. In the course of evolution, influenza A viruses have also developed different mechanisms to counteract the IFN-induced antiviral activities [3,15,23]. The influenza-virus-encoded nonstructural protein 1 (NS1), which binds dsRNA and forms dimers in vivo, has been shown to inhibit the host cell antiviral response by multiple mechanisms.…”

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confidence: 99%

“…Innate cytokine responses, such as IFN-a/b and IFN-c, can have roles in determining the rate of virus replication in the initial stages of infection and in shaping the initial inflammatory and downstream adaptive immune responses [10,11]. In turn, viruses have evolved sophisticated mechanisms to subvert host immune responses and support efficient viral replication [15,16].Influenza A virus infection causes significant morbidity and mortality in human populations worldwide, making the understanding of disease mechanisms and immunity to this pathogen of great importance. Influenza A viruses have evolved strategies to ensure their survival in the host [3,23].…”

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Influenza A virus abrogates IFN‐γ response in respiratory epithelial cells by disruption of the Jak/Stat pathway

et al. 2008

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The innate immunity to viral infections induces a potent antiviral response mediated by interferons (IFN). Although IFN-c is detected during the acute stages of illness in the upper respiratory tract secretions and in the serum of influenza A virus-infected individuals, control of influenza A virus is not dependent upon IFN-c as evidenced by studies using anti-IFN-c Ab and IFN-c -/-mice. Thus, we hypothesized that IFN-c is not critical in host survival because influenza A virus has mechanisms to evade the antiviral activity of IFN-c. To test this, A549 cells, an epithelial cell line derived from lung adenocarcinoma, were infected with influenza virus strain A/Aichi/2/68 (H3N2) (Aichi) and/or stimulated with IFN-c to detect IFN-c-stimulated MHC class II expression. Influenza A virus infection inhibited IFN-c-induced up-regulation of HLA-DRa mRNA and the IFN-c induction of class II transactivator (CIITA), an obligate mediator of MHC class II expression. Nuclear translocation of Stat1a upon IFN-c stimulation was significantly inhibited in influenza A virus-infected cells and this was associated with a decrease in Tyr701 and Ser727 phosphorylation of Stat1a. Thus, influenza A virus subverts antiviral host defense mediated by IFN-c through effects on the intracellular signaling pathways. IntroductionInfluenza A viruses are negative-strand RNA viruses that have a segmented genome with a coding capacity for 11 polypeptides. The virus genome is composed of eight different RNA segments, which are tightly associated with the viral nucleoprotein and polymerases in ribonucleoprotein complexes [1]. Influenza A viruses, causing acute infections, continuously escape from recognition by virus neutralizing Ab as a result of accumulation of mutations in their surface glycoproteins hemagglutinin and neuraminidase (antigenic drift) or by introduction of new subtypes of these glycoproteins (antigenic shift) [2,3]. Recent outbreaks of highly pathogenic avian influenza A virus infections in poultry and in humans have raised concerns that a new influenza pandemic will occur in the near future [4]. Thus, prediction of the severity of continuously emerging human influenza virus strains remains a high public health priority, but it is limited by our incomplete understanding of the molecular determinants of pathogenicity in this disease. Although factors dictating the severity of virus disease are complex, interaction between inherent viral properties and host cellular response ultimately determines disease outcome. The first site of viral contact with the host and main target of infection and inflammation is the airway mucosal epithelium. Epithelial cells at the airway mucosal surface have a variety of inflammatory and immune defense mechanisms to deal with virus, including Eur. J. Immunol. 2008. 38: 1559-1573 Immunity to infection expression of cytokines with chemoattractant and proinflammatory functions [5], intercellular adhesion molecule-1 (ICAM-1) [6], IFN regulatory factor 1 (IRF-1) [7], nitric oxide synthase 2 (NOS2) [8], and MHC ...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Influenza A virus abrogates IFN‐γ response in respiratory epithelial cells by disruption of the Jak/Stat pathway

et al. 2008

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Targeted Identification of Infection‐Related HLA Class I–Presented Epitopes by Stable Isotope Tagging of Epitopes (SITE)

Meiring¹,

Soethout²,

Jong³

et al. 2007

CP in Immunology

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Identification of peptides presented in human leukocyte antigen (HLA) class I molecules after viral infection is of strategic importance for immunology and vaccine development. A powerful strategy aimed at the rapid, unambiguous identification of naturally processed HLA class I-associated peptides, which are induced by viral infection, is presented here. The methodology, stable isotope tagging of epitopes (SITE), is based on metabolic labeling of endogenously synthesized proteins during infection. This is accomplished by culturing virus-infected cells with stable isotope-labeled amino acids that are expected to be anchor residues for the human leukocyte antigen allele of interest. Subsequently, these cells are mixed with an equal number of noninfected cells, which are cultured in normal medium. Finally, peptides are acid-eluted from immunoprecipitated HLA molecules and subjected to two-dimensional nanoscale liquid chromatography-mass spectrometry analysis. Virus-induced peptides are identified through computer-assisted detection of characteristic, binomially distributed ratios of labeled and unlabeled molecules.

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