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Interferon

About: Interferon is a research topic. Over the lifetime, 28969 publications have been published within this topic receiving 1219645 citations. The topic is also known as: IFN & interferons.


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Journal ArticleDOI
TL;DR: The anti-interferon function of PB1-F2 is characterized and it is suggested that this activity contributes to the enhanced pathogenicity seen with PB1/Puerto Rico/8/1934- expressing influenza viruses.
Abstract: PB1-F2 is a 90 amino acid protein that is expressed from the +1 open reading frame in the PB1 gene of some influenza A viruses and has been shown to contribute to viral pathogenicity. Notably, a serine at position 66 (66S) in PB1-F2 is known to increase virulence compared to an isogenic virus with an asparagine (66N) at this position. Recently, we found that an influenza virus expressing PB1-F2 N66S suppresses interferon (IFN)-stimulated genes in mice. To characterize this phenomenon, we employed several in vitro assays. Overexpression of the A/Puerto Rico/8/1934 (PR8) PB1-F2 protein in 293T cells decreased RIG-I mediated activation of an IFN-β reporter and secretion of IFN as determined by bioassay. Of note, the PB1-F2 N66S protein showed enhanced IFN antagonism activity compared to PB1-F2 wildtype. Similar observations were found in the context of viral infection with a PR8 PB1-F2 N66S virus. To understand the relationship between NS1, a previously described influenza virus protein involved in suppression of IFN synthesis, and PB1-F2, we investigated the induction of IFN when NS1 and PB1-F2 were co-expressed in an in vitro transfection system. In this assay we found that PB1-F2 N66S further reduced IFN induction in the presence of NS1. By inducing the IFN-β reporter at different levels in the signaling cascade, we found that PB1-F2 inhibited IFN production at the level of the mitochondrial antiviral signaling protein (MAVS). Furthermore, immunofluorescence studies revealed that PB1-F2 co-localizes with MAVS. In summary, we have characterized the anti-interferon function of PB1-F2 and we suggest that this activity contributes to the enhanced pathogenicity seen with PB1-F2 N66S- expressing influenza viruses.

218 citations

Journal ArticleDOI
TL;DR: The data indicate that Silymarin exerts anti-inflammatory and antiviral effects, and suggest that complementary and alternative medicine-based approaches may assist in the management of patients with chronic hepatitis C.

217 citations

Journal ArticleDOI
TL;DR: The DNA inhibitor studies indicate that immune interferon synthesis occurs maximally in association with at least some proliferative response and that submaximal levels ofinterferon production occur in mitogen-treated cultures in the absence of detectable proliferation.
Abstract: The mitogenicity, ability to induce immune interferon, and relationship between interferon synthesis and cell proliferative response were studied using human peripheral lymphocytes stimulated by staphylococcal enterotoxin A (SEA), phytohemagglutinin-P (PHA-P), and concanavalin A (ConA) Maximum cell proliferative responses ([(3)H]thymidine incorporation) and protein synthesis ((14)C-amino acid incorporation) occurred on days 3 and 4, respectively, after stimulation by each of the three mitogens Maximal immune interferon levels were found 3 or 4 days after mitogen stimulation SEA-treated cultures produced approximately three times more interferon than did cultures stimulated with PHA-P or ConA Furthermore, SEA stimulated maximal cell proliferation over a much broader concentration range than did PHA-P and ConA (SEA, 10(-5) to 10(2) mug/ml; PHA-P, 10(1) to 10(2) mug/ml; ConA, 10(1) to 10(15) mug/ml) Interferon was also produced at maximal or near maximal levels over a broad concentration range of SEA (10(-2) to 10(2) mug/ml) Also, we found that inhibition of mitogen-induced DNA and protein synthesis to control levels by mitomycin C or cytosine arabinoside partially reduced interferon production The DNA inhibitor studies indicate that immune interferon synthesis occurs maximally in association with at least some proliferative response and that submaximal levels of interferon production occur in mitogen-treated cultures in the absence of detectable proliferation The ability of SEA to stimulate maximal DNA and immune interferon synthesis at concentrations of 35 x 10(-13) M and 35 x 10(-10) M, respectively, puts it in a potency range similar to that of hormones Thus, SEA may play an important role in gut immunity and Staphylococcus aureus infections at concentrations well below those required for emetic effects

217 citations

Journal ArticleDOI
01 Jun 2006-Brain
TL;DR: It is suggested that the accumulation of highly antigen-sensitive EBNA1-specific Th1 cells in multiple sclerosis is capable of sustaining autoimmunity by cross-recognition of autoantigens or by TCR-independent bystander mechanisms.
Abstract: * These senior authors contributed equally to this work. Epidemiological studies consistently demonstrate that patients with multiple sclerosis are almost universally infected with Epstein–Barr virus (EBV) and that the risk of developing the disease increases with the level of EBV-specific antibody titers. The EBV-encoded nuclear antigen-1 (EBNA1) maintains the viral episome in replicating infected human B cells, and EBNA1-specific CD4 + T cells have been identified as a crucial part of the EBV-specific immune control in healthy individuals. We studied 20 untreated EBV seropositive patients with multiple sclerosis and 20 healthy EBV carriers matched demographically and for the expression of multiple sclerosis-associated HLA-DR alleles for their immunological control of EBV latency at the level of EBNA1-specific T cells. Using 51 overlapping peptides covering the C-terminal of EBNA1 domain of EBNA1 (amino acids 400–641), peptide-specific CD4 + memory T cells in patients with multiple sclerosis were found to be strikingly elevated in frequency, showed increased proliferative capacity and an enhanced interferon-g production. In contrast to EBNA1, T-cell responses to three other latent and three other lytic immunodominant EBV antigens and human cytomegalovirus (HCMV) epitopes did not differ between patients and controls, indicating a distinct role for EBNA1-specific T-cell responses in multiple sclerosis. CD4 + T cells from healthy virus carriers preferentially recognized multiple epitopes within the centre part of the C-terminal, whereas the stimulatory epitopes in multiple sclerosis patients covered the entire sequence of this domain of EBNA1. Quantification of EBV viral loads in peripheral blood mononuclear cells (PBMC) by real-time polymerase chain reaction (PCR) showed higher levels of EBV copy numbers in some patients with multiple sclerosis, although the overall difference in viral loads was not statistically significant compared with healthy virus carriers. We suggest that the accumulation of highly antigen-sensitive EBNA1-specific Th1 cells in multiple sclerosis is capable of sustaining autoimmunity by cross-recognition of autoantigens or by TCR-independent bystander mechanisms.

217 citations

Journal ArticleDOI
TL;DR: It is demonstrated that IFN-γ is essential for control of chronic vascular pathology induced by γHV68 and suggested γ-herpesviruses as candidate etiologic agents for human vasculitis.
Abstract: Murine γ-herpesvirus 68 causes severe large-vessel arteritis in mice lacking interferon-γ responsiveness: A new model for virus-induced vascular disease

217 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023812
20221,354
20211,152
20201,057
2019902
2018881