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.

SARS-CoV-2 sensitive to type I interferon pretreatment.

Abstract: SARS-CoV-2, a novel coronavirus (CoV), has recently emerged causing an ongoing outbreak of viral pneumonia around the world. While genetically distinct from the original SARS-CoV, both group 2B CoVs share similar genome organization and origins to coronaviruses harbored in bats. Importantly, initial guidance has used insights from SARS-CoV infection to inform treatment and public health strategies. In this report, we evaluate type-I Interferon (IFN-I) sensitivity of SARS-CoV-2 relative to the original SARS-CoV. Our results indicate that while SARS-CoV-2 maintains similar viral replication kinetics to SARS-CoV in Vero cell, the novel CoV is much more sensitive to IFN-I pretreatment. Examining transcriptional factor activation and interferon stimulated gene (ISG) induction, SARS-CoV-2 in the context of type I IFN induces phosphorylation of STAT1 and increased ISG proteins. In contrast, the original SARS-CoV has no evidence for STAT1 phosphorylation or ISG protein increases even in the presence of type I IFN pretreatment. Finally, we examined homology between SARS-CoV and SARS-CoV-2 in viral proteins shown to be interferon antagonist. The absence of open reading frame (ORF) 3b and significant changes to ORF6 suggest the two key IFN antagonists may not maintain equivalent function in SARS-CoV-2. Together, the results identify key differences in susceptibility to the IFN-I response between SARS-CoV and SARS-CoV-2. that could help inform disease progression, treatment options, and animal model development. Importance With the ongoing outbreak of COVID-19 disease, differences between the SARS-CoV-2 and the original SARS-CoV could be leveraged to inform disease progression and eventual treatment options. In addition, these findings could have key implications for animal model development as well as further research into how SARS-CoV-2 modulates the type I IFN response early during infection. Article Summary SARS-CoV-2 has similar replication kinetics to SARS-CoV, but demonstrates significant sensitivity to type I interferon treatment.

Impaired interferon signaling is a common immune defect in human cancer

Abstract: Immune dysfunction develops in patients with many cancer types and may contribute to tumor progression and failure of immunotherapy. Mechanisms underlying cancer-associated immune dysfunction are not fully understood. Efficient IFN signaling is critical to lymphocyte function; animals rendered deficient in IFN signaling develop cancer at higher rates. We hypothesized that altered IFN signaling may be a key mechanism of immune dysfunction common to cancer. To address this, we assessed the functional responses to IFN in peripheral blood lymphocytes from patients with 3 major cancers: breast cancer, melanoma, and gastrointestinal cancer. Type-I IFN (IFN-α)-induced signaling was reduced in T cells and B cells from all 3 cancer-patient groups compared to healthy controls. Type-II IFN (IFN-γ)-induced signaling was reduced in B cells from all 3 cancer patient groups, but not in T cells or natural killer cells. Impaired-IFN signaling was equally evident in stage II, III, and IV breast cancer patients, and downstream functional defects in T cell activation were identified. Taken together, these findings indicate that defects in lymphocyte IFN signaling arise in patients with breast cancer, melanoma, and gastrointestinal cancer, and these defects may represent a common cancer-associated mechanism of immune dysfunction.

Natural occurrence of 2-5A in interferon-treated EMC virus-infected L cells

Abstract: Until now the inierfer on-mediated 2′–5′ adenine oligonucleotide inhibitors (2–5A) of cell-free protein synthesis have not been detected in intact cells. Here we report their natural occurrence in interferon-treated, EMC virus-infected mouse L cells in amounts consistent with the idea that they play a part in the inhibition of virus growth.

IFN‐α/β enhances BCR‐dependent B cell responses

Abstract: Type I interferon (IFN-I) is constitutively produced in the bone marrow (BM), and induced at sites of inflammation and following infection by viruses or microorganisms. We have previously shown that IFN-I regulates the generation and selection of normal B cell populations in the BM. In the present work, we assess the effects of IFN-I on mature B cell function by monitoring the responses of IFN-a/b-treated murine splenic B cells to apoptotic, mitogenic and activating stimuli. A similar analysis is performed on BM mature B cells obtained from wild-type or IFN-I receptor-deficient mice. IFN-a/b is shown to induce B cells to a state of partial activation characterized by the upregulation of CD69, CD86 and CD25 molecules in the absence of either proliferation or terminal differentiation. B cells treated with IFN-a/b show an increased survival and resistance to Fasmediated apoptosis. IFN-a/b also enhances B cell responses to BCR ligation such as calcium fluxes, IgM internalization, induction of activation markers and proliferation. These results indicate that in addition to its inhibitory effect on viral replication and T cell apoptosis, IFN-a/b plays an essential role during an inflammatory response by lowering the threshold for B cell induction, thereby promoting fast and polyclonal antibody responses.