Reactogenicity of BNT162b2 mRNA COVID-19 Vaccine in a Young Working Age Population: A Survey among Medical School Residents, within a Mass Vaccination Campaign, in a Regional Reference Teaching Hospital in Italy.

Vaccinations are a key prevention measure in fighting the COVID-19 pandemic. The BNT162b2 mRNA vaccine (BioNTech/Pfizer), the first to receive authorization, was widely used in the mass vaccination campaign in Italy. Healthcare workers were identified as a priority group for vaccination, but few studies have assessed its reactogenicity among the young working age population.

IκB kinase-ε-mediated phosphorylation triggers IRF-1 degradation in breast cancer cells.

Interferon Regulatory Factors (IRFs) are key regulators of immunity, cell survival and apoptosis. IRF transcriptional activity and subcellular localization are tightly regulated by posttranscriptional modifications including phosphorylation. The IκB kinase family member IKK-ε is essential in regulating antiviral innate immunity mediated by IRFs but is now also recognized as an oncoprotein amplified and overexpressed in breast cancer cell lines and patient-derived tumors.

A model of the three-dimensional structure of human interferon responsive factor 1 and its modifications upon phosphorylation or phosphorylation-mimicking mutations.

Interferon responsive factor 1 (IRF-1) is a pleiotropic transcription factor, possessing non-redundant biological activities that depend on its interaction with different protein partners and multiple post-translational modifications including phosphorylation. In particular, a 5'-SXXXSXS-3' motif of the protein represents the target of the IB-related kinases, TANK-binding kinase (TBK)-1 and inhibitor of nuclear factor kappa-B kinase (IKK)-ε. Here, a 3D model of human IRF-1 was determined by using multi-template comparative modeling and molecular dynamics approaches.

Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide.

The antitumor effectiveness of cyclophosphamide (CTX) and other chemotherapeutics was shown to rely not only on direct cytotoxicity but also on immunogenic tumor cell death and systemic immunomodulatory mechanisms, including regulatory T cell (Treg) depletion, Th1 cell polarization, type I interferon (IFN) and proinflammatory cytokine production. IFN regulatory factor (IRF)-1 is a transcriptional regulator of IFNs and IFN-inducible genes, involved in the control of Th1 and Treg differentiation and in sterile inflammation. Aim of this study was to explore the role of IRF-1 in CTX-induced antitumor effects and related immune activities.

HIV-1 Tat Recruits HDM2 E3 Ligase To Target IRF-1 for Ubiquitination and Proteasomal Degradation.

Unlabelled: In addition to its ability to regulate HIV-1 promoter activation, the viral transactivator Tat also functions as a determinant of pathogenesis and disease progression by directly and indirectly modulating the host anti-HIV response, largely through the capacity of Tat to interact with and modulate the activities of multiple host proteins. We previously demonstrated that Tat modulated both viral and host transcriptional machinery by interacting with the cellular transcription factor interferon regulatory factor 1 (IRF-1). In the present study, we investigated the mechanistic basis and functional significance of Tat-IRF-1 interaction and demonstrate that Tat dramatically decreased IRF-1 protein stability.

IFN Regulatory Factors and Antiviral Innate Immunity: How Viruses Can Get Better.

The interferon regulatory factor (IRF) family consists of transcriptional regulators that exert multifaceted and versatile functions in multiple biological processes. Their crucial role as central mediators in the establishment and execution of host immunity in response to pathogen-derived signals downstream pattern recognition receptors (PRRs) makes IRFs a hallmark of the host antiviral response. They function as hub molecules at the crossroad of different signaling pathways for the induction of interferon (IFN) and inflammatory cytokines, as well as of antiviral and immunomodulatory genes even in an IFN-independent manner.

Early IFN type I response: Learning from microbial evasion strategies.

Type I interferon (IFN) comprises a class of cytokines first discovered more than 50 years ago and initially characterized for their ability to interfere with viral replication and restrict locally viral propagation. As such, their induction downstream of germ-line encoded pattern recognition receptors (PRRs) upon recognition of pathogen-associated molecular patterns (PAMPs) is a hallmark of the host antiviral response. The acknowledgment that several PAMPs, not just of viral origin, may induce IFN, pinpoints at these molecules as a first line of host defense against a number of invading pathogens.

Influenza vaccination among healthcare workers in Italy.

Influenza vaccination is a fundamental tool for the prevention of influenza in healthcare settings and its administration to healthcare workers (HCWs) is recommended in more than 40 countries including United States of America and many countries of the European Union. Despite these recommendations, the compliance of HCWs to influenza vaccination is largely inadequate in Italy. Since 2005/06 season, a comprehensive multifaceted intervention project aimed at increasing the seasonal influenza vaccination coverage rates among HCWs was performed at the IRCCS AOU San Martino IST teaching hospital in Genoa, Italy, the regional tertiary adult acute-care reference center with a 1300 bed capacity.

Type I IFN--a blunt spear in fighting HIV-1 infection.

For more than 50 years, Type I Interferon (IFN) has been recognized as critical in controlling viral infections. IFN is produced downstream germ-line encoded pattern recognition receptors (PRRs) upon engagement by pathogen-associated molecular patterns (PAMPs). As a result, hundreds of different interferon-stimulated genes (ISGs) are rapidly induced, acting in both autocrine and paracrine manner to build a barrier against viral replication and spread.

HIV-1 latency: an update of molecular mechanisms and therapeutic strategies.

The major obstacle towards HIV-1 eradication is the life-long persistence of the virus in reservoirs of latently infected cells. In these cells the proviral DNA is integrated in the host's genome but it does not actively replicate, becoming invisible to the host immune system and unaffected by existing antiviral drugs. Rebound of viremia and recovery of systemic infection that follows interruption of therapy, necessitates life-long treatments with problems of compliance, toxicity, and untenable costs, especially in developing countries where the infection hits worst.

IκB kinase ε targets interferon regulatory factor 1 in activated T lymphocytes.

IκB kinase ε (IKK-ε) has an essential role as a regulator of innate immunity, functioning downstream of pattern recognition receptors to modulate NF-κB and interferon (IFN) signaling. In the present study, we investigated IKK-ε activation following T cell receptor (TCR)/CD28 stimulation of primary CD4(+) T cells and its role in the stimulation of a type I IFN response. IKK-ε was activated following TCR/CD28 stimulation of primary CD4(+) T cells; however, in T cells treated with poly(I·C), TCR/CD28 costimulation blocked induction of IFN-β transcription.

Therapeutics for HIV-1 reactivation from latency.

Intensive combined antiretroviral therapy successfully suppresses HIV-1 replication and AIDS disease progression making infection manageable, but it is unable to eradicate the virus that persists in long-lived, drug-insensitive and immune system-insensitive reservoirs thus asking for life-long treatments with problems of compliance, resistance, toxicity and cost. These limitations and recent insights into latency mechanisms have fueled a renewed effort in finding a cure for HIV-1 infection. Proposed eradication strategies involve reactivation of the latent reservoir upon induction of viral transcription followed by the elimination of reactivated virus-producing cells by viral cytopathic effect or host immune response.

IRF-8 controls melanoma progression by regulating the cross talk between cancer and immune cells within the tumor microenvironment.

The transcription factor interferon regulatory factor-8 (IRF-8) is crucial for myeloid cell development and immune response and also acts as a tumor suppressor gene. Here, we analyzed the role of IRF-8 in the cross talk between melanoma cells and tumor-infiltrating leukocytes. B16-F10 melanoma cells transplanted into IRF-8-deficient (IRF-8(-/-)) mice grow more rapidly, leading to higher numbers of lung metastasis, with respect to control animals.

The development of immune-modulating compounds to disrupt HIV latency.

Antiretroviral therapy (ART) has proved highly effective in suppressing HIV-1 replication and disease progression. Nevertheless, ART has failed to eliminate the virus from infected individuals. The main obstacle to HIV-1 eradication is the persistence of cellular viral reservoirs.

HIV-1, interferon and the interferon regulatory factor system: an interplay between induction, antiviral responses and viral evasion.

Thirty years after the first isolation of the etiological agent of AIDS, the virus HIV-1 is still a major threat worldwide with millions of individuals currently infected. Although current combination therapies allow viral replication to be controlled, HIV-1 is not eradicated and persists in drug- and immune system-insensitive reservoirs and a cure is still lacking. Pathogens such as HIV-1 that cause chronic infections are able to adapt to the host in a manner that ensures long term residence and survival, via the evolution of numerous mechanisms that evade various aspects of the innate and adaptive immune response.

Adherence to international and national recommendations for the prevention of surgical site infections in Italy: results from an observational prospective study in elective surgery.

Background: An observational prospective study of the perioperative procedures for prevention of surgical site infections (SSIs) was carried out in a tertiary referral teaching hospital in Liguria, Italy, to evaluate their adherence to international and national standards.

Methods: A 1-month survey was performed in all surgical departments, monitored by turns by trained survey teams. Data regarding presurgical patient preparation and intraoperative infection control practices were collected.

An integrated approach identifies IFN-regulated microRNAs and targeted mRNAs modulated by different HCV replicon clones.

Background: Infections with hepatitis C virus (HCV) progress to chronic phase in 80% of patients. To date, the effect produced by HCV on the expression of microRNAs (miRs) involved in the interferon-β (IFN-β) antiviral pathway has not been explored in details. Thus, we compared the expression profile of 24 selected miRs in IFN-β-treated Huh-7 cells and in three different clones of Huh-7 cells carrying a self-replicating HCV RNA which express all viral proteins (HCV replicon system).

Human papillomavirus type 16 E5 protein induces expression of beta interferon through interferon regulatory factor 1 in human keratinocytes.

Crucial steps in high-risk human papillomavirus (HR-HPV)-related carcinogenesis are the integration of HR-HPV into the host genome and loss of viral episomes. The mechanisms that promote cervical neoplastic progression are, however, not clearly understood. During HR-HPV infection, the HPV E5 protein is expressed in precancerous stages but not after viral integration.

The dominant negative β isoform of the glucocorticoid receptor is uniquely expressed in erythroid cells expanded from polycythemia vera patients.

Glucocorticoid receptor (GR) agonists increase erythropoiesis in vivo and in vitro. To clarify the effect of the dominant negative GRβ isoform (unable to bind STAT-5) on erythropoiesis, erythroblast (EB) expansion cultures of mononuclear cells from 18 healthy (nondiseased) donors (NDs) and 16 patients with polycythemia vera (PV) were studied. GRβ was expressed in all PV EBs but only in EBs from 1 ND.

Critical role of IRF-8 in negative regulation of TLR3 expression by Src homology 2 domain-containing protein tyrosine phosphatase-2 activity in human myeloid dendritic cells.

Despite extensive studies that unraveled ligands and signal transduction pathways triggered by TLRs, little is known about the regulation of TLR gene expression. TLR3 plays a crucial role in the recognition of viral pathogens and induction of immune responses by myeloid DCs. IFN regulatory factor (IRF)-8, a member of the IRF family, is a transcriptional regulator that plays essential roles in the development and function of myeloid lineage, affecting different subsets of myeloid DCs.

Expression of IFNγR2 mutated in a dileucine internalization motif reinstates IFNγ signaling and apoptosis in human T lymphocytes.

In T lymphocytes, the internalization of the R2 chain of the IFN-γ receptor (IFN-γR2) prevents the switching-on of pro-apoptotic and anti-proliferative genes induced by the IFN-γ/STAT1 pathway. In fibroblasts, a critical role of controlling the IFN-γR2 internalization is played by the LI(255-256) intracellular motif. Here we show that, in human malignant T cells, the expression of a mutated IFN-γR2 chain in which the LI(255-256) internalization motif is replaced by two alanines (LI(255-256)AA) induces cell surface accumulation of the receptor and reinstates the cell sensitivity to IFN-γ.

Interferon regulatory factor-1 acts as a powerful adjuvant in tat DNA based vaccination.

Genetic vaccines are safe cost-effective approaches to immunization but DNA immunization is an inefficient process. There is, therefore, a pressing need for adjuvants capable of enhancing the immunogenicity and effectiveness of these vaccines. This is particularly important for diseases for which successful vaccines are still lacking, such as cancer and infectious diseases including HIV-1/AIDS.

Interferon regulatory factors in hematopoietic cell differentiation and immune regulation.

Members of the interferon regulatory factor (IRF) family are transcription factors implicated in the regulation of a variety of biological processes. Originally identified as intracellular mediators of the induction and biological activities of interferons, their central role in host resistance to pathogens has recently been confirmed by the recognition of their involvement in the regulation of gene expression in responses triggered by Toll-like receptors and other pattern recognition receptors (PRRs). Their function in regulating the development as well as the activity of hematopoietic cells puts them at the interface between innate and adaptive immune responses.

Generation of a human immunodeficiency virus type 1 chronically infected monkey B cell line expressing low levels of endogenous TRIM5alpha.

Several innate cellular antiviral factors exist in mammalian cells that prevent the replication of retroviruses. Among them, the tripartite motif protein (TRIM)5alpha has been shown to block human immunodeficiency virus type 1 (HIV-1) infection in several types of Old World monkey cells. Here we report a novel HIV-1 chronically infected monkey B cell line, F6/HIV-1, characterized by very low levels of TRIM5alpha expression that allows HIV-1 to overcome the restriction.