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In this review, the interaction between conventional T cells and T cells for haematopoietic reconstitution, and the role of T cells for the control of CMV/EBV reactivation as well as for the control of tumour relapse are discussed. In SARS-CoV-2 infections [[2]], single-cell transcriptome analysis was used to correlate markers of activation, differentiation and tissue residence with the T cell receptor characteristics of T cell subsets. T cells are members of "unconventional" T cells that combine the properties of adaptive T lymphocytes and innate cells such as NK cells. [Extracted from the article]

Natural killer (NK) cells mount an immune response against hepatitis C virus (HCV) infection and can be activated by several cytokines, including interleukin-2 (IL-2), IL-15, and interferon-alpha (IFN-α). By exploiting the Huh7.5 hepatoma cell line infected with the HCV JFH1 genome, we provide novel insights into the antiviral effector functions of human primary NK cells after cytokine stimulation. NK cells activated with IFN-α (IFNα-NKs) had enhanced contact-dependent and -independent responses as compared with NK cells activated with IL-2/IL-15 (IL2/IL15-NKs) and could inhibit HCV replication both in vitro and in vivo. Importantly, IFN-α, but not IL-2/IL-15, protected NK cells from the functional inhibition exerted by HCV. By performing flow cytometry, multiplex cytokine profiling, and mass-spectrometry-based proteomics, we discovered that IFNα-NKs secreted high levels of galectin-9 and interferon-gamma (IFN-γ), and by conducting neutralization assays, we confirmed the major role of these molecules in HCV suppression. We speculated that galectin-9 might act extracellularly to inhibit HCV binding to host cells and downstream infection. In silico approaches predicted the binding of HCV envelope protein E2 to galectin-9 carbohydrate-recognition domains, and co-immunoprecipitation assays confirmed physical interaction. IFN-γ, on the other hand, triggered the intracellular expressions of two antiviral gate-keepers in target cells, namely, myxovirus-1 (MX1) and interferon-induced protein with tetratricopeptide repeats 1 (IFIT1). Collectively, our data add more complexity to the antiviral innate response mediated by NK cells and highlight galectin-9 as a key molecule that might be exploited to neutralize productive viral infection. [ABSTRACT FROM AUTHOR]

Immune homeostasis is achieved by balancing the activating and inhibitory signal transduction pathways mediated via cell surface receptors. Activation allows the host to mount an immune response to endogenous and exogenous antigens; suppressive modulation via inhibitory signaling protects the host from excessive inflammatory damage. The checkpoint regulation of myeloid cells during immune homeostasis raised their profile as important cellular targets for treating allergy, cancer and infectious disease. This review focuses on the structure and signaling of inhibitory receptors on myeloid cells, with particular attention placed on how the interplay between viruses and these receptors regulates antiviral immunity. The status of targeting inhibitory receptors on myeloid cells as a new therapeutic approach for antiviral treatment will be analyzed. [ABSTRACT FROM AUTHOR]

HLA-B*57:01 is an HLA allelic variant associated with positive outcomes during viral infections through interactions with T cells and NK cells, but severe disease in persons treated with the anti-HIV-1 drug abacavir. The role of HLA-B*57:01 in the context of HSV infection is unknown. We identified an HLA-B*57:01-restricted CD8 T-cell epitope in the ICP22 (US1) protein of HSV-2. CD8 T cells reactive to the HSV-2 ICP22 epitope recognized the orthologous HSV-1 peptide, but not closely related peptides in human IFNL2 or IFNL3. Abacavir did not alter the CD8 T-cell recognition of the HSV or self-derived peptides. Unexpectedly, a tetramer of HSV-2 ICP22 epitope (228–236) and HLA-B*57:01 bound both CD8 T cells and NK cells. Tetramer specificity for KIR3DL1 was confirmed using KIR3DL1 overexpression on non-human primate cells lacking human KIR and studies with blocking anti-KIR3DL1 antibody. Interaction with KIR3DL1 was generalizable to donors lacking the HLA-B*57:01 genotype or HSV seropositivity. These findings suggest a mechanism for the recognition of HSV infection by NK cells or KIR-expressing T cells via KIR3DL1. [ABSTRACT FROM AUTHOR]

Human Herpesvirus 6 (HHV-6) is a set of two closely related herpes viruses known as HHV-6A and HHV-6B. Both are lymphotropic viruses that establish latency in the host. The ability to evade the immune responses of effector cells is likely a major factor contributing to the development of a persistent HHV-6A/B (collectively termed HHV-6) infection. Natural killer (NK) cells are lymphocytes that, along with neutrophils and monocytes/macrophages, participate in the critical innate immune response during viral infections, but can also mediate the antigen-specific memory responses generally associated with adaptive immunity. NK cells compose the first barrier that viruses must break through to continue replication and dissemination, and a weak NK cell response may predispose an individual to chronic viral infections. Both HHV-6A and HHV-6B can interfere with NK cell-mediated anti-viral responses but the mechanisms by which each of these viruses affect NK cell activity differs. In this review, we will explore the nuanced relationships between the two viruses and NK cells, discussing, in addition, relevant disease associations. [ABSTRACT FROM AUTHOR]

In contrast to activated CD4+ T cells and differentiated macrophages, resting CD4+ T cells and monocytes are non-permissive for HIV-1 replication. The mediators which regulate the resting or quiescent phenotype are often actively involved in the restriction of viral replication and the establishment and maintenance of viral latency. Recently, certain microRNAs which are highly expressed in resting cells have been implicated in this capacity, inhibiting the expression of cellular proteins that are also viral co-factors; following activation these microRNAs exhibit decreased expression, while their targets are correspondingly up-regulated, contributing to a favorable milieu for virus replication. Other microRNAs exhibiting a similar expression pattern in resting and activated cells have been shown to directly target the HIV-1 genome. In this review we will discuss the resting state and the causes behind viral restriction in resting cells, with emphasis on the role of microRNAs. [ABSTRACT FROM AUTHOR]

SARS-CoV-2, a member of the coronavirus family, is the causative agent of the COVID-19 pandemic. Currently, there is still an urgent need in developing an efficient therapeutic intervention. In this study, we aimed at evaluating the therapeutic effect of a single intranasal treatment of the TLR3/MDA5 synthetic agonist Poly(I:C) against a lethal dose of SARS-CoV-2 in K18-hACE2 transgenic mice. We demonstrate here that early Poly(I:C) treatment acts synergistically with SARS-CoV-2 to induce an intense, immediate and transient upregulation of innate immunity-related genes in lungs. This effect is accompanied by viral load reduction, lung and brain cytokine storms prevention and increased levels of macrophages and NK cells, resulting in 83% mice survival, concomitantly with long-term immunization. Thus, priming the lung innate immunity by Poly(I:C) or alike may provide an immediate, efficient and safe protective measure against SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Roughly 30 years ago, in 1989-90, I had the privilege of being an EMBO fellow and a post doc in Peter's lab in Cambridge, England. We were all very sorry to hear that our highly esteemed colleague and one of the true pioneers of complement research, Professor, Sir Peter J. Lachmann passed away on St. Stephen's Day, 26 December 2020 at the age of 89 years. Everybody remembers Peter's and his wife's, Sylvia's, hospitality, when they invited students and colleagues to their home. [Extracted from the article]

An impediment to curing HIV-1 infection is the persistence of latently infected cells in ART-treated people living with HIV (PLWH). A key strategy for curing HIV-1 infection is to activate transcription and translation of latent virus using latency reversing agents (LRAs) and eliminate cells harboring reactivated virus via viral cytopathic effect or immune clearance. In this review, we provide an overview of available LRAs and their use in clinical trials. Furthermore, we describe recent data suggesting that CD8+ T cells promote HIV-1 latency in the context of ART, even in the presence of LRAs, which might at least partially explain the clinical inefficiency of previous "shock and kill" trials. Here, we propose a novel cure strategy called "unlock, shock, disarm, and kill". The general premise of this strategy is to shut down the pro-latency function(s) of CD8+ T cells, use LRAs to reverse HIV-1 latency, counteract anti-apoptotic molecules, and engage natural killer (NK) cells to mediate the killing of cells harboring reactivated latent HIV-1. [ABSTRACT FROM AUTHOR]

The role of the adaptive microenvironment components in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection is widely researched, but remains unclear. Studying the common dynamics of adaptive immune response changes can help understand the pathogenesis of coronavirus disease 2019 (COVID-19), especially in critical patients. The aim of the present study was to determine the cytokines concentration and leukocyte subpopulations profiles in the severe COVID-19 (n = 23) and critical (n = 18) COVID-19 group distinguished by the computed tomography (CT) severity score. We observed lower percentage of lymphocyte subpopulation, higher neutrophils to lymphocytes ratio (NLR) and higher IL-6 concentration in critical COVID-19 group than in severe group. CT severity score was negative correlated with proportion of lymphocytes, lymphocytes T, CD4+ cells, Treg cells and NK cells and positive correlated with neutrophils, NLR, and IL-6. In critical group more correlations between cytokines and lymphocytes were observed, mainly between TNF-α, IL-1β and lymphocyte subpopulations. The collective assessment of the cytokine profile, leukocyte subpopulations and the CT severity score can help to characterize and differentiate patient in advanced COVID-19 than the study of single parameters. We have shown that the interconnection of elements of the adaptive microenvironment can play an important role in critical COVID-19 cases. [ABSTRACT FROM AUTHOR]