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The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus initially appeared in Wuhan, Hubei Province, China has caused a novel coronavirus disease (COVID-19) [1] . The disease is rapidly spread around the world causing thousands of deaths and posing critical challenges for public health and clinical research in the world. The outbreak was declared by the World Health Organization (WHO) as a public health emergency of international concern. Nowadays, there are more than 18 millions of confirmed cases of coronavirus across the world with a total of 702,903 deaths [2] . In Morocco, there are 28,500 confirmed cases and 345 deaths. Forecasts for the cumulative number of confirmed, recovered, active and death cases were recently provided [3] . To manage the pandemic spread several countries adopted proactive and preventive measures including home confinement of the population. However, there is evidence that these measures, particularly home confinement, can cause unprecedented disruption in the well-being of the population. Being forced to stay at home and the daily activities’ restrictions could impact the citizens’ health-related quality of life (HRQoL) and behavior-related lifestyle. It has been reported that the COVID-19 pandemic has an impact on psychological behaviors [4] , mental health [5] and anxiety/depression [6] . The Moroccan population was under home confinement from March 20, 2020. Assessing rapidly and simply the HRQoL during crisis such as the home confinement is a challenge of interest to provide speedy information to authorities which allow best management of damages yielding in crisis situation. The EQ-5D instrument is a generic questionnaire developed by the Euroqol group for measuring the HRQoL by combining five health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) [7] . The EQ-5D instrument is translated into more than 300 languages and exhibit good reliability and validity in both patients and general population. Herein, we used the EQ-5D-5L instrument to assess for the first time the impact of the home confinement on the HRQoL. Also, we evaluated the changes in behaviors by asking some questions related to lifestyle before and during the home confinement. These data can help the Moroccan authorities and other countries to more understand the impact of this crisis on citizens and therefore to set up adequate protocols for managing the post-confinement or possible future crisis. We provided two datasets: (1) data we collected before confinement from a sample of 484 individuals describing their HRQoL [8] and (2) data we collected during the home confinement period from a sample of 537 individuals describing their HRQoL and behavior-related lifestyle.

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Epstein-Barr virus (EBV) induces IntroductionEpstein-Barr virus (EBV) was first reported to be associated with Burkitt lymphoma (BL). EBV is able to immortalize B cells both in vitro and in vivo. EBV is also the etiologic agent of infectious mononucleosis, a benign viral disease of young adults that regresses spontaneously. In most cases, primary EBV infection is asymptomatic. Epidemiologic and serologic studies showed that EBV is widely distributed in humans around the world and that more than 95% of adults have been infected by EBV in their past. The ability to grow EBV-infected B-cell lines from peripheral blood mononuclear cells (PBMCs) of EBV-seroconverted healthy subjects leads to the conclusion that this virus persists as a clinically silent infection for the lifetime of the infected host. 1 Nevertheless, it is of note that the virus remains continuously active in immunocompetent individuals even though at very low levels. 2 The EBV genome consists of a 180-kb double-stranded DNA that remains stable in the cell nucleus in an episomal form. In vitro immortalization of B cells by EBV is due to the expression of a restricted set of viral genes, the so-called latency III program, coding for latent membrane proteins (LMP1, LMP2a, LMP2b), Epstein-Barr nuclear antigens (EBNA1, 2, 3A, 3B, 3C, LP), and small noncoding RNAs (EBERs), and leads to the establishment of lymphoblastoid cell lines (LCLs). 3 Among these genes, EBNA1 is responsible for episomal maintenance of the EBV genome. 4 EBNA2 alone is responsible for the expression of the entire set of genes of the latency III program. 5 EBNA2 reroutes the Notch pathway by targeting RBP-jkappa. 6 EBNA2 is also the main viral transactivator of the BNLF1 gene coding for LMP1. LMP1 mimics a constitutively activated receptor of the TNF receptor family through aggregation of TRAF/TRADD molecules. 7,8 In vivo, the latency III program is expressed in newly infected B-blasts during primary EBV infection. 9 Most of these newly EBV-infected B-blasts are killed by cytotoxic T cells. However, some EBVinfected B-blasts are considered to follow the normal process of B-cell maturation until the B-cell memory stage. 10 The B-cell memory compartment constitutes the EBV reservoir in humans. EBV is almost silent in its reservoir. [10][11][12] The immune response against EBV is associated with a dramatic oligoclonal increase in EBV-specific CD8 cytotoxic T cells during the initial phase of primary EBV infection. [13][14][15] Cytotoxic T cells may prevent in vitro de novo infection of B cells. 16,17 In Purtilo syndrome, the defect of SH2D1A/SAP gene alters T-cell signaling in response to antigen. 18 The SAP signaling For personal use only. on May 10, 2018. by guest www.bloodjournal.org From pathway plays a key role in the cytolytic activity of T cells against EBV-positive targets, 19 and Purtilo syndrome is characterized by fatal infectious mononucleosis after primo-infection. 18 Emergence of EBV-associated lymphoma in patients with acquired T-cell immunodeficiencies such as HIV infecti...

Chemotherapeutic drugs such as fludarabine*, doxorubicin or cisplatin are very potent activators of the anti-oncogene p53. Convergent studies suggest that p53 and STAT1 (signal transducer and activator of transcription 1) cooperate in the induction of cell death. We show that these drugs are also activators of STAT1 in p53-expressing cells, but not in p53-null cells. STAT1 activation was obtained in the presence of both the secretion inhibitor brefeldine A and the inhibitor of RNA synthesis, actinomycin D. p53-dependent STAT1 activation was reversed by overexpression of MDM2 and siRNAs against p53. Genetic analysis of p53 showed that expression of transcriptionally inactive p53 punctual mutants markedly increased Y701-STAT1 phosphorylation, and suggests that the p53 DNA-binding domain was alternatively involved in STAT1 activation or p53 multimerization. Immunoprecipitation experiments showed that ataxia telangiectasia mutated, p53, STAT1 and c-Abl1 (Abelson murine leukaemia viral oncogene homologue 1) were associated together. Treatment of cells with the c-Abl1 tyrosine kinase inhibitor STI571 decreased STAT1 activation by genotoxic drugs. Finally, genotoxic agents sensitized cells in response to very low doses of both interferon a and c (IFNa and c). These results show that genotoxic drugs induce STAT1 activation, an effect that depends on p53 protein but not on p53 transcriptional activity, and point to a novel pathway of STAT1 activation by genotoxic drugs, with involvement of c-Abl1 tyrosine kinase in sensitizing cells to IFN response.

Constitutive activation of signal transducer and activator of transcription 1 (STAT1) is a distinctive feature of Epstein-Barr virus (EBV)-immortalized B cells (lymphoblastoid cell lines [LCLs]). The expression of STAT1The Epstein-Barr virus (EBV) is the causal agent of infectious mononucleosis and is associated with severe infections in immunocompromised patients. In addition, EBV is associated with malignancies such as Burkitt lymphoma, nasopharyngeal carcinoma, and Hodgkin's lymphoma (30).In primary lymphocyte infection, cell proliferation is stimulated by a set of viral gene products termed the latency III program, which is also characteristic of EBV-transformed lymphoblastoid cell lines (LCLs) (31). Among the latency III viral gene products, the latent membrane protein 1 (LMP1) is essential for the EBV-induced transformation of primary B lymphocytes (22). The oncogenic properties of LMP1 are associated with stimulation of DNA synthesis (28), stimulation of the transcription of antiapoptotic genes (9, 34), and suppression of cellular senescence (37). LMP1 is a transmembrane protein, analogous to a constitutively activated CD40 receptor, although structurally different (18). Specialized regions (CTAR1 and CTAR2) of the cytoplasmic domain of LMP1 recruit components of the TNF-R signaling pathway and activate the transcriptional factor NF-B. The two regions are not equivalent: CTAR1 operates by recruiting TRAF1, -2, and -3, and CTAR2 operates by recruiting RIP and TRADD (4,14,21).Constitutive STAT1 activation has been observed in EBVassociated tumors, including nasopharyngeal carcinoma (9), and in LCLs (10, 35). The STATs are transcription factors that are activated after triggering of cells with cytokines. Although most STATs, including STAT3, STAT4, and STAT5, are involved in the proliferative response of cells to cytokines, STAT1 and STAT2 are associated with the cellular response to interferons (IFNs), which reduce cell proliferation and increase apoptosis. Thus, in the context of EBV-transformed LCLs, the activation of STAT1 raises the question of its function. We previously observed that inhibition of STAT1 in LCLs by overexpression of an inhibitory form of STAT1 (STAT1␤) reduces drug-induced apoptosis and increases the growth rate of cells (3), demonstrating that even in the context of EBVtransformed cells, STAT1 remains an inhibitor of cell proliferation. Nevertheless, expression of LMP1 itself was shown to be sufficient to induce a higher level of STAT1 expression (29), but the mechanism involved remains unclear. A direct activation of STATs was suggested, after interaction of JAK3 with a

The Epstein-Barr virus (EBV) oncoprotein latent membrane protein 1 (LMP1) is thought to act as the major transforming protein in various cell types, by rerouting the tumor necrosis factor receptor family signaling pathway. Despite this implication in EBV-associated transformation of cells, LMP1 toxicity is a well-known but poorly studied feature, perhaps because it contradicts its role in transformation. We show that LMP1 physiological levels are very heterogeneous and that the highest levels of LMP1 correlate with