Fernando Arenzana-Seisdedos

Bio: Fernando Arenzana-Seisdedos is an academic researcher from Pasteur Institute. The author has contributed to research in topics: Chemokine & Chemokine receptor. The author has an hindex of 70, co-authored 140 publications receiving 22954 citations. Previous affiliations of Fernando Arenzana-Seisdedos include Icahn School of Medicine at Mount Sinai & Centre national de la recherche scientifique.

The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1

Abstract: APUTATIVE chemokine receptor that we previously cloned and termed LESTR1 has recently been shown to function as a co-receptor (termed fusin) for lymphocyte-tropic HIV-1 strains2. Cells expressing CD4 became permissive to infection with T-cell-line-adapted HIV-1 strains of the syncytium-inducing phenotype after transfection with LESTR/fusin complementary DNA. We report here the identification of a human chemokine of the CXC type, stromal cell-derived factor 1 (SDF-1), as the natural ligand for LESTR/fusin, and we propose the term CXCR-4 for this receptor, in keeping with the new chemokine-receptor nomenclature. SDF-1 activates Chinese hamster ovary (CHO) cells transfected with CXCR-4 cDNA as well as blood leukocytes and lymphocytes. In cell lines expressing CXCR-4 and CD4, and in blood lymphocytes, SDF-1 is a powerful inhibitor of infection by lymphocyte-tropic HIV-1 strains, whereas the CC chemokines RANTES, MIP-lα and MIP-1β, which were shown previously to prevent infection with primary, monocyte-tropic viruses3, are inactive. In combination with CC chemokines, which block the infection with monocyte/macrophage-tropic viruses, SDF-1 could help to decrease virus load and prevent the emergence of the syncytium-inducing viruses which are characteristic of the late stages of AIDS4.

G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4

Abstract: Granulocyte colony-stimulating factor (G-CSF) induced hematopoietic stem cell mobilization is widely used for clinical transplantation; however, the mechanism is poorly understood. We report here that G-CSF induced a reduction of the chemokine stromal cell derived factor 1 (SDF-1) and an increase in its receptor CXCR4 in the bone marrow (BM), whereas their protein expression in the blood was less affected. The gradual decrease of BM SDF-1, due mostly to its degradation by neutrophil elastase, correlated with stem cell mobilization. Elastase inhibition reduced both activities. Human and murine stem cell mobilization was inhibited by neutralizing CXCR4 or SDF-1 antibodies, demonstrating SDF-1 CXCR4 signaling in cell egress. We suggest that manipulation of SDF-1 CXCR4 interactions may be a means with which to control the navigation of progenitors between the BM and blood to improve the outcome of clinical stem cell transplantation.

Solution structure and basis for functional activity of stromal cell-derived factor-1; dissociation of CXCR4 activation from binding and inhibition of HIV-1.

Abstract: The three‐dimensional structure of stromal cell‐derived factor‐1 (SDF‐1) was determined by NMR spectroscopy. SDF‐1 is a monomer with a disordered N‐terminal region (residues 1–8), and differs from other chemokines in the packing of the hydrophobic core and surface charge distribution. Results with analogs showed that the N‐terminal eight residues formed an important receptor binding site; however, only Lys‐1 and Pro‐2 were directly involved in receptor activation. Modification to Lys‐1 and/or Pro‐2 resulted in loss of activity, but generated potent SDF‐1 antagonists. Residues 12–17 of the loop region, which we term the RFFESH motif, unlike the N‐terminal region, were well defined in the SDF‐1 structure. The RFFESH formed a receptor binding site, which we propose to be an important initial docking site of SDF‐1 with its receptor. The ability of the SDF‐1 analogs to block HIV‐1 entry via CXCR4, which is a HIV‐1 coreceptor for the virus in addition to being the receptor for SDF‐1, correlated with their affinity for CXCR4. Activation of the receptor is not required for HIV‐1 inhibition.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

THE NF-κB AND IκB PROTEINS: New Discoveries and Insights

Abstract: ▪ Abstract The transcription factor NF-κB has attracted widespread attention among researchers in many fields based on the following: its unusual and rapid regulation, the wide range of genes that it controls, its central role in immunological processes, the complexity of its subunits, and its apparent involvement in several diseases. A primary level of control for NF-κB is through interactions with an inhibitor protein called IκB. Recent evidence confirms the existence of multiple forms of IκB that appear to regulate NF-κB by distinct mechanisms. NF-κB can be activated by exposure of cells to LPS or inflammatory cytokines such as TNF or IL-1, viral infection or expression of certain viral gene products, UV irradiation, B or T cell activation, and by other physiological and nonphysiological stimuli. Activation of NF-κB to move into the nucleus is controlled by the targeted phosphorylation and subsequent degradation of IκB. Exciting new research has elaborated several important and unexpected findings that...

Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.

Abstract: NF-κB (nuclear factor-κB) is a collective name for inducible dimeric transcription factors composed of members of the Rel family of DNA-binding proteins that recognize a common sequence motif. NF-κ...

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.