Deletion of the non-adjacent genes UL148 and UL148D impairs human cytomegalovirus-mediated TNF receptor 2 surface upregulation.

Human cytomegalovirus (HCMV) is a prototypical ß-herpesvirus which frequently causes morbidity and mortality in individuals with immature, suppressed, or senescent immunity. HCMV is sensed by various pattern recognition receptors, leading to the secretion of pro-inflammatory cytokines including tumor necrosis factor alpha (TNFα). TNFα binds to two distinct trimeric receptors: TNF receptor (TNFR) 1 and TNFR2, which differ in regard to their expression profiles, affinities for soluble and membrane-bound TNFα, and down-stream signaling pathways. While both TNF receptors engage NFκB signaling, only the nearly ubiquitously expressed TNFR1 exhibits a death domain that mediates TRADD/FADD-dependent caspase activation. Under steady-state conditions, TNFR2 expression is mainly restricted to immune cells where it predominantly submits pro-survival, proliferation-stimulating, and immune-regulatory signals. Based on the observation that HCMV-infected cells show enhanced binding of TNFα, we explored the interplay between HCMV and TNFR2. As expected, uninfected fibroblasts did not show detectable levels of TNFR2 on the surface. Intriguingly, however, HCMV infection increased TNFR2 surface levels of fibroblasts. Using HCMV variants and BACmid-derived clones either harboring or lacking the ULb' region, an association between TNFR2 upregulation and the presence of the ULb' genome region became evident. Applying a comprehensive set of ULb' gene block and single gene deletion mutants, we observed that HCMV mutants in which the non-adjacent genes UL148 or UL148D had been deleted show an impaired ability to upregulate TNFR2, coinciding with an inverse regulation of TACE/ADAM17.

Staggered enforcement of infection control and prevention measures following four consecutive potential laboratory exposures to imported Brucella melitensis.

From 2015 until 2020, Brucella melitensis was isolated four times in our microbiology laboratory. All patients had travelled in endemic-areas. Immediately after the first occurrence, all laboratory staff were risk-stratified and preventive and protective measures were applied according to CDC guidelines. Nineteen workers were exposed and needed chemoprophylaxis and follow-up. At each subsequent occurrence, risk analysis was performed, and additional measures were implemented accordingly, leading to a progressive reduction of exposed staff members to none the fourth time. We describe here the additional measures that permitted this important exposure reduction.

The Human Cytomegalovirus pUL145 Isoforms Act as Viral DDB1-Cullin-Associated Factors to Instruct Host Protein Degradation to Impede Innate Immunity.

Human cytomegalovirus (HCMV) causes diseases in individuals with immature or compromised immunity. To evade immune control, HCMV evolved numerous antagonists targeting the interferon system at multiple levels. By comparative analysis of naturally arising variants of the most widely studied HCMV strain, AD169, and a panel of targeted mutants, we uncover the UL145 gene as indispensable for STAT2 downregulation. Ribosome profiling confirms the translation of the canonical pUL145 protein (pUL145-Long) and newly identifies a shorter isoform (pUL145-Short). Both isoforms recruit DDB1-containing ubiquitin ligases to induce proteasomal degradation of STAT2. An alanine-scanning mutagenesis discloses the DDB1 interaction motif of pUL145 that resembles the DDB1-binding interface of cellular substrate receptors of DDB1-containing ubiquitin ligases. Thus, pUL145 constitutes a viral DDB1-cullin-associated factor (vDCAF), which mimics cellular DCAFs to exploit the ubiquitin-proteasome system to impede antiviral immunity. Notably, the viral exploitation of the cullins can be targeted to restore the efficacy of the host immune response.

Paul Bastenie et la recherche en diabétologie à l'ULB.

The present chapter deals with the contribution of Professor Paul A. Bastenie, as Chief of the Department of Medicine of the Saint-Pierre Hospital and Director of the Laboratory of Experimental Medicine at Brussels Free University, in the field of diabetes with emphasis on the role of insulin in glucose homeostasis. The knowledge and experimental work under consideration is covering the period from 1955 to 1974. They entail not only three treatises contributed by Bastenie but also fundamental and clinical investigations, such as those presented in eight doctoral dissertations submitted for aggregation examination at Brussels Free University. These theses are dealing with the measurement of glucose assimilation (V. Conard), the measurement of insulin activity in men (J.R.M. Franckson), the mechanisms of action of hypoglycemic drugs (R. Bellens), the study of energy metabolism in children (H. Loeb), the study of insulin secretion in vitro (W. Malaisse), the distribution of insulin in body fluids as influenced by the permeability and structure of blood capillaries (E. Rasio), the regulation of the extra-hepatic metabolism of ketone bodies in anesthetized dogs (E.O. Balasse) and the use of radioiodinated insulin as tracers in biology (H.A. Ooms).

Le présent article concerne la contribution du Professeur Paul A. Bastenie, en tant que Chef du Département de Médecine à l'Hôpital Saint-Pierre et de Directeur du Laboratoire de Médecine expérimentale à l'Université libre de Bruxelles, dans le domaine de la diabétologie, en particulier le rôle de l'insuline dans l'homéostasie glucidique. Le travail expérimental pris en considération couvre la période de 1955 à 1974. Il comporte non seulement trois traités contribués par Bastenie, mais également des investigations fondamentales et cliniques telles que celles présentées à l'Université libre de Bruxelles dans huit thèses d'agrégation de l'enseignement supérieur. Celles-ci concernent la mesure de l'assimilation de glucose (V. Conard), la mesure de l'activité de l'insuline chez l'homme (J.R.M. Franckson), les mécanismes d'action des drogues hypoglycémiantes (R. Bellens), le métabolisme énergétique de l'enfant (H. Loeb), la sécrétion insulinique in vitro (W. Malaisse), le passage capillaire de l'insuline (E. Rasio), le métabolisme extra-hépatique des corps cétoniques in vivo (E.O. Balasse) et l'emploi des insulines radioiodées comme traceurs en biologie (H.A. Ooms).

[Satirical revues produced by the students in medicine of the Université libre de Bruxelles from 1944 to 2014]. / Les revues des étudiants en Médecine de l'Université libre de Bruxelles de 1944 à 2014.

The paper deals with the content of the 10 satirical revues organized by the students in medicine of the Université libre de Bruxelles (ULB) from 1944 to 2014. That analysis allows identifying the events as well the figures which have left their mark in the Faculty of medicine of ULB during this period, at least according to the view of the students.

Le contenu des dix revues satiriques organisées par les étudiants en Médecine de l'Université libre de Bruxelles entre 1944 et 2014 est analysé dans cet article. Cette analyse permet de dégager les évènements et les personnages de la vie de la Faculté qui ont marqué les étudiants au cours de cette période.

Human Cytomegalovirus Latency: Approaching the Gordian Knot.

Herpesviruses have evolved exquisite virus-host interactions that co-opt or evade a number of host pathways to enable the viruses to persist. Persistence of human cytomegalovirus (CMV), the prototypical betaherpesvirus, is particularly complex in the host organism. Depending on host physiology and the cell types infected, CMV persistence comprises latent, chronic, and productive states that may occur concurrently. Viral latency is a central strategy by which herpesviruses ensure their lifelong persistence. Although much remains to be defined about the virus-host interactions important to CMV latency, it is clear that checkpoints composed of viral and cellular factors exist to either maintain a latent state or initiate productive replication in response to host cues. CMV offers a rich platform for defining the virus-host interactions and understanding the host biology important to viral latency. This review describes current understanding of the virus-host interactions that contribute to viral latency and reactivation.

Coding potential of UL/b' from the initial source of rhesus cytomegalovirus Strain 68-1.

Rhesus cytomegalovirus (RhCMV) 68-1 is the prototypic strain of RhCMV that has been used for pathogenesis and vaccine development. We determined the complete sequence of the RhCMV 68-1 UL/b' region directly from the original urine from which RhCMV 68-1 was isolated in 1968, and compared it to other RhCMVs. The laboratory passaged RhCMV 68-1 has inversions, deletions, and stop codons in UL/b' that are absent in the original isolate and other low passage RhCMV isolates. Fourteen of the 17 open reading frames (ORFs) in 68-1 UL/b' in the original isolate share >95% amino acid identity with low passage RhCMV. The original isolate retains 6 ORFs that encode α-chemokine-like proteins, including RhUL146 and RhUL146b that share only 92% and 81% amino acid identity, respectively, with a contemporary low passage RhCMV isolate. Identification of the original RhCMV 68-1 UL/b' sequence is important for using RhCMV 68-1 in pathogenesis and vaccine studies.