We identified a stem cell donor with chromosomally integrated human herpesvirus (HHV)–6 and monitored the recipient for HHV-6 after transplantation. The appearance and subsequent increase in HHV-6 ...load paralleled engraftment and an increase in white blood cell count. Fluorescent in situ hybridization analysis showed integrated HHV-6 on chromosome band 17p13.3 in the donor and in the recipient after transplantation but not in the recipient before transplantation. The increase in viral load due to the genetic transmission of integrated HHV-6 could have been misinterpreted as substantial active infection and, thus, led to the administration of toxic antiviral therapy. We suggest that the confounding influence of integration be considered in laboratory investigations associating HHV-6 with disease
1 Department of Infection, Division of Infection and Immunity, Royal Free and University College Medical School of UCL, London, UK
2 Virus Genomics Team, Wellcome Trust Sanger Institute, Cambridge, ...UK
Correspondence Duncan A. Clark duncan.clark{at}bartsandthelondon.nhs.uk
The lytic gene expression of several members of the human herpesvirus family has been profiled by using gene-expression microarrays; however, the lytic cascade of roseoloviruses has not been studied in similar depth. Based on the complete DNA genome sequences of human herpesvirus 6 variant A (HHV-6A) and variant B (HHV-6B), we constructed a cDNA microarray containing DNA probes to their predicted open reading frames, plus 914 human genes. Gene-expression profiling of HHV-6B strain Z29 in SupT1 cells over a 60 h time-course post-infection, together with kinetic classification of the HHV-6B genes in the presence of either cycloheximide or phosphonoacetic acid, allowed the placement of HHV-6B genes into defined kinetic classes. Eighty-nine HHV-6B genes were divided into four different expression kinetic classes: eight immediate-early, 44 early, 33 late and four biphasic. Clustering of genes with similar expression profiles implied a shared function, thus revealing possible roles of previously uncharacterized HHV-6B genes.
The ArrayExpress accession numbers for the microarray data generated in this paper are E-MEXP-2129 and E-MEXP-2130.
Supplementary methods, figures, tables and references are available with the online version of this paper.
Reply to Boutolleau et al. and Luppi et al Clark, Duncan A.; Tsao, Edward H. F.; Leong, Hoe Nam ...
The Journal of infectious diseases,
10/2006, Letnik:
194, Številka:
7
Journal Article
On March 28– 29, 2017, the National Cancer Institute (NCI) Thoracic Malignacy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation ...convened the NCI–International Association for the Study of Lung Cancer– Mesothelioma Applied Research Foundation Mesothelioma Clinical Trials Planning Meeting in Bethesda, Maryland. The goal of the meeting was to bring together lead academicians, clinicians, scientists, and the U.S. Food and Drug Administration to focus on the development of clinical trials for patients in whom malignant pleural mesothelioma has been diagnosed. In light of the discovery of new cancer targets affecting the clinical development of novel agents and immunotherapies in malignant mesothelioma, the objective of this meeting was to assemble a consensus on at least two or three practice-changing multimodality clinical trials to be conducted through NCI’s National Clinical Trials Network.
As many biosimilars come to market in the next several years, their use in oncology will play an important role in the future care of patients with cancer. ASCO is committed to providing education ...and guidance to the oncology community on the use of biosimilars in the cancer setting; therefore, ASCO has developed this statement to offer guidance in the following areas: (1) naming, labeling, and other regulatory considerations, (2) safety and efficacy of biosimilars, (3) interchangeability, switching, and substitution, (4) value of biosimilars, and (5) prescriber and patient education.
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a strong genetic component characterized by autoantibody production and a type I interferon signature. Here we report a ...missense variant (g.74779296G>A; p.Arg90His) in NCF1, encoding the p47
subunit of the phagocyte NADPH oxidase (NOX2), as the putative underlying causal variant that drives a strong SLE-associated signal detected by the Immunochip in the GTF2IRD1-GTF2I region at 7q11.23 with a complex genomic structure. We show that the p.Arg90His substitution, which is reported to cause reduced reactive oxygen species (ROS) production, predisposes to SLE (odds ratio (OR) = 3.47 in Asians (P
= 3.1 × 10
), OR = 2.61 in European Americans, OR = 2.02 in African Americans) and other autoimmune diseases, including primary Sjögren's syndrome (OR = 2.45 in Chinese, OR = 2.35 in European Americans) and rheumatoid arthritis (OR = 1.65 in Koreans). Additionally, decreased and increased copy numbers of NCF1 predispose to and protect against SLE, respectively. Our data highlight the pathogenic role of reduced NOX2-derived ROS levels in autoimmune diseases.
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