Hepatitis B Virus X Protein Inhibits P53 Sequence-Specific DNA Binding
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Calcium and Covid-19 1 Conflicts Over Calcium and the Treatment of Covid
Calcium and Covid-19 1 Conflicts over calcium and the treatment of Covid-19 Bernard Crespi 1 and Joe Alcock 2 1 Department of Biological Sciences, 8888 University Drive, Simon Fraser University, Burnaby V5A1S6, British Columbia, Canada 2 Department of Emergency Medicine, University of New Mexico, Albuquerque, New Mexico 87131, USA Word counts: Abstract 147, Main Text 2966 © The Author(s) 2020. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Calcium and Covid-19 2 Abstract Several recent studies have provided evidence that use of calcium channel blockers, especially amlodipine and nifedipine, can reduce mortality from Covid-19. Moreover, hypocalcemia (a reduced level of serum ionized calcium) has been shown to be strongly positively associated with Covid-19 severity. Both effectiveness of CCBs as antiviral therapy, and positive associations of hypocalcemia with mortality, have been demonstrated for many other viruses as well. We evaluate these findings in the contexts of virus-host evolutionary conflicts over calcium metabolism, and hypocalcemia as either pathology, viral manipulation, or host defence against pathogens. Considerable evidence supports the hypothesis that hypocalcemia represents a host defence. Indeed, hypocalcemia may exert antiviral effects in a similar manner as do CCBs, through interference with calcium metabolism in virus-infected cells. Prospective clinical studies that address the efficacy of CCBs and hypocalcemia should provide novel insights into the pathogenicity and treatment of Covid-19 and other viruses. -
Oncogenes of DNA Tumor Viruses1
[CANCER RESEARCH 48. 493-496. February I. 1988] Perspectives in Cancer Research Oncogenes of DNA Tumor Viruses1 Arnold J. Levine Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544 Experiments carried out over the past 10-12 years have the cellular oncogenes. It will attempt to identify where more created a field or approach which may properly be termed the information is required or contradictions appear in the devel molecular basis of cancer. One of its major accomplishments oping concepts. Finally, this communication will examine ex has been the identification and understanding of some of the amples of cooperation between oncogenes and other gene prod functions of a group of cancer-causing genes, the oncogenes. ucts which modify the mode of action of the former. If we are The major path to the oncogenes came from the study of cancer- on the right track, then general principles may well emerge. causing viruses. The oncogenes have been recognized and stud Tumor formation in animals or transformation in cell culture ied by two separate but related groups of virologists focusing has been demonstrated with many different DNA-containing upon either the DNA (1) or RNA (2) tumor viruses (they even viruses (1). In most cases it has been possible to identify one or have separate meetings now that these fields have grown so a few viral genes and their products that are responsible for large). From their studies it has become clear that the oncogenes transformation or, in some cases, tumorigenesis. A list of these of each virus type have very different origins. -
Tätigkeitsbericht 2007/2008
Tätigkeitsbericht 2007/2008 8 200 / 7 0 20 Tätigkeitsbericht Stiftung bürgerlichen Rechts Martinistraße 52 · 20251 Hamburg Tel.: +49 (0) 40 480 51-0 · Fax: +49 (0) 40 480 51-103 [email protected] · www.hpi-hamburg.de Impressum Verantwortlich Prof. Dr. Thomas Dobner für den Inhalt Dr. Heinrich Hohenberg Redaktion Dr. Angela Homfeld Dr. Nicole Nolting Grafik & Layout AlsterWerk MedienService GmbH Hamburg Druck Hartung Druck + Medien GmbH Hamburg Titelbild Neu gestaltete Fassade des Seuchenlaborgebäudes Tätigkeitsbericht 2007/2008 Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg Martinistraße 52 · 20251 Hamburg Postfach 201652 · 20206 Hamburg Telefon: +49-40/4 80 51-0 Telefax: +49-40/4 80 51-103 E-Mail: [email protected] Internet: www.hpi-hamburg.de Das Heinrich-Pette-Institut ist Mitglied der Leibniz-Gemeinschaft (WGL) Internet: www.wgl.de Inhaltsverzeichnis Allgemeiner Überblick Vorwort ................................................................................................... 1 Die Struktur des Heinrich-Pette-Instituts .............................................. 2 Modernisierung des HPI erfolgreich abgeschlossen ............................ 4 60 Jahre HPI .............................................................................................. 5 Offen für den Dialog .............................................................................. 6 Preisverleihungen und Ehrungen .......................................................... 8 Personelle Veränderungen in -
Hemagglutinin Stalk- and Neuraminidase-Specific
crossmark Hemagglutinin Stalk- and Neuraminidase-Specific Monoclonal Antibodies Protect against Lethal H10N8 Influenza Virus Infection in Mice Teddy John Wohlbold,a,b Veronika Chromikova,a Gene S. Tan,a Philip Meade,a,b Fatima Amanat,a Phillip Comella,a,b Ariana Hirsh,a Florian Krammera Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USAa; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USAb ABSTRACT Downloaded from Between November 2013 and February 2014, China reported three human cases of H10N8 influenza virus infection in the Jiangxi province, two of which were fatal. Using hybridoma technology, we isolated a panel of H10- and N8-directed monoclonal anti- bodies (MAbs) and further characterized the binding reactivity of these antibodies (via enzyme-linked immunosorbent assay) to a range of purified virus and recombinant protein substrates. The H10-directed MAbs displayed functional hemagglutination inhibition (HI) and neutralization activity, and the N8-directed antibodies displayed functional neuraminidase inhibition (NI) activity against H10N8. Surprisingly, the HI-reactive H10 antibodies, as well as a previously generated, group 2 hemagglutinin (HA) stalk-reactive antibody, demonstrated NI activity against H10N8 and an H10N7 strain; this phenomenon was absent when virus was treated with detergent, suggesting the anti-HA antibodies inhibited neuraminidase enzymatic activity through steric hindrance. We tested the prophylactic efficacy of one representative H10-reactive, N8-reactive, and group 2 HA stalk-reactive http://jvi.asm.org/ antibody in vivo using a BALB/c challenge model. All three antibodies were protective at a high dose (5 mg/kg). -
Inhibition of HIV-1 by an Anti-Integrase Single-Chain Variable
Gene Therapy (1999) 6, 660–666 1999 Stockton Press All rights reserved 0969-7128/99 $12.00 http://www.stockton-press.co.uk/gt Inhibition of HIV-1 by an anti-integrase single-chain variable fragment (SFv): delivery by SV40 provides durable protection against HIV-1 and does not require selection M BouHamdan1, L-X Duan1, RJ Pomerantz1 and DS Strayer1,2 1The Dorrance H Hamilton Laboratories, Center for Human Virology, Division of Infectious Diseases, Department of Medicine; and 2Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA Human immunodeficiency virus type I (HIV-1) encodes the SFv-IN was confirmed by Western blotting and several proteins that are packaged into virus particles. Inte- immunofluorescence staining, which showed that Ͼ90% of grase (IN) is an essential retroviral enzyme, which has SupT1 T-lymphocytic cells treated with SV(Aw) expressed been a target for developing agents to inhibit virus repli- the SFv-IN protein without selection. When challenged, cation. In previous studies, we showed that intracellular HIV-1 replication, as measured by HIV-1 p24 antigen expression of single-chain variable antibody fragments expression and syncytium formation, was potently inhibited (SFvs) that bind IN, delivered via retroviral expression vec- in cells expressing SV40-delivered SFv-IN. Levels of inhi- tors, provided resistance to productive HIV-1 infection in bition of HIV-1 infection achieved using this approach were T-lymphocytic cells. In the current studies, we evaluated comparable to those achieved using murine leukemia virus simian-virus 40 (SV40) as a delivery vehicle for anti-IN (MLV) as a transduction vector, the major difference being therapy of HIV-1 infection. -
The Role of F-Box Proteins During Viral Infection
Int. J. Mol. Sci. 2013, 14, 4030-4049; doi:10.3390/ijms14024030 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Review The Role of F-Box Proteins during Viral Infection Régis Lopes Correa 1, Fernanda Prieto Bruckner 2, Renan de Souza Cascardo 1,2 and Poliane Alfenas-Zerbini 2,* 1 Department of Genetics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-970, Brazil; E-Mails: [email protected] (R.L.C.); [email protected] (R.S.C.) 2 Department of Microbiology/BIOAGRO, Federal University of Viçosa, Viçosa, MG 36570-000, Brazil; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +55-31-3899-2955; Fax: +55-31-3899-2864. Received: 23 October 2012; in revised form: 14 December 2012 / Accepted: 17 January 2013 / Published: 18 February 2013 Abstract: The F-box domain is a protein structural motif of about 50 amino acids that mediates protein–protein interactions. The F-box protein is one of the four components of the SCF (SKp1, Cullin, F-box protein) complex, which mediates ubiquitination of proteins targeted for degradation by the proteasome, playing an essential role in many cellular processes. Several discoveries have been made on the use of the ubiquitin–proteasome system by viruses of several families to complete their infection cycle. On the other hand, F-box proteins can be used in the defense response by the host. This review describes the role of F-box proteins and the use of the ubiquitin–proteasome system in virus–host interactions. -
Modulation of NF-Κb Signalling by Microbial Pathogens
REVIEWS Modulation of NF‑κB signalling by microbial pathogens Masmudur M. Rahman and Grant McFadden Abstract | The nuclear factor-κB (NF‑κB) family of transcription factors plays a central part in the host response to infection by microbial pathogens, by orchestrating the innate and acquired host immune responses. The NF‑κB proteins are activated by diverse signalling pathways that originate from many different cellular receptors and sensors. Many successful pathogens have acquired sophisticated mechanisms to regulate the NF‑κB signalling pathways by deploying subversive proteins or hijacking the host signalling molecules. Here, we describe the mechanisms by which viruses and bacteria micromanage the host NF‑κB signalling circuitry to favour the continued survival of the pathogen. The nuclear factor-κB (NF-κB) family of transcription Signalling targets upstream of NF‑κB factors regulates the expression of hundreds of genes that NF-κB proteins are tightly regulated in both the cyto- are associated with diverse cellular processes, such as pro- plasm and the nucleus6. Under normal physiological liferation, differentiation and death, as well as innate and conditions, NF‑κB complexes remain inactive in the adaptive immune responses. The mammalian NF‑κB cytoplasm through a direct interaction with proteins proteins are members of the Rel domain-containing pro- of the inhibitor of NF-κB (IκB) family, including IκBα, tein family: RELA (also known as p65), RELB, c‑REL, IκBβ and IκBε (also known as NF-κBIα, NF-κBIβ and the NF-κB p105 subunit (also known as NF‑κB1; which NF-κBIε, respectively); IκB proteins mask the nuclear is cleaved into the p50 subunit) and the NF-κB p100 localization domains in the NF‑κB complex, thus subunit (also known as NF‑κB2; which is cleaved into retaining the transcription complex in the cytoplasm. -
PP2A-Dependent Disruption of Centrosome Replication and Cytoskeleton Organization in Drosophila by SV40 Small Tumor Antigen
Oncogene (2008) 27, 6334–6346 & 2008 Macmillan Publishers Limited All rights reserved 0950-9232/08 $32.00 www.nature.com/onc ORIGINAL ARTICLE PP2A-dependent disruption of centrosome replication and cytoskeleton organization in Drosophila by SV40 small tumor antigen S Kotadia1,LRKao1, SA Comerford2, RT Jones1, RE Hammer3 and TL Megraw1 1Department of Pharmacology, The Cecil and Ida Green Center for Reproductive Biology Sciences, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA; 2Department of Molecular Genetics, The Cecil and Ida Green Center for Reproductive Biology Sciences, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA and 3Department of Biochemistry, The Cecil and Ida Green Center for Reproductive Biology Sciences, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA Viruses of the DNA tumor virus family share the ability to cell-cycle and apoptosis regulation, viral oncoproteins transform vertebrate cells through the action of virus- transform cells. Investigation of DNA tumor virus encoded tumor antigens that interfere with normal cell oncoproteins has led to the identification of many physiology. They accomplish this very efficiently by fundamental mechanisms of tumor suppression (Lavia inhibiting endogenous tumor suppressor proteins that et al., 2003; Ahuja et al., 2005). By altering the activity control cell proliferation and apoptosis. Simian virus 40 of p53, retinoblastoma protein and serine/threonine (SV40) encodes two oncoproteins, large tumor antigen, protein phosphatase 2A (PP2A), three key tumor which directly inhibits the tumor suppressors p53 and Rb, suppressors, SV40 can cause tumor formation in and small tumor antigen (ST), which interferes with transgenic mouse models (Ahuja et al., 2005; Arroyo serine/threonine protein phosphatase 2A (PP2A). -
The Simian Virus 40 Large Tumor Antigen Activates Csrc and Requires Csrc for Full Neoplastic Transformation
ANTICANCER RESEARCH 30: 47-54 (2010) The Simian Virus 40 Large Tumor Antigen Activates cSrc and Requires cSrc for Full Neoplastic Transformation ROZANNE ARULANANDAM, MULU GELETU and LEDA RAPTIS Departments of Microbiology and Immunology and Pathology, Queen's University, Kingston, Ontario, K7L 3N6, Canada Abstract. Aim: To investigate the role of the cellular The effects of TAg on the Rb family proteins are thought to be protooncogene product, cSrc, in neoplastic transformation by exerted by regulating the activity of the E2F transcription factors. the large tumor antigen of simian virus 40 (TAg), the ability of There are eight known E2F proteins (E2F1-8), all of which TAg to increase cSrc activity was examined. Materials and possess a DNA-binding domain that governs their interactions Methods: cSrc activity was measured in cells expressing wild- with a common consensus sequence present in the promoters of type or mutant TAg and compared to the parental line. Results: a number of genes (reviewed in (4, 5)). In quiescent cells, E2F- The results indicated that TAg expression in mouse 3T3 regulated genes are not expressed because their promoters are fibroblasts causes a dramatic increase in cSrc activity, a finding occupied primarily by p130/E2F4 complexes which repress which establishes TAg as a cSrc activator. This ability transcription. Following receptor stimulation, Rb proteins are depended upon a TAg, intact retinoblastoma-susceptibility gene inactivated through phosphorylation by the cyclin-dependent product (Rb) family-binding site. In addition, genetic ablation kinases and this results in the replacement of the p130/E2F4 of pRb in mouse fibroblasts increased cSrc activity, suggesting complexes by the ‘activating’ E2F1-3. -
Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma
International Journal of Molecular Sciences Article Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma Chang-Kyu Heo 1, Hai-Min Hwang 1, Won-Hee Lim 1,2, Hye-Jung Lee 3, Jong-Shin Yoo 4, Kook-Jin Lim 3 and Eun-Wie Cho 1,2,* 1 Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea; [email protected] (C.-K.H.); [email protected] (H.-M.H.); [email protected] (W.-H.L.) 2 Department of Functional Genomics, University of Science and Technology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea 3 ProteomeTech Inc. 401, Yangcheon-ro, Gangseo-gu, Seoul 07528, Korea; [email protected] (H.-J.L.); [email protected] (K.-J.L.) 4 Biomedical Omics Group, Korea Basic Science Institute, 162 YeonGuDanji-Ro, Ochang-eup, Cheongju, Chungbuk 28119, Korea; [email protected] * Correspondence: [email protected]; Tel.: +82-42-860-4155 Received: 12 November 2020; Accepted: 16 December 2020; Published: 19 December 2020 Abstract: Tumor-associated (TA) autoantibodies have been identified at the early tumor stage before developing clinical symptoms, which holds hope for early cancer diagnosis. We identified a TA autoantibody from HBx-transgenic (HBx-tg) hepatocellular carcinoma (HCC) model mouse, characterized its target antigen, and examined its relationship to human HCC. The mimotopes corresponding to the antigenic epitope of TA autoantibody were screened from a random cyclic peptide library and used for the detection of serum TA autoantibody. The target antigen of the TA autoantibody was identified as an oncogenic bi-functional purine biosynthesis protein, ATIC. -
Expression of Hbx and COX-2 in Chronic Hepatitis B, Cirrhosis and Hepatocellular Carcinoma: Implication of Hbx in Upregulation of COX-2
Modern Pathology (2004) 17, 1169–1179 & 2004 USCAP, Inc All rights reserved 0893-3952/04 $30.00 www.modernpathology.org Expression of HBx and COX-2 in chronic hepatitis B, cirrhosis and hepatocellular carcinoma: implication of HBx in upregulation of COX-2 Alfred S-L Cheng1, Henry L-Y Chan1, Wai K Leung1,KaFTo2, Minnie Y-Y Go1, John Y-H Chan3, Choong T Liew2 and Joseph J-Y Sung1 1Department of Medicine & Therapeutics; 2Department of Anatomical & Cellular Pathology and 3Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong Hepatitis B virus is a major etiological factor of hepatocellular carcinoma, but the underlying mechanisms remain unclear. We have previously demonstrated that upregulation of cyclooxygenase (COX)-2 in chronic hepatitis B persisted despite successful antiviral therapy. In this study, we investigated the relationship between the transactivator HBx and COX-2 in hepatitis B virus-associated chronic liver diseases. Expressions of HBx and COX-2 in tissue specimens were determined by single and double immunohistochemistry. The effects of HBx on COX-2 and prostaglandin E2 production were studied by transfection. HBx was expressed in 11/11 (100%) of chronic hepatitis B, 23/23 (100%) of cirrhosis, and 18/23 (78%) of hepatocellular carcinoma, whereas no immunoreactivity was found in four nonalcoholic steato-hepatitis controls. COX-2 expression was also detected in all specimens of liver lesions except in only 29% of poorly differentiated hepatocellular carcinoma. Significant correlation between HBx and COX-2 immunoreactivity scores was found in different types of chronic liver diseases (chronic hepatitis B, rs ¼ 0.68; cirrhosis, rs ¼ 0.57; hepatocellular carcinoma, rs ¼ 0.45). -
Identification of Rab18 As an Essential Host Factor for Bkpyv Infection Using a Whole Genome RNA 2 Interference Screen
bioRxiv preprint doi: https://doi.org/10.1101/157602; this version posted June 29, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Identification of Rab18 as an Essential Host Factor for BKPyV Infection Using a Whole Genome RNA 2 Interference Screen 3 4 Linbo Zhaoa, Michael J. Imperialea,b,* 5 6 aDepartment of Microbiology and Immunology, bComprehensive Cancer Center, University of Michigan, 7 Ann Arbor, MI, 48109, USA 8 9 10 11 12 13 14 15 16 17 18 * Corresponding author. Department of Microbiology and Immunology, 1150 West Medical Center 19 Drive, 5724 Medical Science II, Ann Arbor, MI 48109-5620, USA. Tel. +1 (734) 763 9162. Fax: +1 (734) 20 764 3562. 21 E-mail addresses: [email protected] (L. Zhao); [email protected] (M.J. Imperiale). 22 23 24 1 bioRxiv preprint doi: https://doi.org/10.1101/157602; this version posted June 29, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 25 Abstract 26 27 BK polyomavirus (BKPyV) is a human pathogen first isolated in 1971. BKPyV infection is ubiquitous in the 28 human population, with over 80% of adults worldwide being seropositive for BKPyV. BKPyV infection is 29 usually asymptomatic; however, BKPyV reactivation in immunosuppressed transplant patients causes 30 two diseases, polyomavirus-associated nephropathy and hemorrhagic cystitis.