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3 results on '"Département de Virologie - Department of Virology"'

1. DNA topoisomerase 1 represses HIV-1 promoter activity through its interaction with a guanine quadruplex present in the LTR sequence

Author

Lista, María José, Jousset, Anne-Caroline, Cheng, Mingpan, Saint-André, Violaine, Perrot, Elouan, Rodrigues, Melissa, Di Primo, Carmelo, Gadelle, Danielle, Toccafondi, Elenia, Segeral, Emmanuel, Berlioz-Torrent, Clarisse, Emiliani, Stéphane, Mergny, Jean-Louis, Lavigne, Marc, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Département de Virologie - Department of Virology, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and This work was supported by Sidaction [AO 2017-2 and AO 2020-1 to ML], the ANRS [AO 2014-2 CSS2 and AO 2019-1 CSS11 to ML]. MJL is a recipient of an ANRS postdoctoral fellowship. ACJ, EP and MR are recipients of Research Engineer or Technician contracts from Sidaction.

Subjects
Transcriptional regulation, HIV-1 LTR promoter, DNA topoisomerases, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, HIV-1 transcription, HIV-1 latency, Guanine quadruplex, Host-virus interaction
Abstract

Background: Once integrated in the genome of infected cells, HIV-1 provirus is transcribed by the cellular transcription machinery. This process is regulated by both viral and cellular factors, which are necessary for an efficient viral replication as well as for the setting up of viral latency, leading to a repressed transcription of the integrated provirus.Results: In this study, we examined the role of two parameters in HIV-1 LTR promoter activity. We identified DNA topoisomerase1 (TOP1) to be a potent repressor of this promoter and linked this repression to its catalytic domain. Additionally, we confirmed the folding of a Guanine quadruplex (G4) structure in the HIV-1 promoter and its repressive effect. We demonstrated a direct interaction between TOP1 and this G4 structure, providing evidence of a functional relationship between the two repressive elements. Mutations abolishing G4 folding affected TOP1/G4 interaction and hindered G4-dependent inhibition of TOP1 catalytic activity in vitro. As a result, HIV-1 promoter activity was reactivated in a native chromatin environment. Lastly, we noticed an enrichment of predicted G4 sequences in the promoter of TOP1-repressed cellular genes.Conclusions: Our results demonstrate the formation of a TOP1/G4 complex on the HIV-1 LTR promoter and its repressive effect on the promoter activity. They reveal the existence of a new mechanism of TOP1/G4-dependent transcriptional repression conserved between viral and human genes. This mechanism contrasts with the known property of TOP1 as global transcriptional activator and offers new perspectives for anti-cancer and anti-viral strategies.

Published
2023
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2. APOBEC3C S188I Polymorphism Enhances Context-Specific Editing of Hepatitis B Virus Genome

Author

Pierre Khalfi, Rodolphe Suspène, Vincent Caval, Valérie Thiers, Guillaume Beauclair, Agnès Marchio, Claudine Bekondi, Marie Amougou Atsama, Serge Magloire Camengo-Police, Dominique Noah Noah, Richard Njouom, Hervé Blanc, Thomas Vallet, Marco Vignuzzi, Pascal Pineau, Jean Pierre Vartanian, Virologie (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Département de Virologie - Department of Virology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP), Centre Pasteur du Cameroun, Hôpital Central de Yaoundé [Yaoundé], Hôpital de l'Amitié [Bangui], Populations virales et Pathogenèse - Viral Populations and Pathogenesis, This work was supported by the Institut Pasteur (grants to R. S., V. C., V. T., G. B., H. B., T. V., M. V., and J. P. V.), Institut Pasteur International Network (Action Concertée Inter-Pasteurienne grant number 17-2010 and Grant Dedonder to C. B., M. A. A., S. M. C. P., D. N. N., and R. N.), and and Ligue Contre le Cancer (Equipe Labélisée d’Anne Dejean to A. M. and P. P.). P. K. was supported by the Ligue Contre le Cancer.

Subjects
Hepatitis B virus, editing, nucleotide context, Genome, Viral, Hepatitis B, Polymorphism, Single Nucleotide, patients, polymorphism, Infectious Diseases, Cytidine Deaminase, Africa, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, APOBEC3C, Immunology and Allergy
Abstract

Single-nucleotide polymorphism in APOBEC3C (resulting in a serine to isoleucine in position 188) is present in approximately 10% of African populations and greatly enhances restriction against human immunodeficiency virus-1 and simian immunodeficiency virus by improving dimerization and DNA processivity of the enzyme. In this study, we demonstrated in culture and in infected patients that hepatitis B virus (HBV) could be edited by APOBEC3CS188I. Using next-generation sequencing, we demonstrated that APOBEC3CS188I led to enhanced editing activity in 5ʹTpCpA→5ʹTpTpA context. This constitutes a new hallmark of this enzyme, which could be used to determine its impact on HBV or nuclear DNA.

Published
2022
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3. Genomic epidemiology of SARS-CoV-2 in Cambodia, January 2020 to February 2021

Author

Yvonne C F Su, Jordan Z J Ma, Tey Putita Ou, Leakhena Pum, Sidonn Krang, Philomena Raftery, Michael H Kinzer, Jennifer Bohl, Vanra Ieng, Vannda Kab, Sarika Patel, Borann Sar, Wong Foong Ying, Jayanthi Jayakumar, Viseth Srey Horm, Narjis Boukli, Sokhoun Yann, Cecile Troupin, Vireak Heang, Jose A Garcia-Rivera, Yi Sengdoeurn, Seng Heng, Sreyngim Lay, Sophana Chea, Chau Darapheak, Chin Savuth, Asheena Khalakdina, Sowath Ly, Laurence Baril, Jessica E Manning, Etienne Simone-Loriere, Veasna Duong, Philippe Dussart, Ly Sovann, Gavin J D Smith, Erik A Karlsson, Duke-NUS Medical School [Singapore], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Université de Montpellier (UM), Ministry of Health [Phnom Penh], World Health Organization [Phnom Penh] (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centers for Disease Control and Prevention [Phnom Penh], Embassy of the United States of America, National Institute of Allergy and Infectious Diseases [Phnom Penh, Cambodia] (NIAID), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), US Naval Medical Research Unit n°2, National Institute of Public Health [Phnom Penh, Cambodge], Département de Virologie - Department of Virology, Institut Pasteur [Paris] (IP), Duke University [Durham], The work at Institut Pasteur du Cambodge is supported by the WHO, the European Union, The Pasteur International Center for Research on Emerging Infectious Diseases National Institutes of Health, Department of Health and Human Services funded project No. 1U01AI151758-01, Wellcome Trust grant 222574/Z/21/Z, the British Embassy in Cambodia, and French Development Agency-funded ECOnomic development, ECOsystem MOdifications, and emerging infectious diseases Risk Evaluation (ECOMORE) 2 COVID-19 top up project No. CZZ 2146 01A. E.A.K. was funded, in part, by federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services Contract No. 75N93021C00015. The study was supported by the Duke-NUS Signature Research Programme funded by the Ministry of Health, Singapore, and by contracts HHSN272201400006C and 75N93021C00016 from the National Institute of Allergy and Infectious Disease, National Institutes of Health, Department of Health and Human Services, USA. This work was funded in part by the Division of Intramural Research at National Institute of Allergy and Infectious Diseases at the National Institutes of Health and Bill and Melinda Gates Foundation Grant OPP1211806. E.S.L. acknowledges funding from the INCEPTION programme (Investissements d’Avenir), grant number ANR-16-CONV-0005., and ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016)

Subjects
pandemic, [SDV]Life Sciences [q-bio], Virology, coronavirus, COVID-19, genetic diversity, phylogeny, Microbiology
Abstract

The first case of coronavirus disease 2019 (COVID-19) in Cambodia was confirmed on 27 January 2020 in a traveller from Wuhan. Cambodia subsequently implemented strict travel restrictions, and although intermittent cases were reported during the first year of the COVID-19 pandemic, no apparent widespread community transmission was detected. Investigating the routes of severe acute respiratory coronavirus 2 (SARS-CoV-2) introduction into the country was critical for evaluating the implementation of public health interventions and assessing the effectiveness of social control measures. Genomic sequencing technologies have enabled rapid detection and monitoring of emerging variants of SARS-CoV-2. Here, we detected 478 confirmed COVID-19 cases in Cambodia between 27 January 2020 and 14 February 2021, 81.3 per cent in imported cases. Among them, fifty-four SARS-CoV-2 genomes were sequenced and analysed along with representative global lineages. Despite the low number of confirmed cases, we found a high diversity of Cambodian viruses that belonged to at least seventeen distinct PANGO lineages. Phylogenetic inference of SARS-CoV-2 revealed that the genetic diversity of Cambodian viruses resulted from multiple independent introductions from diverse regions, predominantly, Eastern Asia, Europe, and Southeast Asia. Most cases were quickly isolated, limiting community spread, although there was an A.23.1 variant cluster in Phnom Penh in November 2020 that resulted in a small-scale local transmission. The overall low incidence of COVID-19 infections suggests that Cambodia’s early containment strategies, including travel restrictions, aggressive testing and strict quarantine measures, were effective in preventing large community outbreaks of COVID-19.

Published
2022
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