Gp160 / HIV-Targeted Library
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Herpes Simplex Virus Type 1 Oril Is Not Required for Virus Infection In
JOURNAL OF VIROLOGY, Nov. 1987, p. 3528-3535 Vol. 61, No. 11 0022-538X/87/113528-08$02.00/0 Copyright C 1987, American Society for Microbiology Herpes Simplex Virus Type 1 oriL Is Not Required for Virus Replication or for the Establishment and Reactivation of Latent Infection in Mice MARYELLEN POLVINO-BODNAR, PAULO K. ORBERG, AND PRISCILLA A. SCHAFFER* Laboratory of Tumor Virus Genetics, Dana-Farber Cancer Institute, and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115 Received 11 May 1987/Accepted 31 July 1987 During the course of experiments designed to isolate deletion mutants of herpes simplex virus type 1 in the gene encoding the major DNA-binding protein, ICP8, a mutant, d61, that grew efficiently in ICP8-expressing Vero cells but not in normal Vero cells was isolated (P. K. Orberg and P. A. Schaffer, J. Virol. 61:1136-1146, 1987). d61 was derived by cotransfection of ICP8-expressing Vero cells with infectious wild-type viral DNA and a plasmid, pDX, that contains an engineered 780-base-pair (bp) deletion in the ICP8 gene, as well as a spontaneous -55-bp deletion in OriL. Gel electrophoresis and Southern blot analysis indicated that d61 DNA carried both deletions present in pDX. The ability of d61 to replicate despite the deletion in OriL suggested that a functional OriL is not essential for virus replication in vitro. Because d61 harbored two mutations, a second mutant, ts+7, with a deletion in oriL-associated sequences and an intact ICP8 gene was constructed. Both d61 and ts+7 replicated efficiently in their respective permissive host cells, although their yields were slightly lower than those of control viruses with intact oriL sequences. -
Topological Analysis of the Gp41 MPER on Lipid Bilayers Relevant to the Metastable HIV-1 Envelope Prefusion State
Topological analysis of the gp41 MPER on lipid bilayers relevant to the metastable HIV-1 envelope prefusion state Yi Wanga,b, Pavanjeet Kaurc,d, Zhen-Yu J. Sune,1, Mostafa A. Elbahnasawya,b,2, Zahra Hayatic,d, Zhi-Song Qiaoa,b,3, Nhat N. Buic, Camila Chilea,b,4, Mahmoud L. Nasre,5, Gerhard Wagnere, Jia-Huai Wanga,f, Likai Songc, Ellis L. Reinherza,b,6, and Mikyung Kima,g,6 aLaboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115; bDepartment of Medicine, Harvard Medical School, Boston, MA 02115; cNational High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32306; dDepartment of Physics, Florida State University, Tallahassee, FL 32306; eDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115; fDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215; and gDepartment of Dermatology, Harvard Medical School, Boston, MA 02215 Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved September 23, 2019 (received for review July 18, 2019) The membrane proximal external region (MPER) of HIV-1 envelope immunologically vulnerable epitopes targeted by several of the most glycoprotein (gp) 41 is an attractive vaccine target for elicitation of broadly neutralizing antibodies (bNAbs) developed during the broadly neutralizing antibodies (bNAbs) by vaccination. However, course of natural HIV-1 infection (10–13). Insertion, deletion, current details regarding the quaternary structural organization of and mutations of residues in the MPER defined the functional the MPER within the native prefusion trimer [(gp120/41)3] are elu- importance of the MPER in Env incorporation, viral fusion, and sive and even contradictory, hindering rational MPER immunogen infectivity (14–16). -
Viroporins: Structures and Functions Beyond Cell Membrane Permeabilization
Editorial Viroporins: Structures and Functions beyond Cell Membrane Permeabilization José Luis Nieva 1,* and Luis Carrasco 2,* Received: 17 September 2015 ; Accepted: 21 September 2015 ; Published: 29 September 2015 Academic Editor: Eric O. Freed 1 Biophysics Unit (CSIC, UPV/EHU) and Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao, Spain 2 Centro de Biología Molecular Severo Ochoa (CSIC, UAM), c/Nicolás Cabrera, 1, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain * Correspondence: [email protected] (J.L.N.); [email protected] (L.C.); Tel.: +34-94-601-3353 (J.L.N.); +34-91-497-8450 (L.C.) Viroporins represent an interesting group of viral proteins that exhibit two sets of functions. First, they participate in several viral processes that are necessary for efficient production of virus progeny. Besides, viroporins interfere with a number of cellular functions, thus contributing to viral cytopathogenicity. Twenty years have elapsed from the first review on viroporins [1]; since then several reviews have covered the advances on viroporin structure and functioning [2–8]. This Special Issue updates and revises new emerging roles of viroporins, highlighting their potential use as antiviral targets and in vaccine development. Viroporin structure. Viroporins are usually short proteins with at least one hydrophobic amphipathic helix. Homo-oligomerization is achieved by helix–helix interactions in membranes rendering higher order structures, forming aqueous pores. Progress in viroporin structures during the last 2–3 years has in some instances provided a detailed knowledge of their functional architecture, including the fine definition of binding sites for effective inhibitors. -
Patent Document US 06872395
I 1111111111111111 11111 111111111111111 1111111111 1111111111 lll111111111111111 US006872395B2 (12) United States Patent (10) Patent No.: US 6,872,395 B2 Kawaoka (45) Date of Patent: Mar.29,2005 (54) VIRUSES COMPRISING MUTANT ION Mena, I., et al., "Rescue of a Synthetic Choramphenicol CHANNEL PROTEIN Acetyltransferase RNA into influenza Virus-Like Particles obtained from recombinant plasmids", J. of Virology, vol. (75) Inventor: Yoshihiro Kawaoka, Madison, WI 70, No. 8, XP002150091, 5016-5024, (Aug. 1996). (US) Neumann, G., et al., "Generation of influenza A Viruses entirely from cloned cDNAs", Proc. of the Nat'l Aca. of (73) Assignee: Wisconsin Alumni Research Sciences, USA, vol. 96, XP002150093, 9345-9350, (Aug. Foundation, Madison, WI (US) 1999). ( *) Notice: Subject to any disclaimer, the term of this Neumann, G., et al., "Plasmid-Driven Formation of Influ patent is extended or adjusted under 35 enza Virus-Like Particles", J. of Virology, vol. 74, No. 1, U.S.C. 154(b) by O days. XP002150094, 547-551, (Jan. 2000). Neumann, G., et al., "RNA Polymerase I-Mediated Expres sion of Influenza Viral RNA Molecules", Virology, vol. 202, (21) Appl. No.: 09/834,095 No. 1, XP000952667, 477-479, (Jul. 1994). (22) Filed: Apr. 12, 2001 Neirynck, S., et al., "A universal influenza A vaccine based on the extracellular domain of the M2 protein", Nature (65) Prior Publication Data Medicine, 5 (10), pp. 1157-1163, (Oct. 1999). US 2003/0194694 Al Oct. 16, 2003 Piller, S. C., et al., "Vpr protein of human immunodeficiency virus type 1 forms cation-selective channels in planar lipid Related U.S. Application Data bilayers", PNAS, 93, pp. -
How Influenza Virus Uses Host Cell Pathways During Uncoating
cells Review How Influenza Virus Uses Host Cell Pathways during Uncoating Etori Aguiar Moreira 1 , Yohei Yamauchi 2 and Patrick Matthias 1,3,* 1 Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; [email protected] 2 Faculty of Life Sciences, School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK; [email protected] 3 Faculty of Sciences, University of Basel, 4031 Basel, Switzerland * Correspondence: [email protected] Abstract: Influenza is a zoonotic respiratory disease of major public health interest due to its pan- demic potential, and a threat to animals and the human population. The influenza A virus genome consists of eight single-stranded RNA segments sequestered within a protein capsid and a lipid bilayer envelope. During host cell entry, cellular cues contribute to viral conformational changes that promote critical events such as fusion with late endosomes, capsid uncoating and viral genome release into the cytosol. In this focused review, we concisely describe the virus infection cycle and highlight the recent findings of host cell pathways and cytosolic proteins that assist influenza uncoating during host cell entry. Keywords: influenza; capsid uncoating; HDAC6; ubiquitin; EPS8; TNPO1; pandemic; M1; virus– host interaction Citation: Moreira, E.A.; Yamauchi, Y.; Matthias, P. How Influenza Virus Uses Host Cell Pathways during 1. Introduction Uncoating. Cells 2021, 10, 1722. Viruses are microscopic parasites that, unable to self-replicate, subvert a host cell https://doi.org/10.3390/ for their replication and propagation. Despite their apparent simplicity, they can cause cells10071722 severe diseases and even pose pandemic threats [1–3]. -
Assembly Lecture 11 Biology W3310/4310 Virology Spring 2014
Assembly Lecture 11 Biology W3310/4310 Virology Spring 2014 “Anatomy is des.ny.” --SIGMUND FREUD All virions complete a common set of assembly reac3ons * common to all viruses common to many viruses ©Principles of Virology, ASM Press The structure of a virus parcle determines how it is formed ©Principles of Virology, ASM Press Assembly is dependent on host cell machinery • Cellular chaperones • Transport systems • Secretory pathway • Nuclear import and export machinery Concentrang components for assembly: Nothing happens fast in dilute solu1ons • Viral components oSen visible by light microscopy (‘factories’ or ‘inclusions’) • Concentrate proteins on internal membranes (poliovirus) • Negri bodies (rabies virus) Viral proteins have ‘addresses’ built into their structure • Membrane targeYng: Signal sequences, fa\y acid modificaons • Membrane retenYon signals • Nuclear localizaYon sequences (NLS) • Nuclear export signals 414 Localiza3on of viral proteins to the nucleus CHAPTER 12 Golgi apparatus Ribosome Rough endoplasmic reticulum Plasma membrane Py(VP1) + VP2/3 Ad hexon + 5 100 kDa Nuclear envelope: Outer nuclear membrane Inner nuclear membrane Nucleus Nuclear pore complex Mitochondrion Cytoskeleton: Influenza virus NP Intermediate filament Microtubule Actin filament bundle Extracellular matrix ©Principles of Virology, ASM Press Figure 12.1 Localization of viral proteins to the nucleus. The nucleus and major membrane-bound compartments of the cytoplasm, as well as components of the cytoskeleton, are illustrated schematically and not to scale. Viral proteins destined for the nucleus are synthesized by cytoplasmic polyribosomes, as illustrated for the infl uenza virus NP protein. They engage with the cytoplasmic face of the nuclear pore complex and are translocated into the nucleus by the protein import machinery of the host cell. -
The Hepatitis C Virus P7 Protein Forms an Ion Channel That Is Inhibited by Long-Alkyl-Chain Iminosugar Derivatives
The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives Davor Pavlovic´*, David C. A. Neville*, Olivier Argaud*, Baruch Blumberg†, Raymond A. Dwek*, Wolfgang B. Fischer*, and Nicole Zitzmann*‡ *Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom; and †Fox Chase Cancer Center, Philadelphia, PA 19111 Contributed by Baruch Blumberg, March 17, 2003 We show that hepatitis C virus (HCV) p7 protein forms ion channels data have been obtained by introducing mutations into an in black lipid membranes. HCV p7 ion channels are inhibited by infectious cDNA clone of BVDV. An in-frame deletion of the long-alkyl-chain iminosugar derivatives, which have antiviral ac- entire p7 does not affect RNA replication but leads to the tivity against the HCV surrogate bovine viral diarrhea virus. HCV p7 production of noninfectious virions. However, infective viral presents a potential target for antiviral therapy. particles can be generated by complementing p7 in trans (9), which suggests that the pestivirus p7 is essential for the epatitis C virus (HCV) is the major cause of chronic production of infective progeny virus. Interestingly, noninfec- Hhepatitis with a significant risk of end-stage liver cirrhosis tive BVDV particles also are created by treatment with and hepatocellular carcinoma (1). HCV belongs to the family long-alkyl-chain iminosugar derivatives (3). Flaviviridae, which consists of three genera: flaviviruses, pesti- Recently, HCV p7 has been shown to be a polytopic mem- viruses, and hepaciviruses. In the absence of both a suitable small brane protein that crosses the membrane twice and has its N and animal model and a reliable in vitro infectivity assay for HCV, C termini oriented toward the extracellular environment (10). -
Ube1a Suppresses Herpes Simplex Virus-1 Replication
viruses Article UBE1a Suppresses Herpes Simplex Virus-1 Replication Marina Ikeda 1 , Akihiro Ito 2, Yuichi Sekine 1 and Masahiro Fujimuro 1,* 1 Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan; [email protected] (M.I.); [email protected] (Y.S.) 2 Laboratory of Cell Signaling, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan; [email protected] * Correspondence: [email protected]; Tel.: +81-75-595-4717 Academic Editors: Magdalena Weidner-Glunde and Andrea Lipi´nska Received: 7 November 2020; Accepted: 1 December 2020; Published: 4 December 2020 Abstract: Herpes simplex virus-1 (HSV-1) is the causative agent of cold sores, keratitis, meningitis, and encephalitis. HSV-1-encoded ICP5, the major capsid protein, is essential for capsid assembly during viral replication. Ubiquitination is a post-translational modification that plays a critical role in the regulation of cellular events such as proteasomal degradation, protein trafficking, and the antiviral response and viral events such as the establishment of infection and viral replication. Ub-activating enzyme (E1, also named UBE1) is involved in the first step in the ubiquitination. However, it is still unknown whether UBE1 contributes to viral infection or the cellular antiviral response. Here, we found that UBE1a suppressed HSV-1 replication and contributed to the antiviral response. The UBE1a inhibitor PYR-41 increased HSV-1 production. Immunofluorescence analysis revealed that UBE1a highly expressing cells presented low ICP5 expression, and vice versa. UBE1a inhibition by PYR-41 and shRNA increased ICP5 expression in HSV-1-infected cells. -
Lentivirus and Lentiviral Vectors Fact Sheet
Lentivirus and Lentiviral Vectors Family: Retroviridae Genus: Lentivirus Enveloped Size: ~ 80 - 120 nm in diameter Genome: Two copies of positive-sense ssRNA inside a conical capsid Risk Group: 2 Lentivirus Characteristics Lentivirus (lente-, latin for “slow”) is a group of retroviruses characterized for a long incubation period. They are classified into five serogroups according to the vertebrate hosts they infect: bovine, equine, feline, ovine/caprine and primate. Some examples of lentiviruses are Human (HIV), Simian (SIV) and Feline (FIV) Immunodeficiency Viruses. Lentiviruses can deliver large amounts of genetic information into the DNA of host cells and can integrate in both dividing and non- dividing cells. The viral genome is passed onto daughter cells during division, making it one of the most efficient gene delivery vectors. Most lentiviral vectors are based on the Human Immunodeficiency Virus (HIV), which will be used as a model of lentiviral vector in this fact sheet. Structure of the HIV Virus The structure of HIV is different from that of other retroviruses. HIV is roughly spherical with a diameter of ~120 nm. HIV is composed of two copies of positive ssRNA that code for nine genes enclosed by a conical capsid containing 2,000 copies of the p24 protein. The ssRNA is tightly bound to nucleocapsid proteins, p7, and enzymes needed for the development of the virion: reverse transcriptase (RT), proteases (PR), ribonuclease and integrase (IN). A matrix composed of p17 surrounds the capsid ensuring the integrity of the virion. This, in turn, is surrounded by an envelope composed of two layers of phospholipids taken from the membrane of a human cell when a newly formed virus particle buds from the cell. -
Vpr Mediates Immune Evasion and HIV-1 Spread by David R. Collins A
Vpr mediates immune evasion and HIV-1 spread by David R. Collins A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Microbiology and Immunology) in the University of Michigan 2015 Doctoral Committee: Professor Kathleen L. Collins, Chair Professor David M. Markovitz Associate Professor Akira Ono Professor Alice Telesnitsky © David R. Collins ________________________________ All Rights Reserved 2015 Dedication In loving memory of Sullivan James and Aiko Rin ii Acknowledgements I am very grateful to my mentor, Dr. Kathleen L. Collins, for providing excellent scientific training and guidance and for directing very exciting and important research. I am in the debt of my fellow Collins laboratory members, present and former, for their daily support, encouragement and assistance. In particular, I am thankful to Dr. Michael Mashiba for pioneering our laboratory’s investigation of Vpr, which laid the framework for this dissertation, and for key contributions to Chapter II and Appendix. I am grateful to Jay Lubow and Dr. Zana Lukic for their collaboration and contributions to ongoing work related to this dissertation. I also thank the members of my thesis committee, Dr. Akira Ono, Dr. Alice Telesnitsky, and Dr. David Markovitz for their scientific and professional guidance. Finally, this work would not have been possible without the unwavering love and support of my family, especially my wife Kali and our wonderful feline companions Ayumi, Sully and Aiko, for whom I continue to endure life’s -
HSV-1 Single-Cell Analysis Reveals the Activation of Anti-Viral And
RESEARCH ARTICLE HSV-1 single-cell analysis reveals the activation of anti-viral and developmental programs in distinct sub-populations Nir Drayman1,2*, Parthiv Patel1,2, Luke Vistain1,2, Savas¸Tay1,2* 1Institute for Molecular Engineering, The University of Chicago, Chicago, United States; 2Institute for Genomics and Systems Biology, The University of Chicago, Chicago, United States Abstract Viral infection is usually studied at the population level by averaging over millions of cells. However, infection at the single-cell level is highly heterogeneous, with most infected cells giving rise to no or few viral progeny while some cells produce thousands. Analysis of Herpes Simplex virus 1 (HSV-1) infection by population-averaged measurements has taught us a lot about the course of viral infection, but has also produced contradictory results, such as the concurrent activation and inhibition of type I interferon signaling during infection. Here, we combine live-cell imaging and single-cell RNA sequencing to characterize viral and host transcriptional heterogeneity during HSV-1 infection of primary human cells. We find extreme variability in the level of viral gene expression among individually infected cells and show that these cells cluster into transcriptionally distinct sub-populations. We find that anti-viral signaling is initiated in a rare group of abortively infected cells, while highly infected cells undergo cellular reprogramming to an embryonic-like transcriptional state. This reprogramming involves the recruitment of b-catenin to the host nucleus and viral replication compartments, and is required for late viral gene expression and progeny production. These findings uncover the transcriptional differences in cells with variable infection outcomes and shed new light on the manipulation of host pathways by HSV-1. -
HIV-1) CD4 Receptor and Its Central Role in Promotion of HIV-1 Infection
MICROBIOLOGICAL REVIEWS, Mar. 1995, p. 63–93 Vol. 59, No. 1 0146-0749/95/$04.0010 Copyright q 1995, American Society for Microbiology The Human Immunodeficiency Virus Type 1 (HIV-1) CD4 Receptor and Its Central Role in Promotion of HIV-1 Infection STEPHANE BOUR,* ROMAS GELEZIUNAS,† AND MARK A. WAINBERG* McGill AIDS Centre, Lady Davis Institute-Jewish General Hospital, and Departments of Microbiology and Medicine, McGill University, Montreal, Quebec, Canada H3T 1E2 INTRODUCTION .........................................................................................................................................................63 RETROVIRAL RECEPTORS .....................................................................................................................................64 Receptors for Animal Retroviruses ........................................................................................................................64 CD4 Is the Major Receptor for HIV-1 Infection..................................................................................................65 ROLE OF THE CD4 CORECEPTOR IN T-CELL ACTIVATION........................................................................65 Structural Features of the CD4 Coreceptor..........................................................................................................65 Interactions of CD4 with Class II MHC Determinants ......................................................................................66 CD4–T-Cell Receptor Interactions during T-Cell Activation