NCI/Tufts University
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Non-Primate Lentiviral Vectors and Their Applications in Gene Therapy for Ocular Disorders
viruses Review Non-Primate Lentiviral Vectors and Their Applications in Gene Therapy for Ocular Disorders Vincenzo Cavalieri 1,2,* ID , Elena Baiamonte 3 and Melania Lo Iacono 3 1 Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze Edificio 16, 90128 Palermo, Italy 2 Advanced Technologies Network (ATeN) Center, University of Palermo, Viale delle Scienze Edificio 18, 90128 Palermo, Italy 3 Campus of Haematology Franco e Piera Cutino, Villa Sofia-Cervello Hospital, 90146 Palermo, Italy; [email protected] (E.B.); [email protected] (M.L.I.) * Correspondence: [email protected] Received: 30 April 2018; Accepted: 7 June 2018; Published: 9 June 2018 Abstract: Lentiviruses have a number of molecular features in common, starting with the ability to integrate their genetic material into the genome of non-dividing infected cells. A peculiar property of non-primate lentiviruses consists in their incapability to infect and induce diseases in humans, thus providing the main rationale for deriving biologically safe lentiviral vectors for gene therapy applications. In this review, we first give an overview of non-primate lentiviruses, highlighting their common and distinctive molecular characteristics together with key concepts in the molecular biology of lentiviruses. We next examine the bioengineering strategies leading to the conversion of lentiviruses into recombinant lentiviral vectors, discussing their potential clinical applications in ophthalmological research. Finally, we highlight the invaluable role of animal organisms, including the emerging zebrafish model, in ocular gene therapy based on non-primate lentiviral vectors and in ophthalmology research and vision science in general. Keywords: FIV; EIAV; BIV; JDV; VMV; CAEV; lentiviral vector; gene therapy; ophthalmology; zebrafish 1. -
An Overview of the Molecular Phylogeny of Lentiviruses
Phylogeny of Lentiviruses 35 An overview of the molecular Reviews phylogeny of lentiviruses Brian T. Foley T10, MS K710, Los Alamos National Laboratory, Los Alamos, NM 87545 Introduction Lentiviruses are one of several groups of retroviruses. In early studies of the molecular phylogenetic analysis of endogenous and exogenous retroviruses it was suggested that the retroviruses could be divided into four groups, two complex with several accessory or regulatory genes (lentiviruses; and the bovine and primate leukemia virus group now known as deltaretrovirus) and two simple, with just the gag, pol and env genes and few or no accessory genes (a group including spumaretroviruses, C-type endogenous retroviruses and MMLV; the other group including Rous Sarcoma virus, HERV-K Simian Retrovirus 1 and MMTV) [1–5]. A more recent study, including many more recently discovered exogenous and endogenous retroviruses, illustrates the diversity of retroviruses [6]. The retroviridae are currently officially classified into seven different genera, according to the Seventh Report of the International Committee on Taxonomy of Viruses, 2000 (http://www.ncbi.nlm.nih.gov/ICTV). The seven genera are named alpha through epsilon retroviruses plus lentiviruses and spumaviruses. Phylogenetic trees based on pol gene sequences can be found in several recent papers[6–8]. None of the retroviruses in either group of complex retroviruses have been found in an endogenous state to date. Within the Lentiviruses, the primate lentiviruses discovered to date form a monophyletic cluster (Figure 1). One notable difference between the primate lentiviruses and the non-primate lentiviruses is that all nonprimate lentiviruses, except the BIV/JDV lineage, contain a region of the pol gene encoding a dUTPase, whereas all primate lentiviruses lack this region of pol. -
Guide for Common Viral Diseases of Animals in Louisiana
Sampling and Testing Guide for Common Viral Diseases of Animals in Louisiana Please click on the species of interest: Cattle Deer and Small Ruminants The Louisiana Animal Swine Disease Diagnostic Horses Laboratory Dogs A service unit of the LSU School of Veterinary Medicine Adapted from Murphy, F.A., et al, Veterinary Virology, 3rd ed. Cats Academic Press, 1999. Compiled by Rob Poston Multi-species: Rabiesvirus DCN LADDL Guide for Common Viral Diseases v. B2 1 Cattle Please click on the principle system involvement Generalized viral diseases Respiratory viral diseases Enteric viral diseases Reproductive/neonatal viral diseases Viral infections affecting the skin Back to the Beginning DCN LADDL Guide for Common Viral Diseases v. B2 2 Deer and Small Ruminants Please click on the principle system involvement Generalized viral disease Respiratory viral disease Enteric viral diseases Reproductive/neonatal viral diseases Viral infections affecting the skin Back to the Beginning DCN LADDL Guide for Common Viral Diseases v. B2 3 Swine Please click on the principle system involvement Generalized viral diseases Respiratory viral diseases Enteric viral diseases Reproductive/neonatal viral diseases Viral infections affecting the skin Back to the Beginning DCN LADDL Guide for Common Viral Diseases v. B2 4 Horses Please click on the principle system involvement Generalized viral diseases Neurological viral diseases Respiratory viral diseases Enteric viral diseases Abortifacient/neonatal viral diseases Viral infections affecting the skin Back to the Beginning DCN LADDL Guide for Common Viral Diseases v. B2 5 Dogs Please click on the principle system involvement Generalized viral diseases Respiratory viral diseases Enteric viral diseases Reproductive/neonatal viral diseases Back to the Beginning DCN LADDL Guide for Common Viral Diseases v. -
LENTIVIRUS and LENTIVIRAL VECTORS
LENTIVIRUS and LENTIVIRAL VECTORS Risk Group: 3 I. Background and Health Hazards Lentiviruses are a subset of retroviruses that have the ability to integrate into host chromosomes and to infect non-dividing cells, and include human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) which can infect humans. Another commonly used lentivirus that is infectious to animals, but not humans, is feline immunodeficiency virus (FIV). Lentiviral vectors consist of recombinant or synthetic nucleic acid sequences and HIV or other lentivirus- based viral packaging and regulatory sequences flanked by either wild-type or chimeric long terminal repeat (LTR) regions. Use of these vector systems is particularly desirable because of their ability to integrate transgenes into dividing, as well as, non-dividing cells. However, there are risks associated with working with lentiviral vectors and these must be carefully evaluated. The two major risks are: 1) the potential generation of replication competent lentivirus (RCL); and 2) the potential for oncogenesis. These risks are largely based upon the vector system used and the transgene insert encoded by the vector. Therefore, it is imperative that prior to utilizing a lentiviral vector system, a risk assessment must be reviewed and documented. Also, because construction and/or use of lentiviral vectors falls under the definition of r/sNA research as outlined in the NIH Guidelines, possession must be reported in the workplace’s biological agent inventory and experiments must be submitted for review and approval by the site IBC prior to initiation. II. MODES OF TRANSMISSION Lentivirus is transmissible through injection, ingestion, exposure to broken skin or contact with mucous membranes of the eyes, nose and mouth. -
The Expression of Human Endogenous Retroviruses Is Modulated by the Tat Protein of HIV‐1
The Expression of Human Endogenous Retroviruses is modulated by the Tat protein of HIV‐1 by Marta Jeannette Gonzalez‐Hernandez A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Immunology) in The University of Michigan 2012 Doctoral Committee Professor David M. Markovitz, Chair Professor Gary Huffnagle Professor Michael J. Imperiale Associate Professor David J. Miller Assistant Professor Akira Ono Assistant Professor Christiane E. Wobus © Marta Jeannette Gonzalez‐Hernandez 2012 For my family and friends, the most fantastic teachers I have ever had. ii Acknowledgements First, and foremost, I would like to thank David Markovitz for his patience and his scientific and mentoring endeavor. My time in the laboratory has been an honor and a pleasure. Special thanks are also due to all the members of the Markovitz laboratory, past and present. It has been a privilege, and a lot of fun, to work near such excellent scientists and friends. You all have a special place in my heart. I would like to thank all the members of my thesis committee for all the valuable advice, help and jokes whenever needed. Our collaborators from the Bioinformatics Core, particularly James Cavalcoli, Fan Meng, Manhong Dai, Maureen Sartor and Gil Omenn gave generous support, technical expertise and scientific insight to a very important part of this project. Thank you. Thanks also go to Mariana Kaplan’s and Akira Ono’s laboratory for help with experimental designs and for being especially generous with time and reagents. iii Table of Contents Dedication ............................................................................................................................ ii Acknowledgements ............................................................................................................. iii List of Figures ................................................................................................................... -
HIV 101: Pathogenesis and Treatment
HIV 101: Pathogenesis and Treatment Stephen Raffanti MD MPH Professor of Medicine Vanderbilt University School of Medicine . Dr. Raffanti has no financial disclosures to make. Objectives . After this presentation the attendee should be able to: . Describe current issues in the epidemiology of the HIV epidemic. Describe the life cycle of HIV; . Describe the way that HIV interacts with its host, producing disease. Describe the principles of treatment. Describe Acute HIV infection . Describe the initial evaluation of an HIV infected patient Testing, linkage to care, effective treatment and effective PrEP could stop the epidemic today. Percentages of Diagnoses of HIV Infection among Adults and Adolescents, by Region and Population of Area of Residence, 2015—United States Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. Data for the year 2015 are preliminary and based on 6 months reporting delay. Data exclude persons whose county of residence is unknown. Percentages of Diagnoses of HIV Infection among Adults and Adolescents, by Population of Area of Residence and Age at Diagnosis, 2015—United States Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. Data for the year 2015 are preliminary and based on 6 months reporting delay. Data exclude persons whose county of residence is unknown. Diagnoses of HIV Infection among Men Who Have Sex with Men, by Age Group, 2010–2014—United States and 6 Dependent Areas Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays and missing transmission category, but not for incomplete reporting. -
Enhancement of Antitumor Activity of Gammaretrovirus Carrying IL-12
Cancer Gene Therapy (2010) 17, 37–48 r 2010 Nature Publishing Group All rights reserved 0929-1903/10 $32.00 www.nature.com/cgt ORIGINAL ARTICLE Enhancement of antitumor activity of gammaretrovirus carrying IL-12 gene through genetic modification of envelope targeting HER2 receptor: a promising strategy for bladder cancer therapy Y-S Tsai1,2,3, A-L Shiau1,4, Y-F Chen4, H-T Tsai3, T-S Tzai3 and C-L Wu1,5 1Institute of Clinical Medicine, National Cheng Kung University Medical College, Tainan, Taiwan; 2Department of Urology, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan; 3Department of Urology, National Cheng Kung University Medical College, Tainan, Taiwan; 4Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan and 5Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, Tainan, Taiwan The objective of this study was to develop an HER2-targeted, envelope-modified Moloney murine leukemia virus (MoMLV)-based gammaretroviral vector carrying interleukin (IL)-12 gene for bladder cancer therapy. It displayed a chimeric envelope protein containing a single-chain variable fragment (scFv) antibody to the HER2 receptor and carried the mouse IL-12 gene. The fragment of anti-erbB2scFv was constructed into the proline-rich region of the viral envelope of the packaging vector lacking a transmembrane subunit of the carboxyl terminal region of surface subunit. As compared with envelope-unmodified gammaretroviruses, envelope- modified ones -
Toll-Like Receptor and Cytokine Responses to Infection with Endogenous and Exogenous Koala Retrovirus, and Vaccination As a Control Strategy
Review Toll-Like Receptor and Cytokine Responses to Infection with Endogenous and Exogenous Koala Retrovirus, and Vaccination as a Control Strategy Mohammad Enamul Hoque Kayesh 1,2 , Md Abul Hashem 1,3,4 and Kyoko Tsukiyama-Kohara 1,4,* 1 Transboundary Animal Diseases Centre, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan; [email protected] (M.E.H.K.); [email protected] (M.A.H.) 2 Department of Microbiology and Public Health, Faculty of Animal Science and Veterinary Medicine, Patuakhali Science and Technology University, Barishal 8210, Bangladesh 3 Department of Health, Chattogram City Corporation, Chattogram 4000, Bangladesh 4 Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan * Correspondence: [email protected]; Tel.: +81-99-285-3589 Abstract: Koala populations are currently declining and under threat from koala retrovirus (KoRV) infection both in the wild and in captivity. KoRV is assumed to cause immunosuppression and neoplastic diseases, favoring chlamydiosis in koalas. Currently, 10 KoRV subtypes have been identified, including an endogenous subtype (KoRV-A) and nine exogenous subtypes (KoRV-B to KoRV-J). The host’s immune response acts as a safeguard against pathogens. Therefore, a proper understanding of the immune response mechanisms against infection is of great importance for Citation: Kayesh, M.E.H.; Hashem, the host’s survival, as well as for the development of therapeutic and prophylactic interventions. M.A.; Tsukiyama-Kohara, K. Toll-Like A vaccine is an important protective as well as being a therapeutic tool against infectious disease, Receptor and Cytokine Responses to Infection with Endogenous and and several studies have shown promise for the development of an effective vaccine against KoRV. -
Lentivirus Vector Fact Sheet
LENTIVIRUS VECTOR FACT SHEET LENTIVIRUSES: Lentiviral vector constructs are derived from HIV and are therefore highly efficient vehicles for in vivo gene delivery. Use of these vector systems is particularly desirable because of their ability to integrate transgenes into dividing, as well as, non-dividing cells. However, there are risks associated with working with lentiviral vectors and these must be carefully evaluated. The two major risks are: 1) the potential generation of replication competent virus; and 2) the potential for oncogenesis through insertional mutagenesis. These risks are largely based upon the vector system used and the transgene insert encoded by the vector. Therefore, it is imperative that prior to utilizing a lentiviral vector system, a risk assessment must be completed and documented. Also, because construction and/or use of lentiviral vectors falls under the definition of rDNA research as outlined in the NIH Recombinant DNA Guidelines, possession must be reported in the workplace’s biological agent inventory and experiments must be submitted for review and approval by the site IBC prior to initiation. Typically, lentiviral vectors may be safely handled using either BSL-2 or BSL-2 enhanced controls depending upon the risk assessment. LENTIVIRAL VECTORS: Lentiviruses can infect not only dividing, but also non-dividing host cells, because their pre-integration complex (virus “shell”) can get through the intact membrane of the nucleus of the target cell. Lentiviral vectors can be used to provide highly effective gene therapy as they can provide long-term expression of the vectored transgene in target cells. First-generation lentiviral vectors were manufactured using a single vector packaging system that contained all HIV genes, except the envelope (env) gene, in one plasmid. -
VMC 321: Systematic Veterinary Virology Retroviridae Retro: from Latin Retro,"Backwards”
VMC 321: Systematic Veterinary Virology Retroviridae Retro: from Latin retro,"backwards” - refers to the activity of reverse RETROVIRIDAE transcriptase and the transfer of genetic information from RNA to DNA. Retroviruses Viral RNA Viral DNA Viral mRNA, genome (integrated into host genome) Reverse (retro) transfer of genetic information Usually, well adapted to their hosts Endogenous retroviruses • RNA viruses • single stranded, positive sense, enveloped, icosahedral. • Distinguished from all other RNA viruses by presence of an unusual enzyme, reverse transcriptase. Retroviruses • Retro = reversal • RNA is serving as a template for DNA synthesis. • One genera of veterinary interest • Alpharetrovirus • • Family - Retroviridae • Subfamily - Orthoretrovirinae [Ortho: from Greek orthos"straight" • Genus -. Alpharetrovirus • Genus - Betaretrovirus Family- • Genus - Gammaretrovirus • Genus - Deltaretrovirus Retroviridae • Genus - Lentivirus [ Lenti: from Latin lentus, "slow“ ]. • Genus - Epsilonretrovirus • Subfamily - Spumaretrovirinae • Genus - Spumavirus Retroviridae • Subfamily • Orthoretrovirinae • Genus • Alpharetrovirus Alpharetrovirus • Species • Avian leukosis virus(ALV) • Rous sarcoma virus (RSV) • Avian myeloblastosis virus (AMV) • Fujinami sarcoma virus (FuSV) • ALVs have been divided into 10 envelope subgroups - A , B, C, D, E, F, G, H, I & J based on • host range Avian • receptor interference patterns • neutralization by antibodies leukosis- • subgroup A to E viruses have been divided into two groups sarcoma • Noncytopathic (A, C, and E) • Cytopathic (B and D) virus (ALV) • Cytopathic ALVs can cause a transient cytotoxicity in 30- 40% of the infected cells 1. The viral envelope formed from host cell membrane; contains 72 spiked knobs. 2. These consist of a transmembrane protein TM (gp 41), which is linked to surface protein SU (gp 120) that binds to a cell receptor during infection. 3. The virion has cone-shaped, icosahedral core, Structure containing the major capsid protein 4. -
Effects of Retroviruses on Host Genome Function
ANRV361-GE42-20 ARI 1 August 2008 18:2 V I E E W R S I E N C N A D V A Effects of Retroviruses on Host Genome Function Patric Jern and John M. Coffin Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111; email: [email protected], John.Coffi[email protected] Annu. Rev. Genet. 2008. 42:20.1–20.23 Key Words The Annual Review of Genetics is online at Human Endogenous Retrovirus, LTR, transcription, recombination, genet.annualreviews.org methylation This article’s doi: 10.1146/annurev.genet.42.110807.091501 Abstract Copyright c 2008 by Annual Reviews. For millions of years, retroviral infections have challenged vertebrates, All rights reserved occasionally leading to germline integration and inheritance as ERVs, 0066-4197/08/1201-0001$20.00 genetic parasites whose remnants today constitute some 7% to 8% of the human genome. Although they have had significant evolutionary side effects, it is useful to view ERVs as fossil representatives of retro- viruses extant at the time of their insertion into the germline, not as direct players in the evolutionary process itself. Expression of particu- lar ERVs is associated with several positive physiological functions as well as certain diseases, although their roles in human disease as etio- logical agents, possible contributing factors, or disease markers—well demonstrated in animal models—remain to be established. Here we discuss ERV contributions to host genome structure and function, in- cluding their ability to mediate recombination, and physiological effects on the host transcriptome resulting from their integration, expression, and other events. -
Protocol and Reagents for Pseudotyping Lentiviral Particles with SARS-Cov-2 Spike Protein for Neutralization Assays
bioRxiv preprint doi: https://doi.org/10.1101/2020.04.20.051219; this version posted April 20, 2020. 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 4.0 International license. 1 of 15 Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 Spike protein for neutralization assays Katharine H.D. Crawford 1,2,3, Rachel Eguia 1, Adam S. Dingens 1, Andrea N. Loes 1, Keara D. Malone 1, Caitlin R. Wolf 4, Helen Y. Chu 4, M. Alejandra Tortorici 5,6, David Veesler 5, Michael Murphy 7, Deleah Pettie 7, Neil P. King 5,7, Alejandro B. Balazs 8, and Jesse D. Bloom 1,2,9,* 1 Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; [email protected] (K.D.C.), [email protected] (R.E.), [email protected] (A.S.D.), [email protected] (K.M.), [email protected] (A.N.L.) 2 Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA 3 Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA 4 Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98195, USA; [email protected] (C.R.W.), [email protected] (H.Y.C.) 5 Department of Biochemistry, University of Washington, Seattle, WA 98109, USA; [email protected] (M.A.T.), [email protected] (D.V.), [email protected] (M.M.), [email protected] (D.P.), [email protected] (N.P.K.) 6 Institute