Viruses, Cells, and Diseases (CIOC5125Q)
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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. -
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. -
DNA Recombination Is Sufficient for Retroviral Transduction JODY R
Proc. Natl. Acad. Sci. USA Vol. 92, pp. 2460-2464, March 1995 Biochemistry DNA recombination is sufficient for retroviral transduction JODY R. SCHWARTZ, Susi DUESBERG, AND PETER H. DUESBERG Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3206 Contributed by Peter H. Duesberg, November 28, 1994 ABSTRACT Oncogenic retroviruses carry coding se- quences that are transduced from cellular protooncogenes. Nat- env pOl X ural transduction involves two nonhomologous recombinations and is thus extremely rare. Since transduction has never been reproduced experimentall, its mechanism has been studied in terms oftwoehypotheses: (i) the DNAmodel,which postulates two ___ _-I ____ DNA recombinations, and (ii) the RNA model, which postulates a 5' DNA recombination and a 3' RNA recombination occurring during reverse transcription of viral and protooncogene RNA. proto-onc gene Here we use two viral DNA constructs to test the prediction ofthe DNA model that the 3' DNA recombination is achieved by conventional integration of a retroviral DNA 3' of the chromo- somal protooncogene coding region. For the DNA model to be ga-onc - gag viable, such recombinant viruses must be infectious without the w5 essential tract that precedes the 3' purportedly polypurine (ppt) FIG. 1. The DNA model of retroviral transduction. The model long terminal repeat (LTR) of all retroviruses. Our constructs proposes that the 5' retrovirus/protooncogene junction is achieved by consist ofa ras coding region from Harvey sarcoma virus which nonhomologous recombination between a circular provirus with a is naturally linked at the 5' end to a retroviral LTR and single LTR. Such proviruses are common in virus-infected cells (1). -
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. -
The LUCA and Its Complex Virome in Another Recent Synthesis, We Examined the Origins of the Replication and Structural Mart Krupovic , Valerian V
PERSPECTIVES archaea that form several distinct, seemingly unrelated groups16–18. The LUCA and its complex virome In another recent synthesis, we examined the origins of the replication and structural Mart Krupovic , Valerian V. Dolja and Eugene V. Koonin modules of viruses and posited a ‘chimeric’ scenario of virus evolution19. Under this Abstract | The last universal cellular ancestor (LUCA) is the most recent population model, the replication machineries of each of of organisms from which all cellular life on Earth descends. The reconstruction of the four realms derive from the primordial the genome and phenotype of the LUCA is a major challenge in evolutionary pool of genetic elements, whereas the major biology. Given that all life forms are associated with viruses and/or other mobile virion structural proteins were acquired genetic elements, there is no doubt that the LUCA was a host to viruses. Here, by from cellular hosts at different stages of evolution giving rise to bona fide viruses. projecting back in time using the extant distribution of viruses across the two In this Perspective article, we combine primary domains of life, bacteria and archaea, and tracing the evolutionary this recent work with observations on the histories of some key virus genes, we attempt a reconstruction of the LUCA virome. host ranges of viruses in each of the four Even a conservative version of this reconstruction suggests a remarkably complex realms, along with deeper reconstructions virome that already included the main groups of extant viruses of bacteria and of virus evolution, to tentatively infer archaea. We further present evidence of extensive virus evolution antedating the the composition of the virome of the last universal cellular ancestor (LUCA; also LUCA. -
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. -
Naturally Occurring Polymorphisms of the Mouse Gammaretrovirus Receptors CAT-1 and XPR1 Alter Virus Tropism and Pathogenicity
Hindawi Publishing Corporation Advances in Virology Volume 2011, Article ID 975801, 16 pages doi:10.1155/2011/975801 Review Article Naturally Occurring Polymorphisms of the Mouse Gammaretrovirus Receptors CAT-1 and XPR1 Alter Virus Tropism and Pathogenicity Christine A. Kozak Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-0460, USA Correspondence should be addressed to Christine A. Kozak, [email protected] Received 5 May 2011; Accepted 12 July 2011 Academic Editor: Paul Jolicoeur Copyright © 2011 Christine A. Kozak. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Gammaretroviruses of several different host range subgroups have been isolated from laboratory mice. The ecotropic viruses infect mouse cells and rely on the host CAT-1 receptor. The xenotropic/polytropic viruses, and the related human-derived XMRV, can infect cells of other mammalian species and use the XPR1 receptor for entry. The coevolution of these viruses and their receptors in infected mouse populations provides a good example of how genetic conflicts can drive diversifying selection. Genetic and epigenetic variations in the virus envelope glycoproteins can result in altered host range and pathogenicity, and changes in the virus binding sites of the receptors are responsible for host restrictions that reduce virus entry or block it altogether. These battleground regions are marked by mutational changes that have produced 2 functionally distinct variants of the CAT-1 receptor and 5 variants of the XPR1 receptor in mice, as well as a diverse set of infectious viruses, and several endogenous retroviruses coopted by the host to interfere with entry. -
Proviruses with Long-Term Stable Expression Accumulate In
viruses Article Proviruses with Long-Term Stable Expression Accumulate in Transcriptionally Active Chromatin Close to the Gene Regulatory Elements: Comparison of ASLV-, HIV- and MLV-Derived Vectors Dalibor Miklík 1,2, Filip Šenigl 1 and Jiˇrí Hejnar 1,* 1 Institute of Molecular Genetics, Czech Academy of Sciences, Videnska 1083, CZ-14220 Prague 4, Czech Republic; [email protected] (D.M.); [email protected] (F.S.) 2 Faculty of Science, Charles University, Albertov 6, CZ-12843 Prague 2, Czech Republic * Correspondence: [email protected] Received: 29 January 2018; Accepted: 6 March 2018; Published: 8 March 2018 Abstract: Individual groups of retroviruses and retroviral vectors differ in their integration site preference and interaction with the host genome. Hence, immediately after infection genome-wide distribution of integrated proviruses is non-random. During long-term in vitro or persistent in vivo infection, the genomic position and chromatin environment of the provirus affects its transcriptional activity. Thus, a selection of long-term stably expressed proviruses and elimination of proviruses, which have been gradually silenced by epigenetic mechanisms, helps in the identification of genomic compartments permissive for proviral transcription. We compare here the extent and time course of provirus silencing in single cell clones of the K562 human myeloid lymphoblastoma cell line that have been infected with retroviral reporter vectors derived from avian sarcoma/leukosis virus (ASLV), human immunodeficiency virus type 1 (HIV) and murine leukaemia virus (MLV). While MLV proviruses remain transcriptionally active, ASLV proviruses are prone to rapid silencing. The HIV provirus displays gradual silencing only after an extended time period in culture. -
Frequent Provirus Insertional Mutagenesis of Notchl in Thymomas of MMTVD/Myc Transgenic Mice Suggests a Collaboration of C-Myc and Notctil for Oncogenesis
Downloaded from genesdev.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Frequent provirus insertional mutagenesis of Notchl in thymomas of MMTVD/myc transgenic mice suggests a collaboration of c-myc and Notctil for oncogenesis Luc Girard, l Zaher Hanna, 1,2 Normand Beaulieu, 1 Caroline D. Hoemann, 1 Carole Simard, 1 Christine A. Kozak, 3 and Paul Jolicoeur 1'4'5"6 1Laboratory of Molecular Biology, Clinical Research Institute of Montr4al, Montr4al, Qu~bec, Canada H2W 1R7; 2D4partement de Mddecine et de 4 Microbiologie et d'Immunologie, Universit~ de Montr4al, Montreal, Quebec, Canada H3J 3J7; 3National Institute of Allergy and Infectious Diseases (NIAIDI, National Institutes of Health, Bethesda, Maryland 20892, USA; SDepartment of Experimental Medicine, McGill University, Montr4al, Quebec, Canada, H3G-1A4 The MMTVD/myc transgenic mice spontaneously develop oligoclonal CD4+CD8 + T-ceU tumors. We used provirus insertional mutagenesis in these mice to identify putative collaborators of c-myc. We found that Notchl was mutated in a high proportion (52%) of these tumors. Proviruses were inserted upstream of the exon coding for the transmembrane domain and in both transcriptional orientations. These mutations led to high expression of truncated Notchl RNAs and proteins (86-110 kD). In addition, many Notchl-rearranged tumors showed elevated levels of full-length Notchl transcripts, whereas nearly all showed increased levels of full-length (330-kD) or close to full-length (280-kD) Notchl proteins. The 5' end of the truncated RNAs were determined for some tumors by use of RT-PCR and 5' RACE techniques. Depending on the orientation of the proviruses, viral LTR or cryptic promoters appeared to be utilized, and coding potential began in most cases in the transmembrane domain. -
Koala Retrovirus in Free-Ranging Populations—Prevalence
The Koala and its Retroviruses: Implications for Sustainability and Survival edited by Geoffrey W. Pye, Rebecca N. Johnson, and Alex D. Greenwood Preface .................................................................... Pye, Johnson, & Greenwood 1 A novel exogenous retrovirus ...................................................................... Eiden 3 KoRV and other endogenous retroviruses ............................. Roca & Greenwood 5 Molecular biology and evolution of KoRV ............................. Greenwood & Roca 11 Prevalence of KoRV ............................. Meers, Simmons, Jones, Clarke, & Young 15 Disease in wild koalas ............................................................... Hanger & Loader 19 Origins and impact of KoRV ........................................ Simmons, Meers, Clarke, Young, Jones, Hanger, Loader, & McKee 31 Koala immunology .......................................................... Higgins, Lau, & Maher 35 Disease in captive Australian koalas ........................................................... Gillett 39 Molecular characterization of KoRV ..................................................... Miyazawa 47 European zoo-based koalas ........................................................................ Mulot 51 KoRV in North American zoos ......................................... Pye, Zheng, & Switzer 55 Disease at the genomic level ........................................................................... Neil 57 Koala retrovirus variants ........................................................................... -
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.