Biological Sciences
Lentivirus
Lentivirus is a type of retrovirus known for its ability to cause long-term infections in its host. It is characterized by its ability to integrate its genetic material into the DNA of the host cell, allowing it to persist and replicate. Lentiviruses have been extensively studied and are used as vectors in gene therapy and research applications.
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8 Key excerpts on "Lentivirus"
eBook - ePubHealth of HIV Infected People
Food, Nutrition and Lifestyle without Antiretroviral Drugs
- Ronald Ross Watson(Author)
- 2015(Publication Date)
- Academic Press(Publisher)
The purpose of this work is to elucidate useful relationships between human immunodeficiency virus (HIV)-related Lentiviruses in nonhuman species and HIV. In particular, this study examined relationships between simian immunodeficiency virus (SIV), feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV), and HIV. The need to investigate these Lentiviruses is due to the current global prevalence of HIV and demand for better therapeutic strategies and understanding of available models for this disease. To clarify common characteristics between these viruses, this chapter explores areas such as nutritional effects, morphology, genomic organization and expression, modes of transmission, infectious cycles, and clinical and pathological characteristics of these Lentiviruses. This study found that several HIV-related Lentiviruses have proven to be useful models for studying HIV pathology as well as disease treatments and possible preventative strategies. Further research of these Lentiviruses could provide more beneficial correlations with HIV.Keywords
Retroviruses; Lentiviruses; human immunodeficiency virus; simian immunodeficiency virus; feline immunodeficiency virus; bovine immunodeficiency virus20.1 Introduction
Lentiviruses are a genus of retroviruses (family Retroviridae ) that infect several mammalian species, including humans. Although most commonly known for the human immunodeficiency virus (HIV), this genus includes several other Lentiviruses that trigger serious persistent and chronic infections in their hosts [1 ,2] . Since the discovery of HIV-induced acquired immunodeficiency syndrome (AIDS) in the 1980s, there has been a substantial increase in the amount of research focused on HIV infections in humans, along with related viral infections in nonhuman animals [2] . In-depth characterizations of Lentiviruses and host interactions across a range of biological scales have been established in a number of mammalian species [2] . Such Lentiviruses include HIV, simian immunodeficiency virus (SIV), feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV), maedivisna virus (MVV), equine infectious anemia virus (EIAV), Jembrana disease virus (JDV), and caprine arthritis–encephalitis virus (CAEV). Currently, there are no known animal model systems that reproduce the entire infectious process of HIV from viral entrance to manifestations of the disease. However, there are a number of lentiviral infections in nonhuman species that do reproduce one or more of the characteristic events of HIV infections [3]
eBook - PDF- Shailendra K. Saxena(Author)
- 2016(Publication Date)
- IntechOpen(Publisher)
Section 1 Retrovirus - Molecular Biology and Pathogenesis Chapter 1 Molecular Biology and Pathogenesis of Retroviruses Shailendra K. Saxena and Sai V. Chitti Additional information is available at the end of the chapter http://dx.doi.org/10.5772/62885 Abstract Retroviruses consist of a varied family of enveloped RNA viruses with positive-sense RNAs that replicate in a host cell through the process of reverse transcription. Retrovirus‐ es belong to the Retroviridae family that typically carries their genetic material in the form of ribonucleic acid, while the genetic material of their hosts is in the form of deoxy‐ ribonucleic acid. Infections with a number of retroviruses can lead to serious conditions, such as AIDS, a range of malignancies, neurological diseases, and added clinical condi‐ tions. In addition, some can even become integrated as DNA in the germ line and passed as endogenous viruses from generation to generation. Surprisingly, retroviruses do not appear to straightforwardly activate host innate defenses. On the other hand, attention in these viruses extends beyond their disease causing capabilities. For example, studies on the retroviruses led to the discovery of oncogenes, understanding of mechanisms that regulate eukaryotic gene expression, and these are proving to be valuable research tools in molecular biology and have been used successfully in gene therapy. The central goals of retrovirology today are the treatment and the prevention of human and non-human diseases and to use this virus in research. Keywords: retrovirus, Retroviridae, reverse transcriptase, replication, immune responses, ART 1. Introduction During the past few decades retrovirus has done an adequate amount of harm to the human life and became a big threat globally.
eBook - ePub- S.C. Makrides(Author)
- 2003(Publication Date)
- Elsevier Science(Publisher)
Virus-based vectors for gene expression in mammalian cells: LentivirusesAbstract Publisher SummaryMehdi Gasmi1 , Flossie Wong-Staal2, * 11 Ceregene, Inc., 9381 Judicial Drive #130, San Diego, CA 92121, USA. Tel.: +1 (858) 458-8828; Fax: +1 (858) 458-88012 Department of Medicine MS0665, University of California San Diego, La Jolla, CA 92093, USAE-mail address: [email protected]Lentiviruses, represented by the human immunodeficiency virus type 1 (HIV-1) are retroviruses that possess complex genomes and a finely regulated mode of replication. These viruses share the common feature of being able to infect post-mitotic cells of the monocyte/macrophage lineage; a phenomenon closely related to their biology and induced pathologies. Gene therapy vectors based on Lentiviruses enable the generation of a gene delivery system that combines features of vectors derived from murine oncoretroviruses (i.e., large coding capacity and stable integration of the transgene into host-cell genetic material) and the capability of transducing non-dividing cells. As such, vectors derived from HIV-1 have been designed and the proof of principle of stable transgene delivery in non-dividing cells has been established in a wide variety of systems. The major hurdle that prevents the progression of the HIV-1-based vector system to the clinic for evaluation of therapeutic potential is the association of the parental virus with an incurable and still largely fatal disease in humans. An alternative approach to the construction of HIV-1-derived vectors, is the use of viruses derived from less pathogenic human immunodeficiency virus type 2 (HIV-2) and from simian immunodeficiency virus (SIV). Non-primate lentiviral vector systems derived from feline immunodeficiency virus (FIV), equine infectious anemia virus (EIAV), and visna/maedi virus (VMV) have also been described in the chapter. However, the impressive achievements accomplished with HIV-1-based vectors have largely overshadowed the characterization of these other lentiviral vector systems. Therefore, this chapter focuses on HIV-1 derived vectors to exemplify the basic design and improvements relevant to the development of a safe and efficient Lentivirus-based gene delivery system.
eBook - PDFAdvanced Textbook On Gene Transfer, Gene Therapy And Genetic Pharmacology: Principles, Delivery And Pharmacological And Biomedical Applications Of Nucleotide-based Therapies
Principles, Delivery and Pharmacological and Biomedical Applications of Nucleotide-Based Therapies
- Daniel Scherman(Author)
- 2013(Publication Date)
- ICP(Publisher)
PART II VECTORS AND GENE DELIVERY TECHNIQUES This page intentionally left blank This page intentionally left blank 117 8 γ -RETROVIRUS- AND Lentivirus-DERIVED VECTORS FOR GENE TRANSFER AND THERAPY Caroline Duros a and Odile Cohen-Haguenauer a,b 8.1 Introduction Viral vectors can be manipulated in vitro to modify their genomes in order to insert a gene of interest. Intrinsic viral cycle properties, such as DNA importation into the nucleus and its expression, are therefore used to deliver the transgene to target cells. The major advantage of viral vectors derived from retroviruses is the integration of the transferred transgene into the chromosome of the host cell, which may enable long-lasting transgene expression, not only in the transduced target cell, but also in all offspring cells after cell division. 8.2 The Concept: Designing Retrovirus-Based Vectors 8.2.1 Starting From the Knowledge of Helper Retrovirus Biology Retroviruses are composed of oncoviruses, Lentiviruses and spumaviruses. Oncoretroviruses can only infect dividing cells, because they require the disrup-tion of the nuclear membrane for the viral genome to get into the nucleus, whereas Lentiviruses can also infect non-dividing cells. Oncoretroviruses and Lentiviruses a Laboratory of Biotechnology and Applied Pharmacogenetics, CNRS UMR8 H3, Ecole Normale Supérieure de Cachan, France b Oncogenetics, Department of Clinical Oncology, Hôpital Saint-Louis, Unversité Paris7-Paris Diderot, Sorbonne Paris-Cité Paris, France Email: [email protected] 118 Advanced Textbook on Gene Transfer, Gene Therapy and Genetic Pharmacology are also first-choice vectors because they can be manipulated to obtain defective, non-replication-competent viruses in the target cells. Retroviruses are enveloped viruses with positive RNA, two identical RNAs being encapsidated in the viral particle.
eBook - PDF- Roland W Herzog, Sergei Zolotukhin(Authors)
- 2010(Publication Date)
- World Scientific(Publisher)
Chapter 4 Lentiviral Vectors Janka Mátrai, Marinee K. L. Chuah and Thierry VandenDriessche ∗ Lentiviral vectors represent some of the most promising vectors for gene therapy. They have emerged as potent and versatile tools for ex vivo or in vivo gene transfer into dividing and non-dividing cells. Lentiviral vec-tors can be pseudotyped with distinct viral envelopes that influence vector tropism and transduction efficiency. In addition, it is possible to redi-rect vector transduction and generate cell-type specific targetable vectors by incorporating cell-type specific ligands or antibodies into the vector envelope. Lentiviral vectors have been used to deliver genes into various tissues, including brain, retina and liver, by direct in vivo gene deliv-ery. Since they integrate stably into the target cell genome, they are ide-ally suited to deliver genes ex vivo into bona fide stem cells, particularly hematopoietic stem cells (HSCs), allowing for stable transgene expression upon hematopoietic reconstitution. Though there are some safety concerns regarding the risk of insertional mutagenesis, it is possible to minimize this risk by modifying the vector design or by employing integration-deficient lentiviral vectors which, in conjunction with zinc-finger nuclease tech-nology, allow for site-specific gene correction or addition in pre-defined chromosomal loci. Lentiviral gene transfer has provided efficient phe-notypic correction of diseases in mouse models paving the way towards clinical applications. 1. Basic Viral Biology Lentiviruses are enveloped RNA viruses that are surrounded by a lipid bilayer in which the envelope proteins are embedded. The main components ∗ Correspondence: Flanders Institute for Biotechnology,Vesalius Research Center, University of Leuven, Leuven, Belgium. E-mail: [email protected] 53 A Guide to Human Gene Therapy Fig. 4.1 A. Schematic representation of the HIV-1 virus.
eBook - PDF- Moses P. Adoga(Author)
- 2012(Publication Date)
- IntechOpen(Publisher)
5 Viral Vectors in Neurobiology: Therapeutic and Research Applications Renata Coura Centre de Neuroscience Paris Sud – CNPS – Université Paris Sud XI France 1. Introduction 1.1 History and definition of viral vectors Viruses are intracellular parasites with simple DNA or RNA genomes (Figure 1A). Three steps compose virus life cycle: infection of a host cell, replication of its genome within the host cell environment, and formation of new virions (Figure 1B). This process is often but Fig. 1. Virus. (A) Structure. Simplified scheme of virus structure, with a lipid envelope that can be present or not; a protein-composed capsid and the genetic material, that can be DNA or RNA, double or single strand. (B) Life cycle. Example of the course of adeno-associated virus (AAV) productive infection. Scheme showing the eight steps of AAV transduction of host cells: (1) viral binding to a membrane receptor/co-receptor; (2) endocytosis of the virus by the host cell; (3) virus intracellular trafficking through the endosomal compartment; (4) escape of the virus from the endosome; (5) virion uncoating; (6) entry into the nucleus; (7) viral genome conversion from a single-stranded to a double-stranded genome; and (8) integration into the host genome or permanence of an episomal form capable of expressing an encoded gene (from Coura and Nardi, 2008). Molecular Virology 76 not always associated with pathogenic effects against the host organism. Nevertheless, since the mid-1980s, a likely useful role for virus has been envisaged. The idea is to use the unique virus capacity to enter the cell and to replicate their genome to construct vectors, containing the viral envelope and a recombinant genome, so that these vectors could be able to deliver genetic material into cells. Then, recombinant viral vectors are created in which genes essential for viral replication are removed and a gene of interest is inserted in the viral genome (Figure 2).
eBook - PDFViral Diagnostics
Advances and Applications
- Robert S. Marks, Leslie Lobel, Amadou Sall, Robert S. Marks, Leslie Lobel, Amadou Sall(Authors)
- 2014(Publication Date)
- Jenny Stanford Publishing(Publisher)
Because the retrovirus genome is relatively small and well characterized, it is possible to engineer vector-packaging systems Present Lentiviral Production Technologies and Their Limitations 397 that produce vectors that only encode transgenes and do not replicate competent viruses. The most widely used retrovirus vectors to date are based on murine leukemia viruses (MLVs) or HIV-1. A detailed comparison of these three different systems can be found in the review by Baum et al. 4 In this chapter, discussion will be primarily about the development of HIV systems, although many principles can be applied to other retroviral systems. The main advantage of Lentiviruses is their ability to transduce a large range of dividing or nondividing cells, the tropism essentially being driven by the coating envelope pseudotyped. 5,6 Although relatively small, the HIV genome codes for a group of proteins: three structural polyproteins, gag that forms the structure of the virion, env (the surface GP that will primarily interact with the host cell in the first steps of infection), and pol (the viral replication enzymes), as well as several additional genes with regulatory ( tat , rev ) or accessory functions ( vif , vpr , vpu , nef ) flanked by long terminal repeats (LTRs) essential for integration and replication processes. The first generation of the lentiviral vector was made of the nearly intact HIV genome, with the envelope gene disrupted or partially deleted (to prevent the generation of wild-type HIV replicative virion). The surface GP to be incorporated was trans-complemented with a second plasmid coding for the corresponding gene. 7,8 Subsequent developments led to the design of a second and then a third generation.
eBook - PDFViral Vectors
Gene Therapy and Neuroscience Applications
- Michael G. Kaplitt, Arthur D. Loewy(Authors)
- 1995(Publication Date)
- Academic Press(Publisher)
Genetics and Biology of Retroviral Vectors Rajat Bannerii Department of Molecular Biology MemoriaI-Sloan Kettering Cancer Center New York, New York In this chapter, retroviral vectors, based on the Moloney murine leukemia virus, are discussed as a method for delivering genes into target cells. This vector system offers the advantages of highly efficient gene transfer and stable gene expression in the target cell by virtue of the integration of the vector genome into the host chromosomal DNA. Other vector systems including adenovirus vectors, vaccinia virus vectors, and nonviral methods, such as lipo- somes, may allow only transient gene expression (Mulligan, 1993). Adeno- associated virus vectors do have the ability to stabily integrate into the host genome and will be discussed elsewhere (see Samulski, this volume). Helper- free retroviral vectors infect only once and do not spread in vivo, in contrast to other viral vector methods which employ attenuated viruses that may retain the ability to infect other cells. Retroviral vectors have a wide host range, both in terms of species and cell types (Hartley and Rowe, 1976; Rasheed et al., 1976; Luciw and Leung, 1992), but are limited to infecting only dividing cells (Varmus et al., 1977; Fritsch and Temin, 1977; Humphries et al., 1981). Overall, retroviral vectors offer an excellent gene delivery system available for stable gene transfer and expression. Retroviruses are single-stranded RNA viruses encoding a characteristic RNA-dependent DNA polymerase (reverse transcriptase, see Baltimore, 1970; Temin and Mizutani, 1970). They initially were identified as RNA tumor viruses by Peyton Rous, who was working at the Rockefeller Institute on a spontaneous chicken sarcoma (Rous, 1911). Since the discovery of the Rous sarcoma virus (RSV), many tumor causing retroviruses have been found in a variety of vertebrates including reptiles, birds, and mammals.
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