Online Counseling Resource YCMOU ELearning Drive… School of Architecture, Science and Technology Yashwantrao Chavan Maharashtra Open University, Nashik – 422222, India SBT/SBI/SGS011-CP2-02 Introduction Programmes and Courses SEP –SBT011-CP2-U2 SEP –SBT011 -CP2–U2 SEP – SGS011-CP2-U2 School of Science and Technology, Online Counseling Resource… Credits Academic Inputs by Sonali Alkari Faculty YCMOU Nagpur Centre, Faculty LAD college P.G. D of Biotechnology Research officer Ankur Seeds Pvt Ltd [email protected] [email protected] School of Science and Technology, Online Counseling Resource… How to Use This Resource Counselor at each study center should use this presentation to deliver lecture of 40-60 minutes during Face-To-Face counseling. Discussion about students difficulties or tutorial with assignments should follow the lecture for about 40-60 minutes. Handouts (with 6 slides on each A4 size page) of this presentation should be provided to each student. Each student should discuss on the discussion forum all the terms which could not be understood. This will improve his writing skills and enhance knowledge level about topics, which shall be immensely useful for end exam. Appear several times, for all the Self-Tests, available for this course. Student can use handouts for last minutes preparation just before end exam. © 2007, YCMOU. All Rights Reserved. 4 School of Science and Technology, Online Counseling Resource… Learning Objectives After studying this module, you should be able to: Describe viruses replication Discuss different phases in virus replication Explain HIV , Transmission, genome and structure, variability etc. © 2007, YCMOU. All Rights Reserved. 5 School of Science and Technology, Online Counseling Resource… Virus Replication Viruses do not contain the enzymes and metabolic precursors necessary for selfreplication. They have to get these from the host cells that they infect. Viral replication, therefore, is a process of separate synthesis of viral components and assembly of these into new virus particles. Replication begins when a virus enters the cell . The virus coat is removed by cellular enzymes, and the virus RNA or DNA comes into contact with ribosomes (cell organs that synthesize proteins) inside the cell. School of Science and Technology, Online Counseling Resource… Virus Replication:1 There the virus RNA or DNA directs the synthesis of proteins specified by the viral nucleic acid. The nucleic acid replicates itself, and the protein subunits constituting the viral coat are synthesized. Thereafter, the two components are assembled into a new virus. One infecting virus can give rise to thousands of progeny viruses. Some viruses are released by destruction of the infected cell. School of Science and Technology, Online Counseling Resource… Virus Replication:2 Others are released by budding through cell membranes and do not kill the cell. In some instances, infections are “silent”— that is, viruses may replicate within the cell but cause no obvious cell damage . The RNA-containing viruses are unique among replicative systems in that the RNA can replicate itself independently of DNA. In some cases, the RNA can function as messenger RNA, indirectly replicating itself using the cell's ribosomal and metabolic precursor systems. School of Science and Technology, Online Counseling Resource… Virus Replication:3 In other cases, RNA viruses carry within the coat an RNA-dependent enzyme that directs the synthesis of virus RNA. Some RNA viruses, which have come to be known as retroviruses, may produce an enzyme that can synthesize DNA from the RNA molecule. The DNA thus formed then acts as the viral genetic material. Bacterial viruses and animal viruses differ somewhat in their interaction with the cell surface during infection. School of Science and Technology, Online Counseling Resource… Virus Replication:4 The “T even” bacteriophage that infects the bacterium Escherichia coli, for instance, first attaches to the surface and injects its DNA directly into the bacterium. No absorption and uncoating take place. The basic events of virus replication, however, are the same after the nucleic acid enters the cell. School of Science and Technology, Online Counseling Resource… Steps in Viral Replication The following steps replication;- take place during I. Adsorption II. Penetration III.Uncoating IV.Viral genome replication V. Maturation VI.Release viral School of Science and Technology, Online Counseling Resource… 1. Adsorption The first step in infection of a cell is attachment to the cell surface. Attachment is via ionic interactions which are temperature-independent. The viral attachment protein recognizes specific receptors, which may be protein, carbohydrate or lipid, on the outside of the cell. Cells without the appropriate receptors are not susceptible to the virus. School of Science and Technology, Online Counseling Resource… 2. Penetration Penetration rapidly follows adsorption, and the virus can no longer be recovered from the intact cell. The most common mechanism is receptor mediated endocytosis, the process by which many hormones and toxins enter cells. The virion is endocytosed within a cytoplasmic vacuole. and contained School of Science and Technology, Online Counseling Resource… 2. Penetration Enveloped viruses Some enveloped viruses require an acid pH for fusion to occur and are unable to fuse directly with the plasma membrane. These viruses are taken up by invagination of the membrane into endosomes. As the endosomes become acidified, the latent fusion activity of the virus proteins becomes activated by the fall in pH and the virion membrane fuses with the endosome membrane. This results in delivery of the internal components of the virus to the cytoplasm of the cell School of Science and Technology, Online Counseling Resource… Virus Replication School of Science and Technology, Online Counseling Resource… 2. Penetration Non-enveloped viruses Non-enveloped viruses may cross the plasma membrane directly or may be taken up into endosomes. They then cross (or destroy) the endosomal membrane. School of Science and Technology, Online Counseling Resource… 3. Uncoating Nucleic acid has to be sufficiently uncoated so that virus replication can begin at this stage. A key step in uncoating is the acidification of the content of the endosome to a pH of about 5, owing to the activity of a proton pump present in the membrane. The low pH causes rearrangement of coat components, which then expose normally hidden hydrophobic sites. They bind to the lipid bilayer of the membrane, causing the extrusion of the viral core into the cytosol. For influenza virus, the acid-sensitive component is the core HA2 unit of the haemagglutinin, for adenoviruses, it is the penton base. School of Science and Technology, Online Counseling Resource… 4. Synthesis of Viral Nucleic Acid and Protein Many strategies are used. Virulent viruses, either DNA and RNA, shut off cellular protein synthesis and disaggregate cellular polyribosomes, favouring a shift to viral synthesis. The mechanism of protein synthesis shut-off varies even within the same viral family. Poliovirus, using a viral protease, causes cleavage of a 200 Kd cap-binding protein, which is required for initiation of translation of capped cellular messengers. In contrast to virulent viruses, moderate viruses e.g. polyomaviruses may stimulate the synthesis of host DNA, mRNA, and protein. School of Science and Technology, Online Counseling Resource… 5. Assembly/Maturation New virus particles are assembled. There may be a maturation step that follows the initial assembly process. School of Science and Technology, Online Counseling Resource… 6. Release Virus may be released due to cell lysis, or, if enveloped, may bud from the cell. Budding viruses (figures 3 and 4) do not necessarily kill the cell. T hus, some budding viruses may be able to set up persistent infections. Not all released viral particles are infectious. The ratio of non-infectious to infectious particles varies with the virus and the growth conditions. School of Science and Technology, Online Counseling Resource… Virus Replication School of Science and Technology, Online Counseling Resource… Human Immunodeficiency Virus (HIV)-1 (HIV) is a retrovirus Scanning electron micrograph of HIV-1 (in green) budding from cultured lymphocyte. Multiple round bumps on cell surface represent sites of assembly and budding of virions that can lead to acquired immunodeficiency syndrome (AIDS). AIDS IS a condition in humans in which the immune system begins to fail, leading to lifethreatening opportunistic infections. School of Science and Technology, Online Counseling Resource… HIV:2 HIV is a member of the genus Lentivirus, part of the family of Retroviridae. Lentiviruses have many common morphologies and biological properties. Many species are infected by lentiviruses, which are characteristically responsible for longduration illnesses with a long incubation period. Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon entry of the target cell, the viral RNA genome is converted to double-stranded DNA by a virally encoded reverse transcriptase that is present in the virus particle. School of Science and Technology, Online Counseling Resource… HIV:3 This viral DNA is then integrated into the cellular DNA by a virally encoded integrase, along with host cellular co-factors, so that the genome can be transcribed. Once the virus has infected the cell, two pathways are possible: either the virus becomes latent and the infected cell continues to function, or the virus becomes active and replicates, and a large number of virus particles are liberated that can then infect other cells. School of Science and Technology, Online Counseling Resource… Routes of HIV Transmission The four major routes of transmission are unprotected sexual intercourse , contaminated needles, breast milk, and transmission from an infected mother to her baby at birth. Screening of blood products for HIV has largely eliminated transmission through blood transfusions or infected blood products in the developed world. HIV primarily infects vital cells in the human immune system such as helper T cells (specifically CD4+ T cells), macrophages and dendritic cells. School of Science and Technology, Online Counseling Resource… HIV Infection HIV infection leads to low levels of CD4+ T cells through three main mechanisms: Firstly, direct viral killing of infected cells; Secondly, increased rates of apoptosis in infected cells; and Thirdly, killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that recognize infected cells. When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections. School of Science and Technology, Online Counseling Resource… Structure and Genome:1 HIV is different in structure from other retroviruses. It is about 120 nm in diameter (120 billionths of a meter; around 60 times smaller than a red blood cell, yet large for being a virus) and roughly spherical. It is composed of two copies of positive single-stranded RNA that codes for the virus's nine genes enclosed by a conical capsid composed of 2,000 copies of the viral protein p24. The single-stranded RNA is tightly bound to nucleocapsid proteins, p7 and enzymes needed for the development of the virion such as reverse transcriptase, proteases, ribonuclease and integrase. A matrix composed of the viral protein p17 surrounds the capsid ensuring the integrity of the virion particle. School of Science and Technology, Online Counseling Resource… Structure and Genome:2 School of Science and Technology, Online Counseling Resource… HIV Replication Cycle School of Science and Technology, Online Counseling Resource… Genetic Variability HIV differs from many viruses in that it has very high genetic variability. This diversity is a result of its fast replication cycle, with the generation of 109 to 1010 virions every day, coupled with a high mutation rate of approximately 3 x 10-5 per nucleotide base per cycle of replication and recombinogenic properties of reverse transcriptase. School of Science and Technology, Online Counseling Resource… What You Learn… You have learnt : Viral replication, therefore, is a process of separate synthesis of viral components and assembly of these into new virus particles The various steps of viral replication are Adsorption, Penetration,Uncoating Viral genome replication, Maturation and Release . HIV is a retrovirus that can lead to acquired immunodeficiency syndrome (AIDS) HIV differs from many viruses in that it has very high genetic variability. School of Science and Technology, Online Counseling Resource… Critical Thinking Questions 1. Describe is in detail the process of virus replication? 2. What is virus? Human immunodeficiency 3. Write a short note on HIV transmission and infection. © 2007, YCMOU. All Rights Reserved. 32 School of Science and Technology, Online Counseling Resource… Hints For Critical Thinking Question 1. process of separate synthesis of viral components, various steps in virus replication. 2. Details of HIV, infection, transmission and ultimate effect. 3. four major routes of transmission and three main mechanisms of HIV © 2007, YCMOU. All Rights Reserved. 33 School of Science and Technology, Online Counseling Resource… Study Tips Book1 Title:The Living World Author: George Johnson Book2 Title: ABC Of Biology Publisher: Holy Faith Book3 Title: Biological Science Author: Taylor, Green & Stout School of Science and Technology, Online Counseling Resource… Study Tips www.en.wikipedia.org Microsoft Encarta Encyclopedia http://en.wikipedia.org/wiki/ Wikipedia the free encyclopedia School of Science and Technology, Online Counseling Resource… End of the Presentation Thank You !
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