Compare and contrast the replication cycles of…
Compare and contrast the replication cycles of paramyxoviruses (e. g., measles virus), retroviruses (e. g., human immunodeficiency virus or HIV) and alphaherpesviruses (e. g., Varicella-zoster virus or VZV). please refer to their structure +/- , DNA/RNA, Lytic/lysogenic cycles to compare and contrast. I have attached lecture slides to know what points our professors has focused on! Attachment Preview: Lecture_5-0206_Medical_Virology.pdf Download Attachment This is an unformatted preview. Please download the attached document for the original format. BIOL304 Infectious Disease Biology Biology Instructor: Dr. Carsten Sanders BIOL304 Infectious Disease Biology Biology Lecture 5 – 02/06/2014 Medical Virology Part 1 – Virus Structures and Functions • Terminology • General Significance Si • Defining Characteristics Morphologies and Types • Morphologies and Types Source of cover picture: Reece et al. (2010) , Campbell Biology, 9th edition, Pearson Benjamin Cummings, San Francisco (CA), Figure 19.1 BIOL304 Infectious Disease Biology Biology Lecture 5 – 02/06/2014 Medical Virology Part 2 – Growth • Culturing Viruses • Assay and Quantification • Identification Part 3 – Multiplication Mechanisms Multiplication Mechanisms • Bacteriophages • Animal Viruses BIOL304 Infectious Disease Biology Biology Lecture 5 – 02/06/2014 Medical Virology Part 4 – Cytopathogenesis Mechanisms • Transformation of Host Cells • Lytic Infections • Latent and Persistent Infections Part 5 – Classification Classification • The ICTV Classification System • The Baltimore Classification System • Other Classification Schemes BIOL304 Infectious Disease Biology Biology Lecture 5 – 02/06/2014 Medical Virology Part 6 – Protein-based Infectious Particles • General Characteristics • Process of Conversion into Infectious Particle • Disease Mechanisms Pathogenic Features and Symptoms • Pathogenic Features and Symptoms BIOL304 Infectious Disease Biology Biology Homework Assignment Homework Assignment 3 Compare and contrast the replication cycles of paramyxoviruses (e. g., measles virus), retroviruses (e. g., human immunodeficiency virus or HIV) and alphaherperviruses (e. g., Varicella-zoster virus or VZV) (This assignment is due on 02/13/2014) Part 1 – Virus Structures and Functions A. Terminology • Virus: genetic element that cannot replicate Virus genetic element that cannot replicate independently of a living (host) cell • Virology: the study of viruses • Virus particle: extracellular form of a virus; allows virus to exist outside host and facilitates transmission from one host cell to another • Virion: the infectious virus particle; the nucleic acid genome surrounded by a protein coat and, in some cases, other layers of material Part 1 – Virus Structures and Functions B. General Significance • Viruses Viruses ? are small, acellular infectious agents that replicate only inside cellular organisms. They can infect all types of life forms, from animals and plants to bacteria and archaea, and exist naturally within host organisms in complex ecosystems ? the most important roles of viruses are to 1. limit population density of hosts (without their extinction) 2. select for host diversity (by preventing dominance of any di (b one species) • More than 3000 viral species have been described More than 3000 viral species have been described ? about 200 of these are human pathogens Part 1 – Virus Structures and Functions C. Defining Features • Viruses are obligatory intracellular parasites Vi • Contain DNA or RNA (genomes), which can be ? single-stranded or double-stranded or double ? positive-sense or negative-sense (in relation to mRNA, defined as positive-sense RNA, if single-stranded) ? circular, linear and segmented • most viral genomes are very small (between 3 and 50 kilobase pairs or kb) Defining Features Viral Genomes Defining Features • Viruses contain a protein coat • Some are enclosed by an envelope • Some viruses have spikes • Most viruses infect only specific types of cells in one host • Host range is determined by specific host attachment sites and cellular factors • Viruses are submicroscopic in size Viruses are submicroscopic in size ? an electron microscope is needed to see them Defining Features Comparison of Viruses and Cells Part 1 – Virus Functions and Structures C. Morphologies and Types Morphologies and Types Capsid and Capsomere • Capsid: the protein shell that surrounds the genome of a th th th virus particle ? composed of highly repetitive pattern of protein of highly repetitive pattern of protein molecules around the nucleic acid genome • Capsomere: subunit of the capsid ? smallest morphological unit visible with an electron microscope • Nucleocapsid: complete complex of nucleic acid and protein packaged in a virion Capsids and Capsomeres Symmetric Patterns • Capsid (proteins) are generally arranged in one or a limited set of symmetric patterns ? in capsids with rotational symmetry, the subunits pack about the rotational axes to form closed structures ? capsids with helical symmetry tend to form more helical symmetry tend to form more open-ended structures, with subunits added in a spiraling array Symmetry Patterns Rotational Symmetry Rotational Symmetry Polyhedral Viruses Symmetry Patterns Helical Symmetry Helical Symmetry Helical Viruses Symmetry Patterns Summary Morphologies and Types Enveloped Viruses • have membranes, which ? surround nucleocapsids ? are lipid bilayers lipid bilayers with embedded proteins • Envelopes make initial contact with host cell Morphologies and Ty T pes Complex Viruses Complex Viruses • Virions composed of several parts, each with separate shapes and symmetries ? some bacteriophages have icosahedral heads and helical tails Morphologies and Types Comparison of Naked and Enveloped Virus Particles Morphologies and Types Viral Diversity - Animal Viruses Nonenveloped ssDNA Parvovirus Enveloped Nonenveloped Enveloped all ssRNA partially dsDNA Hepadnavirus dsDNA Papovavirus dsDNA ssRNA Picornavirus Rhabdovirus Togavirus Orthomyxovirus dsDNA Poxvirus Adenovirus dsDNA Bunyavirus Coronavirus Arenavirus dsRNA Retrovirus Reovirus 100 nm dsDNA Herpesvirus Iridovirus DNA viruses Paramyxovirus 100 nm RNA viruses Viral Diversity – Animal Viruses Morphologies and Types Enzymes Included in a Virion • Some virions contain enzymes critical to infection ? lysozyme ? nucleic acid polymerases such as RNA-dependent acid polymerases such as RNA DNA polymerase (aka reverse transcriptase) or RNA polymease ? neuramidases, which are enzymes that cleave glycosidic bonds in glycoproteins and glycolipids, and allow liberation of viruses from host Part 2 – Growth A. Culturing Viruses • Viruses only replicate in certain types of cells or whole organisms • Bacterial viruses are typically easiest to grow and are hence often used as model systems ? may be cultured either in batch culture (in liquid) or as be cultured either in batch culture (in liquid) or as isolated plaques on a bacterial lawn (on a plate) • Animal viruses can be cultivated in living animals, in embryogenated eggs, or in tissue or cell cultures • Plant viruses typically are the most difficult experimental models because study often requires growth of a whole plant Culturing Viruses Batch Culture Culturing Viruses Embryonated Egg Culturing Viruses Cell or Tissue Culture Part 2 – Growth B. Assay and Quantification • Titer: number of infectious units per volume of fluid • Plaque assay: analogous to the bacterial colony ? one of the most accurate ways to measure virus infectivity of the most accurate ways to measure virus infectivity • Plaques are clear zones that develop on lawns of host cells ? each plaque results from infection by a single virus plaque results from infection by single virus particle • Animal viruses that do not kill their host cells can be detected by assaying foci, groups of cells infected by the virus Quantification Plaque Assay of Bacteriophages Quantification Plaque Assay of Animal Viruses Quantification Focus Assay of Animal Viruses Part 2 – Growth C. Identification • Distinct patterns of cytopathic effects in culture • Serological tests ? use antibodies to identify virus antigens antibodies to identify virus antigens ? detection of antibodies against viruses in a patient • Nucleic acid-based tests Nucleic acid tests ? restriction fragment length polymorphism/RFLP or polymerase chain reaction/PCR of isolated viral genomes or genome fragments (including reverse transcription for suspected RNA viruses) ? nucleic acid hybridization Identification Cytopathic Effects - Normal Cells versus Infected Cells Part 3 – Multiplication Mechanisms A. Bacteriophages • exhibit two distinct multiplication cycles 1. Lytic or replication cycle ? phage causes lysis and death of host cell causes lysis death of host cell ? generalized transduction: DNA derived from any portion of the host genome is packaged inside the portion of the host genome is packaged inside the mature virion in place of the virus genome Bacteriophages 2. Lysogenic cycle ? virus DNA is incorporated into the host DNA (the phage lysogenizes the host cell and becomes a prophage) ? phage conversion: when lysogenized by a phage, the host cell becomes immune to further infection by the same type of phage ? specialized transduction: DNA from a specific region DNA of the host chromosome is integrated directly into the virus genome, usually replacing some viral genes genome usually replacing some viral genes Bacteriophages Five Steps of the Lytic Cycle • Attachment: Phage attaches by tail fibers to host cell Attachment Phage attaches by tail fibers to host cell • Penetration: Phage lysozyme opens cell wall; tail sheath contracts to force tail core and DNA into cell contracts to force tail core and DNA into cell • Biosynthesis: Production of phage DNA and proteins • Maturation: Assembly of phage particles • Release: Phage lysozyme breaks cell wall Five Steps of the Lytic Cycle Five Steps of the Lytic Cycle Bacteriophage Attachment and Penetration Five Steps of the Lytic Cycle One-Step Viral Growth Curve in Bacterial Hosts during Biosynthesis, Maturation, and Release Five Steps of the Lytic Cycle Time Course of Events in Bacterial Virus Infection Five Steps of the Lytic Cycle Assembly of Complex Bacteriophages Five Steps of the Lytic Cycle Generalized Transduction Bacteriophages Lysogenic Cycle Lysogenic Cycle Induction Generalized Transduction Transduction Phage DNA circularizes and detaches from host DNA A portion of host DNA is exchanged for phage DNA Detached DNA replicates Phage replication is completed. Cell lyses Part 3 – Multiplication Mechanisms B. Animal Viruses Replication Cycle in Six Steps Cycle in Six Steps • Attachment: Viruses attach to cell membrane, binding to specific host cell receptors • Penetration by endocytosis (pinocytosis) or fusion • Uncoating by viral or host enzymes • Biosynthesis: Production of nucleic acids and proteins • Maturation: Nucleic acid and capsid proteins assemble • Release: by budding (enveloped viruses) or rupture Replication Cycle in Six Steps A Prototypical Life Cycle of an Animal Virus Replication Cycle in Six Steps 1 Phage genome inside capsid 2 Capsid Cytoplasmic membrane of host engulfs virus (endocytosis) 3 2 1 3 4 Receptors on cytoplasmic membrane Viral genome Direct penetration 6 Viral glycoproteins 1 2 Envelope 3 Viral glycoproteins remain in cytoplasmic membrane Viral genome Uncoating capsid 5 Endocytosis 4 Receptors on cytoplasmic membrane of host Attachment and and Penetration Viral genome Uncoating capsid Membrane fusion Replication Cycle in Six Steps Uncoating Replication Cycle in Six Steps Production of Viral Nucleic Acids and Proteins • Once a host has been infected, new copies of the viral th genome must be made and virus-specific proteins synthesized in order for the virus to replicate synthesized in order for the virus to replicate • Generation of messenger RNA (mRNA) occurs first yp • Typically, the viral genome serves as a template for viral mRNA • In some RNA viruses, viral RNA itself is the mRNA • In some other cases, essential transcriptional enzymes are contained in the virion Replication Cycle in Six Steps Formation of mRNA by DNA Viruses Replication Cycle in Six Steps DNA Viruses – Protein Synthesis and Genome Replication Replication Cycle in Six Steps Multiplication Multiplication Mechanism of a DNA Virus DNA Virus (Papillomavirus) Replication Cycle in Six Steps Formation of mRNA by RNA Viruses Replication Cycle in Six Steps RNA Viruses – Protein Synthesis and Genome Replication Replication Cycle in Six Steps Multiplication Mechanism of a RNA Virus (Coronavirus) Replication Cycle in Six Steps Release of Enveloped Animal Viruses by Budding by Budding Animal Viruses Comparison of Bacteriophage and Animal Viral Multiplication Part 4 – Cytopathogenesis Mechanisms A. Transformation of Host Cells • The genetic material of tumor-inducing or oncogenic The genetic material of tumor or oncogenic viruses becomes integrated into the host cell DNA • Activated oncogenes transform normal cells into cancerous cells • Virus-transformed cells ? contain virus-specific cell surface antigens ? exhibit (like other cancer cells) increased growth, loss of contact inhibition, and certain chromosomal abnormalities, such as unusual numbers of chromosomes and fragmented chromosomes chromosomes and fragmented chromosomes Viral Transformation of Host Cells Oncogenic DNA and RNA Viruses • Oncogenic DNA viruses ? Adenoviridae ? Herpesviridae ? Poxviridae ? Papovaviridae ? Hepadnaviridae • Oncogenic RNA viruses ? viral RNA is transcribed into DNA which can into DNA, which can integrate into host DNA ? Retroviridae Part 4 – Cytopathogenesis Mechanisms B. Lytic Infections • results when virus replication kills the target cells results when virus replication kills the target cells • some viruses prevent cellular growth and repair by inhibiting the synthesis of cellular macromolecules or by producing degradative enzymes and toxic proteins • virus replication and the accumulation of viral components and progeny within cells can disrupt the function and structure of cells or their organelles • virus infection (or cytolytic immune responses) may induce apoptosis (programmed cell death), which may facilitate the viral release from cells the viral release from cells Lytic Infections • Cell surface expression of viral glycoproteins triggers the fusion of neighboring cells into multinucleated cells called syncytia ? cell-to-cell fusion may occur in the absence of new protein synthesis (fusion from without) or may (f require new protein synthesis (fusion from within) • Syncytia formation allows viruses to spread from cell Syncytia allows viruses to spread from cell to cell and to escape antibody detection ? cells in the state of syncytia are fragile and susceptible to lysis Part 4 – Cytopathogenesis Mechanisms C. Latent and Persistent Infections • usually follow acute infections, but occur in infected cells that are not killed by a virus (nonlytic infections) • Latent infections: viruses remain in asymptomatic host cells for a long period of time until reactivation ? cold sores (herpes simplex virus) or shingles sores (herpes simplex virus) or shingles (varicella-zoster virus) • Persistent (or chronic) infections: disease processes occur Persistent (or chronic) infections disease processes occur gradually over a long period of time and are often fatal ? subacute sclerosing panencephalitis (measles virus) virus) Latent and Persistent Infections Part 4 – Cyt C topathogenesis Mechanisms Tumor cell division Transformation into tumor cell Lysis Cell Virus Death of cell and release of virus Attachment and penetration Virus multiplication Cell fusion Persistent infection Slow release of virus without cell death Latent infection Virus present but not replicating May revert to lytic infection D. Summary Transformation Part 5 – Classification A. The ICTV Classification System • The International Committee on Taxonomy of Viruses The International Committee on Taxonomy of Viruses (ICTV) has devised a classification system, based on several criteria: 1. Genome composition 2. Symmetry of the capsid (protein coat surrounding the viral genome) 3. Envelope 4. Size 5. Host range The ICTV Classification System Nomenclature and Species Definition • A unified taxonomy (universal system) for classifying viruses) has been established ? order (names end in -virales, not assigned for all families) (names end in not assigned for all families) ? family (names end in -viridae) ? subfamily (names end in -virinae) ? genus (names end in -virus) ? species (names end in -virus) ? taxonomic names are used for genus (e. g., lentivirus), while common names are used for species (e. g., human immunodeficiency virus or HIV) Nomenclature and Species Definition • Viral species: a group of viruses sharing the same genetic information and ecological niche (host) ? subspecies, strains and isolates are not distinguished, but are designated by a number (e. g., HIV-1) • over 3,000 species have been described and are organized in 6 orders (Caudovirales, Herpesvirales, Mononegavirales, Nidovirales Picornavirales Nidovirales, Picornavirales and Tymovirales. A seventh Tymovirales seventh order, Ligamenvirales, has been proposed recently) with 108 families (including about 20 subfamilies and 350 genera) Part 5 – Classification B. The Baltimore Classification System • The Nobel Prize-winning biologist David Baltimore divided The Nobel Prize biologist David Baltimore divided viruses into seven groups (Baltimore classification system) ? group I: Double-stranded DNA ? group II: Single-stranded DNA ? group III: Double-stranded RNA ? group IV: (+) single-stranded RNA ? group V: (–) single-stranded RNA ? group VI: RNA retroviruses ? group VII: DNA pararetroviruses • The ICTV classification system is used in conjunction with the The ICTV classification system is used in conjunction with the Baltimore classification system in modern virus classification The Baltimore Classification System The Baltimore Classification System DNA Viruses DNA Viruses Group I – Double-Stranded DNA Viruses DNA Viruses Group II – Single-Stranded DNA Viruses DNA Viruses Group VII – Pararetroviruses DNA Viruses Protein Synthesis and Genome Replication DNA Viruses The Main Groups of Human DNA Viruses The Main Groups of Human DNA Viruses Representative Genera and Associated Diseases Representative Genera and Associated Diseases Herpes Simplex Virus (Simplexvirus) - Herpes Lesions Representative Genera and Associated Diseases Papillomavirus – Warts (Papilloma) The Baltimore Classification System RNA Viruses RNA Viruses Group III – Double-Stranded RNA Viruses RNA Viruses Group IV – (+) Single-Stranded RNA Viruses RNA Viruses Group V – (-) Single-Stranded RNA Viruses RNA Viruses Group VI – Retroviruses RNA Viruses Protein Synthesis and Genome Replication RNA Viruses The Main Groups of Human RNA Viruses The Main Groups of Human RNA Viruses Representative Genera and Associated Diseases Representative Genera and Associated Diseases Morbillivirus (Measles Virus) – Measles Rash and Koplik Spots Part 5 – Classification C. Other Classification Schemes • On the basis of the hosts they infect (host spectrum), viruses On the basis of the hosts they infect spectrum viruses can also be divided into ? bacterial viruses (bacteriophages) ? animal viruses ? plant viruses (etc.) • Moreover, animal viruses may be categorized clinically according to their tropisms (affinities towards specific types of tissues) ? this scheme is limited by the fact that some viruses do not reveal tissue preferences and can infect more than not reveal tissue preferences and can infect more than a single organ or organ system Other Classification Schemes Other Classification Schemes Modes of Transmission • As seen for bacterial, protozoan and helminthic pathogens, viruses (and the infections or diseases they cause) can thirdly be distinguished by their major modes of transmission into be distinguished by their major modes of transmission into 1. foodborne and waterborne 2. airborne 2. airborne 3. acquired via direct contact (including genital contact or sexual transmission) 4. vectorborne (especially arthropodborne = arboviruses) Mode of Transmission Foodborne and Waterborne Infections Mode of Transmission Airborne Infections Infections Mode of Transmission Infections acquired by Direct Contact Infections acquired by Direct Contact Sexually Transmitted Infections Mode of Transmission Vectorborne Infections Part 6 – Protein-based Infectious Particles A. General Characteristics of Prions • Prions are infectious proteins whose extracellular form does not contain nucleic acid • are inherited and transmissible by ingestion, transplant, and surgical instruments • are the etiological agent of spongiform encephalopathies are the etiological agent of spongiform encephalopathies ? in humans: Kuru, Creutzfeldt-Jakob disease, Gerstmann Gerstmann-Straeussler-Scheinker (GSS) syndrome, syndrome, Fatal Familial Insomnia (FFI) ? in animals: Scrapie (sheeps and goats), Bovine Spongiform Encephalopathy (BSE, mad cow disease). General Characteristics of Prions Human and Animal Prion Diseases General Characteristics of Prions • Spongiform Encephalopathies are characterized by ? the appearance of vacuolated neurons including their loss of function ? the lack of an immune response or inflammation Part 4 – Protein-based Infectious Particles B. Process of Conversion into Infectious Particle • Host cell contains a gene (PrnP) encoding a native prion protein form that is found in healthy animals and humans ? PrPC: normal prion protein localized on the cell surface ? PrPSc: scrapie protein, which due to misfolding accumulates in brain cells, forms plaques and results in brain cells forms plaques and results in fusions of neurons and glial cells • Prion misfolding leads to neurological symptoms of disease Prion to neurological symptoms of disease (e. g., resistance to proteases, insolubility, and aggregation) Process of Conversion into Infectious Particle Process of Conversion into Infectious Particle Process of Conversion into Infectious Particle Part 4 – Protein-based Infectious Particles C. Disease Mechanisms • Prion disease occurs by three distinct mechanisms: 1. infectious prion disease: pathogenic form of prion protein is transmitted between animals or humans 2. sporadic prion disease: random misfolding of a normal, healthy prion healthy prion protein in an uninfected individual in an uninfected individual 3. inherited prion disease: mutation in prion gene yields a protein that changes more often into disease protein that changes more often into disease-causing PrPSc form Part 4 – Protein-based Infectious Particles D. Pathogenic Features and Symptoms • Prions have no cytopathologic effect in vitro • Long doubling time of at least 5 days • Long incubation time of up to 30 years • Neurological effects of prion misfolding can be observed as, e. g., vacuolation of neurons (spongiform) and amyolid-like plaques • Symptoms include loss of muscle control, shivering, Symptoms include loss of muscle control shivering tremors, and dementia • Prion accumulation does not lead to antigenicity, inflammation, immune response, or inferon production Pathogenic Features and Symptoms Progression of transmissible Creutzfeldt-Jakob Disease BIOL304 Infectious Disease Biology Biology Check of Understanding • Distinguish virus and virion. • What are capsids and capsomeres? Wh • Compare and contrast the general structures of enveloped and nonenveloped and nonenveloped viruses. • How are viruses cultured, assayed and quantified? • Describe the lytic and lysogenic cycles of bacteriophages. • Define the general multiplication (replication) steps of animal viruses. • Describe the general cytopathogenesis mechanisms of viruses. BIOL304 Infectious Disease Biology Biology Check of Understanding • How are viruses classified? • Define viral species. • Compare and contrast the protein synthesis and genome replication mechanisms of DNA and RNA viruses replication mechanisms of DNA and RNA viruses. • What are the main groups of human DNA and RNA viruses? • What are the general characteristics of protein-based infectious particles (prions) as well as the pathogenic features and symptoms of prion-associated diseases? BIOL304 Infectious Disease Biology Biology Reading Assignment • Engleberg et al., Chapters 31-43, 56 and 71 • Krasner, Chapters 5 and 10 Ch 10 Brief Outline of the Upcoming Lecture Lecture 6 – 02/13/2014 Principles of Infection, Disease, and Epidemiology of Infection Disease and Epidemiology Part 1 – A few reminders from lectures 3-5 Part 2 – Infection and Disease Part 3 – Epidemiology Hide preview Additional Requirements Min Pages: 3 Max Pages: 4 Level of Detail: Show all work Other Requirements: Please use the lecture slides to focus on points and then use outside sources to elaborate them. 3-4 pages; 1.5 spaced Times New Roman 12