10/21/2010. Chapter 13. Ch. 13 Topics. Medical Importance of Viruses

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1 Chapter 13 Viruses, Viroids, and Prions J. Meléndez Lectures prepared by Christine L. Case Ch. 13 Topics Structure Multiplication Cultivation and replication of bacteriophages and animal viruses Non-viral infectious agents Cancer and viral infections Treatment Medical Importance of Viruses Most common cause of acute infections that do not result in hospitalization Most do not cause death but those that do can have very high mortality rates Others can lead to long-term debility 1

2 General Characteristics of Viruses Obligatory intracellular parasites parasites- are inactive outside host cell. They exist in inert particles outside cells as virions Are not cells Ultramicroscopic size: 20nm- 450nm diameter Do not fulfill characteristics of life Basic structure consists of protein shell (capsid) surrounding nucleic acid core Can be DNA or RNA but not both General Characteristics of Viruses Host range: spectrum of hosts that a virus can infect. Different viruses can infect bacteria, fungi, algae, protozoa, etc. However most viruses are limited to only one host and only specific cells or tissues from that host. General Characteristics of Viruses Viral specificity: refers to the specific kind of cells a virus can infects. (tropism)depends on the ability for attachment and the presence of host enzymes and proteins the virus needs for replication. Ex. HIV can infect CD4 cells Hepatitis: can infect liver cells Cytomegalovirus: cells from salivary glands, GI tract, liver, 2

3 Virus Sizes Figure 13.1 Structure 8 Nucleic acid Viruses contain either DNA or RNA Possess only the genes to invade and regulate the metabolic activity of host cells Ex. Hepatitis B (4 genes) and herpesviruses (100 genes) No viral metabolic genes, as the virus uses the host s metabolic resources 3

4 There are two major structures of viruses called the naked nucleocapsid virus and the enveloped virus. Generalized structure of viruses Capsid Protective outer shell that surrounds viral nucleic acid Capsid spikes Composed of capsomer subunits Two types of capsids Helical Polyhedral- (mostly Icosahedral) Virion Structure Nucleic acid DNA or RNA Capsid Capsomeres Envelope Spikes Figure 13.2a 4

5 Function of the capsid /envelope Protect nucleic acid from the host s acid- and protein-digesting enzymes Poliovirus, enteric virus resist acid- and protein- digesting enzymes of GI tract Assist in binding and penetrating host cell Stimulate the host s immune system Morphology of a Polyhedral Virus Figure 13.2 Morphology of an Enveloped Virus Figure

6 Enveloped Viruses Polyhedral virus Figure 13.16b Helical capsid Naked helical virus Ex. Tobacco mosaic virus Nucleocapsid is rigid and tightly wound into a cylindershaped package Enveloped helical virus Ex. Influenza, measles, rabies, ebola Nucleocapsid is more flexible Complex viruses Structure is more intricate than helical and icosahedral viruses Pox virus Several layers of lipoproteins Course surface fibrils Bacteriophage Polyhedral head Helical tail Fibers for attachment 6

7 Taxonomy of Viruses Will not be covered Isolation, Cultivation, and Identification Learning Objectives 13-5 Describe how bacteriophages are cultured Describe how animal viruses are cultured List three techniques used to identify viruses. Primary purposes of viral cultivation To isolate and identify viruses in clinical specimens To prepare viruses for vaccines To do detailed research on viral structure, multiplication cycles, genetics, and effects on host cells Techniques for Cultivating Animal Viruses In vivo methods Laboratory animals : Specially bred strains of white mice, rats, hamsters, guinea pigs, and rabbits Embryonic bird tissues Chicken, duck, and turkey are most common In vitro methods Cell or tissue culture 7

8 Growing Viruses- Bacteriophages Viruses must be grown in living cells Bacteriophages form plaques on a lawn of bacteria Multiplication is similar to animal viruses except for the penetration (inject DNA), release (lyses) and prophage (lysogeny) stages Often make the bacteria they infect more pathogenic for humans Figure 13.6 Growing Viruses- animal viruses Animal viruses may be grown in living animals or in embryonated eggs (inexpensive) (Ex. pox, influenza vaccine) Figure 13.7 Growing Viruses Animal and plant viruses may be grown in cell culture Primary cell lines from tissues (only last a few generations) Continuous cell lines may be maintained indefinitely Figure

9 Virus Identification Cytopathic effects Serological tests Detect antibodies against viruses in a patient Use antibodies to identify viruses in neutralization tests, viral hemagglutination, and Western blot Nucleic acids RFLPs PCR Virus Identification Appearance of normal and infected cell cultures Figure 13.9 Check Your Understanding What is the plaque method? 13-5 Why are continuous cell lines of more practical use than primary cell lines for culturing viruses? 13-6 What tests could you use to identify influenza virus in a patient?

10 Viral Multiplication on bacteriophages Learning Objectives 13-8 Describe the lytic cycle of T-even bacteriophages Describe the lysogenic cycle of bacteriophage lambda. The Lytic Cycle 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 Biosynthesis: Production of phage DNA and proteins Maturation: Assembly of phage particles Release: Phage lysozyme breaks cell wall Lytic Cycle of a T-Even Bacteriophage Figure

11 Lytic Cycle of a T-Even Bacteriophage 4 Figure Results of Multiplication of Bacteriophages Lytic cycle Phage causes lysis and death of host cell Lysogenic cycle Prophage DNA incorporated in host DNA Phage conversion generalized transduction ANIMATION Viral Replication: Virulent Bacteriophages ANIMATION Viral Replication: Temperate Bacteriophages Lysogeny: The Silent Virus Infection Temperate phages- special DNA phages that undergo adsorption and penetration but are not replicated or released immediately (lysogenic phages; ex. lambda) Instead the viral DNA enters an inactive prophage stage Lysogeny: the cell s progeny will also have the temperate phage DNA Lysogenic conversion: when a bacterium acquires a new trait from its temperate phage 11

12 The Lysogenic Cycle Figure Generalized Transduction 2 3 ANIMATION Transduction: Generalized Transduction 4 5 ANIMATION Transduction: Specialized Transduction 6 Figure 8.28 Multiplication of Animal Viruses Attachment: Viruses attach to cell membrane Penetration by endocytosis or fusion Uncoating by viral or host enzymes Biosynthesis: Production of nucleic acid and proteins Maturation: Nucleic acid and capsid proteins assemble Release by budding (enveloped viruses) or rupture 12

13 Attachment, Penetration, Uncoating By pinocytosis Engulfment of virus Figure 13.14a Attachment, Penetration, Uncoating By fusion Cell membrane fuses with viral envelope, envelopes stays outside Figure 13.14b Release: Budding of an Enveloped Virus Figure

14 Comparison of bacterial and animal virus multiplication Viruses and Cancer Learning Objectives Define oncogene and transformed cell Discuss the relationship between viruses and cancer. Cancer Activated oncogenes transform normal cells into cancerous cells Transformed cells have increased growth, loss of contact inhibition, tumor-specific transplant antigens (on cell surface), and T antigens (in nucleus) The genetic material of oncogenic viruses becomes integrated into the host cell's DNA 14

15 Oncogenic Viruses Oncogenic DNA viruses Papovaviridae Papilloma virus (cervical cancer) Hepadnaviridae Hepatitis B virus (liver cancer) Oncogenic RNA viruses Retroviridae Viral RNA is transcribed to DNA, which can integrate into host DNA HTLV-1 HTLV-2 Check Your Understanding What is a provirus? How can an RNA virus cause cancer if it doesn t have DNA to insert into a cell s genome? Provide examples of virus associated with cancers Latent and Persistent Viral Infections Learning Objectives Provide an example of a latent viral infection Differentiate persistent viral infections from latent viral infections. 15

16 Latent and Persistent Viral Infections Figure Latent Viral Infections Virus remains in asymptomatic host cell for long periods Cold sores, shingles Figure Persistent Viral Infections Disease processes occurs over a long period; generally is fatal Subacute sclerosing panencephalitis (measles virus) HIV AIDS Cervical cancer (papilloma virus) Figure

17 Check Your Understanding Is shingles a persistent or latent infection? 13-13, Prions, Viroids, and Plant Viruses Learning Objectives Discuss how a protein can be infectious Differentiate virus, viroid, and prion. Prions Protein particle with no nucleic acid, no envelope, no capsid Proteinaceous Infectious particle Cause nine neurological diseases (spongiform encephalopathies) Creutzfeldt-Jakob (CJD) in humans Bovine spongiform encephalopathy (Mad cow disease) Inherited and transmissible by ingestion, transplant, and surgical instruments Spongiform encephalopathies: Sheep scrapie, Creutzfeldt- Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, mad cow disease 17

18 Plant Viruses and Viroids Plant viruses: Enter through wounds or via insects Viroids: Infectious RNA, no capsid; e.g. Tomatoes, potatoes, cucumbers, Plant pathogens 1/10 th the size of normal viruses Figure Check Your Understanding Contrast viroids and prions, and name a disease it causes , How are viruses, viroids and prions different? Treatment of Animal Viral Infections Because they are not bacteria, antibiotics are ineffective Antiviral drugs block virus replication by targeting one of the steps in the viral life cycle Interferon shows potential for treating and preventing viral infections Vaccines stimulate immunity 54 18

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