2Student Learning Outcomes Differentiate a virus from a bacterium. Explain the difference between enveloped and nonenveloped viruses. Define viral species. Describe how bacteriophages and animal viruses are cultured. Compare and contrast the lytic and lysogenic cycles of bacteriophages. Define oncogene and transformed cell. Discuss the relationship between viruses and cancer. Explain latent viral infections and give an example. Discuss how a proteins can be infectious.
3Foundations of Virology Non-living agents that infect all life forms (phages vs. animal viruses)Viral cultivation differs from bacterial cultivation 1,500 known viruses (estimates: 400,000 exist)Advent of EM allowed for visualization of viruses
5General Characteristics of Viruses Obligatory intracellular parasitesFilterableVirus = Latin for poisonContain DNA or RNAContain a protein coat = capsid made up of capsomeres. Various shapesSome are enclosed by an envelope (naked vs. enveloped)Some viruses have spikes (COH/protein)Most viruses are tissue specificHost range is determined by specific host attachment sites and cellular factors
11Taxonomy of Viruses No evidence for common viral ancestor. Classification based on type of NA, strategy for replication, and morphology.Family names end in –viridaeGenus and species names end in -virus.Viral species: A group of viruses sharing the same genetic information and ecological niche (host). Common names are used for species.Subspecies are designated by a number.
12Taxonomy of Viruses Retroviridae Herpesviridae Lentivirus Herpesvirus Human herpes virus HHV-1, HHV-2, HHV-3RetroviridaeLentivirusHuman immunodeficiency virus HIV-1, HIV-2
13Isolation, Cultivation, and Identification of Viruses Fig 13.6Viruses must be grown in living cellsBacteriophages form plaques on a lawn of bacteriaAnimal viruses may be grown in cell culture, embryonated eggs, or living animalsFig 13.8
14Virus Identification Cytopathic effects Serological tests Detect antibodies against viruses in a patientUse antibodies to identify viruses in neutralization tests, viral hemagglutination, and Western blotNucleic acidsRFLPsPCRNovel methods such as Biophotonics
15Viral ReplicationObligate intracellular parasites using host cell machineryVery limited number of genes encode proteins forCapsid formationViral nucleic acid replicationMovement of virus into and out of cellKill or live in harmony within the host cell – Outside the cell, viruses are inert
16Bacteriophage: The Lytic Cycle Attachment to cell surface receptors (chance encounter – no active movement)Penetration – only genome entersBiosynthesis – Production of phage DNA and proteinsMaturation – assembly to form intact phageRelease due to phage induced lysozyme productionSee Fig 13.11
17Lytic Cycle of a T-Even Bacteriophage 123Fig 13.11
18Lytic Cycle of a T-Even Bacteriophage 4Fig 13.11
19Results of Multiplication of Bacteriophages Lytic cycleLytic or virulent phagePhage causes lysis and death of host cellLysogenic cycleLysogenic or temperate phagePhage DNA incorporated in host DNA ProphagePhage conversionSpecialized transductionANIMATION Viral Replication: Virulent BacteriophagesANIMATION Viral Replication: Temperate Bacteriophages
25Cancer Cancer uncontrolled mitotic divisions Benign vs. malignant tumorsOncology3 important characteristics of cancer cells:Rapid cell divisionLoss of anchoring junctions and contact inhibition metastasisDedifferentiation of cells
26Viruses and CancerThe genetic material of oncogenic viruses becomes integrated into the host cell’s DNA (provirus).Conversion of proto-oncogenes to oncogenesActivated oncogenes transform normal cells into cancerous cellsTransformed cells have increased growth, loss of contact inhibition, tumor-specific transplant antigens, and T antigensOncogenic Viruses are responsible for 10 % of human cancers
27Oncogenic DNA Viruses and RNA Viruses Hepatitis C virus (HCV) liver cancerhuman T-cell leukemia virus (HTLV-1)Papilloma virus (HPV) cervical cancerEpstein-Barr virus (EBV) Burkitt’s lymphomaHV8 Kaposi’s sarcomaHepatitis B virus (HBV) liver cancerHPV includes more than 100 different strains or types. More than 30 of these viruses are sexually transmitted, and they can infect the genital area of men and women including the skin of the penis, vulva (area outside the vagina), or anus, and the linings of the vagina, cervix, or rectum. Most people who become infected with HPV will not have any symptoms and will clear the infection on their own. In June 2006, the Advisory Committee on Immunization Practices (ACIP) voted to recommend the first vaccine developed to prevent cervical cancer and other diseases in females caused by certain types of genital human papillomavirus (HPV). The vaccine, Gardasil®, protects against four HPV types, which together cause 70% of cervical cancers and 90% of genital warts.The Food and Drug Administration (FDA) recently licensed this vaccine for use in girls/women, ages 9-26 years. The vaccine is given through a series of three shots over a six-month period.A sarcoma is a cancer that develops in connective tissues such as cartilage, bone, fat, muscle, blood vessels, or fibrous tissues (related to tendons or ligaments). Kaposi sarcoma (KS) was named for Dr. Moritz Kaposi who first described it in 1872.
28Latent and Persistent Viral Infections Latent: Virus remains in asymptomatic host cell for long periodsPersistent: Disease processes occurs over a long period; generally is fatalFig 13.21
29PrionsSmall proteinaceous infectious particles (very resistant to inactivation)Inherited and transmissible by ingestion, transplant, and surgical instrumentsCauses spongiform encephalopathies:Sheep scrapie,Creutzfeldt-Jakob disease,Gerstmann-Sträussler-Scheinker syndrome,fatal familial insomnia,mad cow diseasePrPC: Normal cellular prion protein, on cell surface. Involved in cell death.PrPSc: Scrapie protein; accumulates in brain cells, forming plaques.
30Spongiform Encephalopaties Caused by altered protein:Mutation in normal PrPc gene (sporadic CJD), orcontact with the abnormal PrPSc proteinThe word prion is a compound word derived from the initial letters of the words proteinaceous and infectious, with -on added by analogy to the word virion.[The incidence of sporadic CJD is about 1 per million per year.CWD (chronic wasting disease): muledeer, elkBSE (bovine spongiform encephalopathy): cowsKuru is the condition which first brought prion diseases to prominence in the 1950s. Found in geographically isolated tribes in the Fore highlands of New Guinea. Established that ingesting brain tissue of dead relatives for religious reasons was likely to be the route of transmission. They ground up the brain into a pale grey soup, heated it and ate it. Clinically, the disease resembles CJD. Other tribes in the vicinity with same religious habit did not develop the disease. It is speculated that at some point in the past a tribe member developed CJD, and as brain tissue is highly infectious this allowed the disease to spread. Afflicted tribes were encouraged not to ingest brain tissue and the incidence of disease rapidly declined and is now almost unknown.Prions are proteins that are found in the brains of both normal and afflicted individuals. Prion proteins are found in two forms, the wild type form (PrPc) and the mutant form (PrPsc). Even after much research the actual function of these proteins still remains a mystery. Yet, prions (proteinaceous infectious particles), have been linked to many diseases. The origins of these diseases were previously an enigma; the sources could be linked to neither a bacterial agent nor a viral agent. Via some creative thinking by a man named Stanley B. Prusiner, the prion idea was hypothesized. Prion diseases:ANIMATION Prion: DiseasesANIMATION Prion: CharacteristicsANIMATION Prion: OverviewThe End