1. Ch 13
Viruses and Prions

2. Student 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.

3. Foundations 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

5. General Characteristics of Viruses
Obligatory intracellular parasites
Filterable
Virus = Latin for poison
Contain DNA or RNA
Contain a protein coat = capsid made up of capsomeres. Various shapes
Some are enclosed by an envelope (naked vs. enveloped)
Some viruses have spikes (COH/protein)
Most viruses are tissue specific
Host range is determined by specific host attachment sites and cellular factors

6. Virus Shapes and Sizes
Fig 13.1

7. Polyhedral

8. Electron micrograph of Aeromonas virus 31, an unassigned virus in the family Myoviridae
photograph by Dr Hans Ackermann.

9. Morphology of an enveloped helical virus
Fig 13.3

10. Host Range and Specificity
Virus / host cell interaction usually very specific (narrow host range) – due to?
Tissue tropism
Doc Kaiser's Microbiology Home Page Copyright © Gary E. Kaiser All Rights Reserved Updated: March 15, 2001

11. Taxonomy of Viruses No evidence for common viral ancestor.
Classification based on type of NA, strategy for replication, and morphology.
Family names end in –viridae
Genus 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.

12. Taxonomy of Viruses Retroviridae Herpesviridae Lentivirus Herpesvirus
Human herpes virus HHV-1, HHV-2, HHV-3
Retroviridae
Lentivirus
Human immunodeficiency virus HIV-1, HIV-2

13. Isolation, Cultivation, and Identification of Viruses
Fig 13.6
Viruses must be grown in living cells
Bacteriophages form plaques on a lawn of bacteria
Animal viruses may be grown in cell culture, embryonated eggs, or living animals
Fig 13.8

14. 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
Novel methods such as Biophotonics

15. Viral Replication
Obligate intracellular parasites using host cell machinery
Very limited number of genes encode proteins for
Capsid formation
Viral nucleic acid replication
Movement of virus into and out of cell
Kill or live in harmony within the host cell – Outside the cell, viruses are inert

16. Bacteriophage: The Lytic Cycle
Attachment to cell surface receptors (chance encounter – no active movement)
Penetration – only genome enters
Biosynthesis – Production of phage DNA and proteins
Maturation – assembly to form intact phage
Release due to phage induced lysozyme production
See Fig 13.11

17. Lytic Cycle of a T-Even Bacteriophage1 2 3
Fig 13.11

18. Lytic Cycle of a T-Even Bacteriophage4
Fig 13.11

19. Results of Multiplication of Bacteriophages
Lytic cycle
Lytic or virulent phage
Phage causes lysis and death of host cell
Lysogenic cycle
Lysogenic or temperate phage
Phage DNA incorporated in host DNA  Prophage
Phage conversion
Specialized transduction
ANIMATION Viral Replication: Virulent Bacteriophages
ANIMATION Viral Replication: Temperate Bacteriophages

20. Lytic and Lysogenic Cycles
Fig 13.12

21. Some animal viruses exit the host cells via budding.
HSV envelopment and release
Compare to Fig

22. Multiplication of DNA Viruses
Foundation Fig 13.15
ANIMATION Viral Replication: Animal Viruses

23. Multiplication of RNA Viruses
Fig 13.17

24. Multiplication of a Retrovirus
Fig 13.19

25. Cancer Cancer  uncontrolled mitotic divisions
Benign vs. malignant tumors
Oncology
3 important characteristics of cancer cells:
Rapid cell division
Loss of anchoring junctions and contact inhibition  metastasis
Dedifferentiation of cells

26. Viruses and Cancer
The genetic material of oncogenic viruses becomes integrated into the host cell’s DNA (provirus).
Conversion of proto-oncogenes to oncogenes
Activated oncogenes transform normal cells into cancerous cells
Transformed cells have increased growth, loss of contact inhibition, tumor-specific transplant antigens, and T antigens
Oncogenic Viruses are responsible for 10 % of human cancers

27. Oncogenic DNA Viruses and RNA Viruses
Hepatitis C virus (HCV)  liver cancer
human T-cell leukemia virus (HTLV-1)
Papilloma virus (HPV)  cervical cancer
Epstein-Barr virus (EBV)  Burkitt’s lymphoma
HV8  Kaposi’s sarcoma
Hepatitis B virus (HBV)  liver cancer
HPV 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.

28. Latent and Persistent Viral Infections
Latent: Virus remains in asymptomatic host cell for long periods
Persistent: Disease processes occurs over a long period; generally is fatal
Fig 13.21

29. Prions
Small proteinaceous infectious particles (very resistant to inactivation)
Inherited and transmissible by ingestion, transplant, and surgical instruments
Causes spongiform encephalopathies:
Sheep scrapie,
Creutzfeldt-Jakob disease,
Gerstmann-Sträussler-Scheinker syndrome,
fatal familial insomnia,
mad cow disease
PrPC: Normal cellular prion protein, on cell surface. Involved in cell death.
PrPSc: Scrapie protein; accumulates in brain cells, forming plaques.

30. Spongiform Encephalopaties
Caused by altered protein:
Mutation in normal PrPc gene (sporadic CJD), or
contact with the abnormal PrPSc protein
The 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, elk
BSE (bovine spongiform encephalopathy): cows
Kuru 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: Diseases
ANIMATION Prion: Characteristics
ANIMATION Prion: Overview
The End