1. Virions, Prions, and Viroids: Infectious Agents of Animals and Plants Topics Structure Classification Methods of study Viral infections Viral tumors Human tumors Viral host range Prions

2. Structure Analogous to bacteriophages Capsid (protein coat) made up of capsomeres Naked vs. enveloped viruses Attachment proteins or spikes in enveloped viruses Distinct from bacteriophages Segmented viruses (contain more than one RNA molecule) Plant viruses do not enter via receptor attachment Shapes: Isometric Helical Pleomorphic

3. Classification Taxonomy in constant flux Most common taxonomic criteria for animal viruses: 1.Genome structure (DNA or RNA, ss vs. ds, segmented or not) 2.Virus particle structure (isometric, helical, pleomorphic) 3.Presence or absence of viral envelope Viruses infecting vertebrates are divided into 14 RNA families and 7 DNA families (Ending: -viridae)

4. Coronavirus Classification: –Coronaviridae (Family) –Coronavirus (Genus) –Common cold virus (Species) (together with rhinoviruses) Structure: –non-seg., lin., ssRNA, helical, env.

5. Herpesvirus Classification: –Herpesviridae (Family) –Herpesvirus (Genus) –Herpes simplex type 1 / type 2 (Species) Structure: –non-seg., lin., dsDNA, helical, env. http://darwin.bio.uci.edu/~faculty/wagner/movieindex.html

6. Cells Infected with a Herpes Virus

7. Groupings Based on Routes of Transmission Not a taxonomic grouping – more than one family may be included in one transmission grouping

8. Methods of Study Much more expensive and difficult to study animal viruses than bacteriophages Cultivation in host cells –Living animal –Embryonated chicken eggs –Cell or tissue culture (= in vitro)

9. Methods of Study cont: Quantitation Plaque assay (useful for infective and lytic viruses) Virion counting with EM Quantal assay (ID 50 or LD 50 ) Hemagglutination (e.g.influenza virus)

10. Acute Viral Infections Productive infection of relative short duration Naked viruses usually cause cell lysis, while enveloped viruses do not Symptoms due to localized or widespread tissue damage Host defense mechanisms gradually eliminate virus Examples Examples of acute infections Time course

11. Mumps, Measles, Influenza, and Poliomyelitis

12. Time Course of Acute Viral Infection

13. HEV

14. Reproductive Cycle 1.Attachment 2.Entry 3.Uncoating 4.Replication of NA and protein 5.Maturation of viral particles 6.Cell lysis 7.Spreading and shedding 8.Transmission to next host

15. Transcription Strategy

16. Mechanisms of Release 1.Cytopathic effect: Unlike virulent phages most animal viruses do not encode for cell lytic enzymes. Instead degenerative changes associated with the virus lead to cell death. 2.Budding: from plasma membrane (most common) or from Golgi apparatus. May or may not kill cell. Enveloped viruses

17. Persistent Viral Infections Virus continually present in body. Released by budding. May or may not cause disease Carrier able to spread disease Four categories (if more than one applies = complex infections): 1.Late complications from acute infections 2.Latent infections 3.Chronic infections 4.Slow infections

18. Late Complications from Acute Infections 1.Subactue sclerosing panencephalitis (SSPE) - years following measles in 1 in 300,000. Virus persistent in brain tissue with decreased transcription of viral genome. Lack of envelope protein production prevents immune response to eliminate infected cells. High Ab, low CMI. Exact mechanism unknown. 2.Progressive (pan)encephalitis following rubella

19. Latent Infections Acute infection  symptomless period  reactivation of disease Symptoms of reactivation may differ from original disease No measurable viral particles during symptomless period Examples: HSV-1 and HSV-2; varicella

20. Chickenpox - Varicella Blister-like rash on surface of skin and mucous membranes. Blisters usually appear first on trunk and face, then spread to almost everywhere else.

21. Shingles or Herpes Zoster About 20 % of those people who have had chicken pox will get zoster at some time during their lives. Most people will get zoster only once.

22. “ Shingles ” comes from latin cingulum, which means girdle or belt. It occurs in an area of the skin that is supplied by the sensory fibers of a single nerve- dermatome. Rash appears as well-defined band on one side of body, or on one side of face, arms or legs.

23. Chronic Infections Virus can be demonstrated at all times Disease may or may not be present for extended time periods or show up late (carriers!)

24. Slow Infections Gradual increase of infectious agent over long time period – often no apparent symptoms for long time (=preclinical phase) Usually slowly progressive lethal diseases Examples –AIDS –Lentivirus –prions

25. HIV: Example of Complex Infection Retrovirus – ssRNA, envelope RNA  DNA (with the help of reverse transcriptase)  permanent integration into host genome (=provirus) Polyprotein is cleaved into individual proteins with viral protease  assembly of virions  budding

26. Viral Tumors (Neoplasms) Benign Malignant  cancer, metastasizes Proto-oncogenes and oncogenes are regulatory genes Properties of normal and transformed cells Only about 15% of human tumors are due to viruses Examples of human tumors: –Kaposi’s sarcoma (herpes virus) –Squamous cell carcinomas (HPV) –Hepatocellular carcinoma (HBV and HCV)

27. Kaposi’s Sarcoma Purplish lesions of a skin cancer not usually seen in young men

28. Viral Host Range Mostly species – and even cell type – specific Exception: Zoonotic viruses are transmissible from animals (arthropods, vertebrates) to man (zoonosis) –Arboviruses (West Nile virus), rabies etc. Modification of host range due to –Phenotypic mixing –Genetic reassortment

29. Genetic Reassortent In segmented viruses Simultaneous infection of one cell with 2 different types of viruses leads to exchange of genetic information Creation of major new influenza strains  resulting in pandemics Antigenic shift vs. antigenic drift

30. Other Infectious Agents: Prions Small proteinaceous infectious particles (resist inactivation by procedures that modify nucleic acids) Prion diseases are often called spongiform encephalopathies because of the post mortem appearance of the brain with large vacuoles in the cortex and cerebellum Human prion diseases –CJD: Creutzfeld-Jacob Disease –BSE: Mad cow disease (BSE) –GSS: Gerstmann-Straussler-Scheinker syndrome –Kuru