1. Viruses At the Threshold of Life 6

2. The Nature of Viruses Not really alive Not really completely inert Existence somewhere between living objects and chemical compounds

3. The Discovery and Structure of Viruses The development of virology –1892 Dmitri Iwanoski Tobacco mosaic virus (TMV) Bacteria-free filtrate still infectious 1898 Martinus Beijerinck supported these data –1930s Wendell Stanley Crystals of TMV indicated chemical molecule Body responses indicated infectious microbes The debate continued… –1933 Ernst Ruska Invention of electron microscope Finally allowed visualization of viruses Figure 6.1a: The Russian pathologist Dmitri Iwanowski © National Library of Medicine

4. The Discovery and Structure of Viruses The structure of viruses –Size As small as 27 nm (0.027  M); poliovirus At least as large as 250 nm (0.25  M); smallpox At least 500 could fit inside single bacterium!

5. The Discovery and Structure of Viruses The structure of viruses –Symmetry Helix Icosahedron Complex

6. The Discovery and Structure of Viruses

7. The components of viruses –Minimum of nucleic acid and protein = naked –Some have an outer envelope –Nucleic acid Called the “Genome” RNA or DNA, not both Segmented or non-segmented Circular or linear Single-stranded or double-stranded –Protein Capsid Capsomeres –Nucelocapsid = genome + capsid The Discovery and Structure of Viruses Fig. 6.4a: naked Icosahedral virus Fig. 6.4b: A naked helical virus

8. The components of viruses –Envelope Lipids Spikes –No cytoplasm –No metabolism –No increase or decrease in size The Discovery and Structure of Viruses Fig. 6.4 Icosahedral and helical viruses

9. Figure 6.COinsert: A TEM of the ultra structural details of a number of influenza virus particles, or “virions” Courtesy of Dr. F.A. Murphy/CDC

10. Viral Replication: Lytic Cycle

11. Viral Replication Viral replication and disease –Destruction of healthy cells –EXAMPLES Viral hepatitis –Destruction of liver cells by infection –Loss of liver function AIDS –Destruction of immune cells –Loss of immune control over other infectious agents Rabies –Destruction of nerves –Loss of control by nervous system

12. Viral Replication Defense against viruses –Immune system Antibodies: protein molecules made by B cells in the immune system, in response to the presence of a virus. T cells: attack infected cells –Antiviral drugs Acyclovir Amantadine Azidothymidine (AZT) –Interferons: produced by cells when attacked (about 20)

13. Viral Replication Viral vaccines –Stimulation of immune response without risking pathogenic infection –Inactivated Chemically destroyed virus genome, capsid intact Example: Salk polio vaccine –Attenuated Live, but weakened virus Example: Sabin polio vaccine, chickenpox, MMR –Genetically engineered Production of viral proteins by recombinant organism Example: Hepatitis B vaccine

14. Viral Replication When viruses don’t replicate –Lysogeny Integration of viral genome into host’s genome Viral genome become dormant Integrated viral genome is known as provirus Human equivalent is retrovirus, HIV Typical for many plant viruses Figure 6.9: The formation of a provirus

15. Viral Replication Viroids and prions –Viroids Single-stranded RNA No capsid Infect plants –Prions Proteinaceous infectious particles No nucleic acid Cause mad cow disease Normal cellular protein Change in conformation creates Prion Results in spongiform encephalopathy Figure 6.11a: Stanley Prusiner, winner of 1997 Nobel in Physiology or Medicine for his work on prions as agents of infectious disease © Ulf Sirborn/AP Photos

16. Viruses and Cancer The development of cancer –Cancer Uncontrolled mitotic reproduction of cells Faster replication than normal cells Result is mass of cells called tumor –Benign tumors –Malignant tumors –Oncology –Dedifferentiation –Loss of contact inhibition –Modes of disease

17. Viruses and Cancer The involvement of viruses –Carcinogens –Some viruses can induce tumors –Examples Epstein-Barr virus Human T cell leukemia viruses (HTLVs) How viruses transform cells –Michael Bishop and Harold Varmus Oncogenes Proto-oncogenes How viruses may turn proto-oncogenes into oncogenes

18. Viruses and Cancer: How Viruses Transform Cells Figure 6.12: The oncogene theory