Understanding Virology: Protein & Genome Synthesis Details

1. Virology - Chapter 13 Not responsible for details of Protein & genome synthesis pp 399-401 A little history… “Filterable viruses” Bacteriophages Wendell Stanley and TMV 1935 Advent of electron microscopy Small pox virus in cell Crystalized polio virus How small

2. Fundamental Properties of Viruses 1) no metabolism 2) obligate intracellular pathogens 3) no membrane transport 4) replicate by “self-assembly” 5) genome of RNA or DNA Classification of viruses -- Not included in Kingdom system -- Not classified above Order Naming  key trait of group member -- Herpesviridae (‘herpes’ like viruess) -- Filovirodae (‘filament’ like viruses Sizes and surfaces of some viruses

3. Virus Structure The protein “capsid” Common capsid shapes rod (helical) icosahedron Capsomeres Human rhinovirus poliovirus Virology and AIDS

4. Some more complex viruses Enveloped viruses HIV structure Bacteriophages Herpes virus Receptors Influenza virus

5. Influenza (in chapter 22) Key surface antigens Hemaglutinin – H Neuraminidase – N -- numbered 1,2,3, etc -- H3N2, H1N1, H1N5, H & N antigens change types periodically Minor genetic changes  seasonal flu Major genetic changes  pandemic flu ??

6. Seasonal ‘Flu’ ~36K deaths ~200,000 hospitalizations Why is there a ‘Flu season’?: social interactions environmental conditions Spread of new forms H and N change slightly annually -- slightly different forms of viruses -- different “mixes” of forms = “Antigenic drift” -- minor mutations in H and N genes

7. Pandemic Influenza “Antigenic-Shift” can occur -- DNA segments recombine -- in animal hosts Challenges to control Vaccine development time Production capacity Distribution Economics

8. How do viruses enter cells? Bacteriophages animal viruses membrane fusion vs endocytosis uncoating T4 infection Modes of cell entry Influenza penetration Virology and AIDS

9. How do viruses replicate • inside of cells? • The simple way – “Lytic cycle” Measles virus Bacteriophage

10. Viral replication type 2 “Lysogenic cycle” Viral DNA becomes part of host cell DNA Latency Some diseases caused by lysogenic viruses Herpes Rubella Chickenpox HPV infections Measles Mumps Hepatitis HIV Ancient infections = ~ 8% of human genome

11. Viruses and latency Herpes (Herpes simplex virus) HSV-I : oral fever blisters HSV-II: genital herpes Induction Chickenpox (varicella-zoster virus) -- similarities to Herpes HSV infection

12. How can viruses cause cancer? Human papilloma viruses warts cervical cancer Hepatitis B and C liver cancer Epstein-Barr ‘Mono’ (-nucleosis) lymphoma/leukemia Oncogenes Chronic inflammation Virology and AIDS

13. HIV and AIDS Virus anatomy Target cells -- T-cells, etc

14. HIV uses lysogenic cycle, but… …it’s a “Retrovirus” Reverse transcriptase RNA DNA high mutational rates CD4 & coreceptors T-cells & macrophages Stages of infection Integrase and Protease HIV replication & Drugs

15. What are the clinical stages of an HIV infection? Stages of disease 1. Acute Phase 2. Chronic Phase 3. AIDS -- T-cells < 200 /mm3 -- AIDS-associated disease(s) Opportunistic diseases Primary infection 1 5 Clinical latency 4 2 3 HIV in blood CD4 (helper) T cell count Antibody against HIV Virology and AIDS

16. AIDS-associated diseases Virology and AIDS

17. Control of viral infections (or lack thereof) Antibiotics don’t work Synthetic drugs -- symptoms -- low replication Anti-HIV therapy 1) reverse transcriptase inhibitors -- AZT, ddl, ddc, etc -- nucleotide analogs 2) protease inhibitors 3) combinational drug therapy What about an AIDS vaccine?? Virology and AIDS

18. AIDS Epidemiology Prevalence (vs Incidence) HIV Clades A, B, C, etc Transmission Cost of AIDS drugs Health care issues HIV prevalence (WHO 2010) Virology and AIDS

19. Viroids and Prions ‘molecular pathogens’ Viriods potato tuber spindle virus (it isn’t) replication Prions TSE: transmissable spongiform encephalopathy Scrapie Kuru BSE: Mad cow disease Virology and AIDS