What is a virus?

1. What is a virus? • “Genes in a suitcase” • Composition of a virus particle or virion: • Mode of replication: • Use host machineries for replication • Assemble in host cells Genes RNA or DNA Suitcase Protein shell Envelope Viral proteins Minimum requirement

2. Viruses vs. Bacteria

3. Human Immunodeficiency virus (HIV) • Retrovirus • Virion = • RNA genome • Capsid • Envelope (host) • Viral proteins Capsid RNA Envelope • causative agent for Acquired Immunodeficiency Syndrome (AIDS) • HIV (Virus) ≠ AIDS (Disease) • infects macrophages and CD4 T-lymphocytes • Virus life cycle: multi-step events, use host machinery

4. A global view of HIV infection in 2008: 33.4 million people living with HIV Note: This map represents 2007. Source: WHO/UNAIDS, 2008.

5. Please explain why the following statements are incorrect. HIV and AIDS is the same thing. There is a cure for HIV. In the absence of antiretroviral therapy, all individuals who are exposed to HIV will eventually progress to AIDS. Mosquito can transmit HIV.

6. What is the scientific process?

7. Individuals respond differently to HIV infection Exposed to HIV Antiretroviral therapy ~1% 5-10% 90-95% AIDS >10,000 copies RNA/mL “Progressor” No AIDS (<200 copies RNA/mL) “Intermediate Controller” No AIDS Undetectable viral RNA “Elite Controller” Do not require antiretroviral therapy Based on the observation, propose a hypothesis that explains the differences between the Progressors and Controllers. (Hint: think about what factor(s) maybe responsible for the development of AIDS in patients. Use information on the life cycle.) What method(s) will you use to test your hypothesis? What are you expected outcomes? Information obtained from Kaur and Mehra (2009) Tissue Antigens 73, 289–301

8. 11. Maturation Protease 1. Entry gp120, gp41 CD4, CCR5, CXCR4 10. Release Gag CD4-positive T-lymphocytes 9. Assembly Gag 2. Reverse transcription Reverse transcriptase 8. Translation ribosomes 3. Uncoating 7. RNA Export rev importins 4. Nuclear import 6. Transcription Tat Host transcription machineries 5. Integration Integrase, p32 Host proteins Viral proteins Figure was modified from Arhel N, Kirchhoff F. Biochim Biophys Acta. 2010

9. Host genetic vs. progression to AIDS • Genetic association study: progressors vs. controllers • Mutations on host proteins delay progression to AIDS (HIV controllers) • Entry receptors for HIV • CCR5∆32 M. Dean et al., Science 273, 1856 (1996). • C927T in CCR5 M. P. Martin et al., Science 282, 1907 (1998). • Val64Ile in CCR2 M. W. Smith et al., Science 277, 959 (1997). • Immune response against HIV • Major histocompatibility complex (MHC) class I - single nucleotide polymorphisms (SNPs) The International HIV controllers study, Science 330, 1551 (2010)

10. SNPs in many host factors involved in HIV infection could associate with AIDS progression Host factors that are important for the following host processes are also involved in HIV infection Information obtained from Arhel N, Kirchhoff F. Biochim Biophys Acta. 2010 How can we use host genetic information to help control HIV pandemic???

11. Challenges in controlling HIV pandemic What methods are used to prevent HIV infection or spread? Will SNPs information help prevent HIV infection in countries with high infection rate?

12. Other resources TWiv: This week in Virology Weekly Podcast about viruses http://www.twiv.tv/ CDC: Centers for Disease Control and Prevention http://cdc.gov/ ProMED The global electronic reporting system for outbreaks of emerging infectious diseases & toxins http://www.promedmail.org Institute for Molecular Virology UW Virology Resources: Labs, links, images http://www.virology.wisc.edu/ UNAIDS: Joint United Nations Programme on HIV/AIDS http://www.unaids.org/en/default.asp