1. Origins of HIV Dr. Matthew Marsden, Ph.D. UCLA School of Medicine http://www.ck12.org/concept/HIV/

2. On http://aids.gov/hiv-aids-basics/hiv-aids-101/aids-timeline/ A new disease…

3. What is HIV? What is the difference between a virus and a bacteria? How is HIV transmitted? Basic characteristics of HIV disease course. Reasons for the rapid rate of HIV evolution. Where did HIV come from? When did HIV first jump into humans? http://pathmicro.med.sc.edu/lecture/hiv9.htm

4. What is HIV?

5. To understand what HIV and AIDS are, let’s break it down: Causative agent: H – Human – This particular virus can only infect human beings. I – Immunodeficiency – HIV weakens your immune system by destroying important cells that fight disease and infection. A "deficient" immune system can't protect you. V – Virus – A virus can only reproduce itself by taking over a cell in the body of its host. What is HIV?

6. To understand what HIV and AIDS are, let’s break it down: Causative agent: H – Human – This particular virus can only infect human beings. I – Immunodeficiency – HIV weakens your immune system by destroying important cells that fight disease and infection. A "deficient" immune system can't protect you. V – Virus – A virus can only reproduce itself by taking over a cell in the body of its host. http://aids.gov/hiv-aids-basics/hiv-aids-101/what-is-hiv-aids/ What is HIV? Disease: A – Acquired – AIDS is not something you inherit from your parents like eye color. You acquire AIDS. I – Immuno – Your body's immune system includes all the organs and cells that work to fight off infection or disease. D – Deficiency – You get AIDS when your immune system is "deficient," or isn't working the way it should. S – Syndrome – A syndrome is a collection of symptoms and signs of disease. AIDS is a syndrome, rather than a single disease. It is a complex illness with a wide range of symptoms.

7. What is HIV? Human immunodeficiency virus or HIV is a type of virus (from the Latin “virus” referring to poison). Viruses are: Small -Generally too small to see with a regular light microscope (20 - 400 nm diameter) If a cell was a football stadium then a small virus would be around the size of a football.

8. What is HIV? Human immunodeficiency virus or HIV is a type of virus (from the Latin “virus” referring to poison). Viruses are: Small -Generally too small to see with a regular light microscope (20 - 400 nm diameter) If a cell was a football stadium then a small virus would be around the size of a football. Can only replicate in living cells - Some can survive for long periods of time outside cells, but cannot replicate that way.

9. What is HIV? Human immunodeficiency virus or HIV is a type of virus (from the Latin “virus” referring to poison). Viruses are: Small -Generally too small to see with a regular light microscope (20 - 400 nm diameter) If a cell was a football stadium then a small virus would be around the size of a football. Can only replicate in living cells - Some can survive for long periods of time outside cells, but cannot replicate that way. Made up of Nucleic acids (DNA/RNA) and proteins -different from protein-only “prions” or nucleic acid-only “viroids”. Thousands of very different types of virus exist and HIV is a particular type termed a “retrovirus”.

10. What is the difference between a virus and a bacteria?

11. Bacteria Virus Ribosomes:PresentAbsent Living attributes:Living organismOpinions differ on whether viruses are a form of life, or organic structures that interact with living organisms. Number of cells:Unicellular; one cellNo cells Structures:DNA and RNA floating freely in cytoplasm. Cell wall and cell membrane DNA or RNA enclosed inside a coat of protein Enzymes:YesYes, in some Nucleus:No Can cause disease?:Yes How is it treated?:AntibioticsVaccines and antiviral medication. Reproduction:Fission- a form of asexual reproduction Invades a host cell and takes over the cell causing it to make copies of the viral DNA/RNA and proteins. Size:Larger (1000 nm)Smaller (20 – 400 nm) Modified from: http://www.diffen.com/difference/Bacteria_vs_Virushttp://www.diffen.com/difference/Bacteria_vs_Virus

12. http://pathmicro.med.sc.edu/mhunt/vir-size.jpg An average virus is much smaller than an average bacterium Relative size:

13. An average virus is much smaller than an average bacterium Virus Bacterium Image modified from: http://www.oucom.ohiou.edu/dbms-witmer/tarbosaurus_skull.htm: http://www.oucom.ohiou.edu/dbms-witmer/tarbosaurus_skull.htm Relative size:

14. http://tcf.epfl.ch/page-20833-en.html The HIV genome is composed of 9 genes, which encode 15 proteins. For comparison, the E. Coli bacterium contains around 4,377 genes and the human genome encodes around 21,000 genes. http://biology.kenyon.edu/slonc/ gene-web/Lentiviral/Lentivi2.html

15. How is HIV transmitted?

16. http://aids.gov

17. Basic characteristics of HIV disease course.

18. HIV is a virus that infects and destroys cells of the immune system (CD4+ cells). http://aids.gov/hiv-aids-basics/hiv-aids-101/what-is-hiv-aids/

19. HIV is a virus that infects and destroys cells of the immune system (CD4+ cells). Approximately 8-10 years Initial infection Asymptomatic period (clinical latency) AIDS Often (not always) accompanied by severe flu like symptoms: Opportunistic infections and cancer: AIDS (acquired immunodeficiency syndrome) is the late-stage HIV disease. This occurs when immune system becomes so damaged that it cannot fight off diseases and certain types of cancer. http://aids.gov/hiv-aids-basics/hiv-aids-101/what-is-hiv-aids/

20. Untreated HIV infection is a constant battle between the virus and the host immune system, with BILLIONS of new infected cells and virus particles produced and cleared EVERY DAY in each infected person. http://www.niaid.nih.gov/topics/HIVAIDS/Understanding/Biology/pages/clinicalcourse.aspx http://www.healthhype.com/cd4-count-dropping-viral-load-stable-in-hiv-infection-graph.html

21. Reasons for the rapid rate of HIV evolution.

22. HIV Life cycle http://preprod.www.tibotec.com/content/backgrounders/www.tibotec.com/hiv_lifecycle.html

23. HIV Life cycle http://preprod.www.tibotec.com/content/backgrounders/www.tibotec.com/hiv_lifecycle.html HIV mutates every time it replicates HIV replicates in billions of cells simultaneously every day HIV therefore evolves around 1 MILLION TIMES faster than mammalian genes

24. http://www.nature.com/embor/journal/v4/n6s/fig_tab/embor857_F1.html Comparison of HIV genetic variation with flu virus (longer lines mean more mutations)

25. http://www.nature.com/embor/journal/v4/n6s/fig_tab/embor857_F1.html Comparison of HIV genetic variation with flu virus (longer lines mean more mutations)

26. http://www.nature.com/embor/journal/v4/n6s/fig_tab/embor857_F1.html Comparison of HIV genetic variation with flu virus (longer lines mean more mutations)

27. http://www.nature.com/embor/journal/v4/n6s/fig_tab/embor857_F1.html Comparison of HIV genetic variation with flu virus (longer lines mean more mutations)

28. http://www.avert.org/hiv-types.htm HIV “family tree”

29. Where did HIV come from?

30. http://what-when-how.com/medical-microbiology-and-infection/zoonoses-systemic-infection/ Zoonosis = Cross-species transmission event

31. Phylogeny of lentiviruses. Sharp P M, and Hahn B H Cold Spring Harb Perspect Med 2011;1:a006841 ©2011 by Cold Spring Harbor Laboratory Press

32. Sharp P M, and Hahn B H Cold Spring Harb Perspect Med 2011;1:a006841

33. Where did HIV come from? HIV entered the human population from primates, which harbor a related virus known as SIV (simian immunodeficiency virus). This probably occurred during the butchering and consumption of monkey meat in Africa. http://www.avert.org/hiv-types.htm HIV “family tree”

34. Where did HIV come from? HIV entered the human population from primates, which harbor a related virus known as SIV (simian immunodeficiency virus). This probably occurred during the butchering and consumption of monkey meat in Africa. http://www.avert.org/hiv-types.htm HIV “family tree” http://www.awf.org/content/wildlife/detail/chimpanzee HIV-1 group M, which is the most prevalent HIV strain, jumped from chimpanzees into humans.

35. Where did HIV come from? HIV entered the human population from primates, which harbor a related virus known as SIV (simian immunodeficiency virus). This probably occurred during the butchering and consumption of monkey meat in Africa. http://www.avert.org/hiv-types.htm HIV “family tree” HIV-1 group M, which is the most prevalent HIV strain, jumped from chimpanzees into humans. http://www.awf.org/content/wildlife/detail/chimpanzee HIV-2 originated in sooty mangabeys and is responsible for fewer infections than HIV-1 New viruses are still being transferred from primates to humans, and have the potential to cause new diseases and epidemics. http://pin.primate.wisc.edu/factsh eets/entry/sooty_mangabey

38. Origins of human AIDS viruses. Sharp P M, and Hahn B H Cold Spring Harb Perspect Med 2011;1:a006841 ©2011 by Cold Spring Harbor Laboratory Press

40. Geographic distribution of SIVcpz and SIVgor infections in sub-Saharan Africa. Sharp P M, and Hahn B H Cold Spring Harb Perspect Med 2011;1:a006841 ©2011 by Cold Spring Harbor Laboratory Press

41. HIV-1 origins. Sharp P M, and Hahn B H Cold Spring Harb Perspect Med 2011;1:a006841 ©2011 by Cold Spring Harbor Laboratory Press

42. HIV-1 origins. Sharp P M, and Hahn B H Cold Spring Harb Perspect Med 2011;1:a006841 ©2011 by Cold Spring Harbor Laboratory Press Likely independent transmission events into humans

43. HIV-2 origins. Sharp P M, and Hahn B H Cold Spring Harb Perspect Med 2011;1:a006841 ©2011 by Cold Spring Harbor Laboratory Press

44. HIV-2 origins. Sharp P M, and Hahn B H Cold Spring Harb Perspect Med 2011;1:a006841 ©2011 by Cold Spring Harbor Laboratory Press Likely independent transmission events into humans

45. When did HIV first jump into humans?

46. M Worobey et al. Nature 455, 661-664 (2008) doi:10.1038/nature07390 Maximum clade credibility topology inferred using BEAST v1.4.7 under a Bayesian skyline plot tree prior.

47. The strain of HIV responsible for the majority of global infections (HIV-1 Group M) probably jumped into humans in western Africa sometime between 1884 and 1924. From there it then spread throughout the world.

48. Origin and Spread of HIV

49. Origins of HIV: Major take home points Different strains of HIV have been independently transmitted into humans from animals (Chimpanzee, Sooty mangabey, or Gorilla) on over 10 separate occasions. The most common strain of HIV (HIV-1, group M), which is responsible for over 90% of global infections, originated in chimpanzees (Pan troglodytes). This likely occurred in Cameroon (West Africa) approximately 100 years ago. Bushmeat (hunting monkeys for food) is the most likely source of these transmissions of AIDS viruses into humans.

50. General References: Sharp P M, and Hahn B H Cold Spring Harb Perspect Med 2011;1:a006841 Publication Date: August 1, 2013 | ISBN-10: 0199641145 | ISBN-13: 978-0199641147 | Edition: 1

51. More References: 1. Hybrid origin of SIV in Chimpanzees Bailes et al. Science 2003, 300:1713 2. Origins of HIV and the Evolution of Resistance to AIDS. Heeney et al. Science 2006, 313:462 3. Chimpanzee Reservoirs of Pandemic and Nonpandemic HIV-1 Keele et al. Science 2006, 313:523

52. Thank you for your attention! Questions?