Lecture 2 Evolution in action: the HIV virus

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1 Lecture 2 Evolution in action: the HIV virus

2 Peter and Rosemary Grant Barry Sinervo

3 The HIV/AIDS pandemic

4 Life expectancy in Botswana

5 What is HIV?

6 What is HIV? HIV is a retrovirus (i.e., RNA-based) with 9 genes

7 What is HIV? HIV is a retrovirus (i.e., RNA-based) with 9 genes is diploid (i.e., has 2 copies of each RNA strand)

8 The life cycle of HIV

9 Q: How does HIV cause AIDS?

10 Q: How does HIV cause AIDS? A: By attacking a key player in our immune system CD4 helper T cells.

11 The role of helper T cells in the immune response

12 The progression of an HIV infection

13 Changes in CD4 T-cell count during HIV infection

14 The life cycle of HIV

15 Natural selection, AZT, and the What is AZT? HIV virus

16 Natural selection, AZT, and the What is AZT? HIV virus AZT (azidothymidine) is a base analogue.

17 Structure of azidothymidine

18 Natural selection, AZT, and the What is AZT? HIV virus AZT (azidothymidine) is a base analogue. Incorporation of AZT (instead of T) by reverse transcriptase halts replication.

19 How AZT blocks reverse transcriptase

20 Evolution of AZT resistance

21 Resistance evolves in the polymerase s active site

22 Evolution of the HIV virus

23 Resistance to AZT has evolved in all patients taking the drug (usually in ~6 months)! This is an example of parallel evolution.

24 How does HIV evolve so rapidly?

25 How does HIV evolve so rapidly? 1. High mutation rate HIV s mutation rate is 10 6 higher than ours!

26 How does HIV evolve so rapidly? 1. High mutation rate HIV s mutation rate is 10 6 higher than ours! 2. Short generation time 1 year 300 viral generations.

27 How does HIV evolve so rapidly? 1. High mutation rate HIV s mutation rate is 10 6 higher than ours! 2. Short generation time 1 year 300 viral generations. 10 years of viral 2-3 x 10 6 years of evolution human evolution!

28 Evolution of HIV within an individual patient

29 Where did HIV come from?

30 Phylogeny of HIV-1 and related viruses

31 Where did HIV come from? HIV jumped to humans multiple times from different primate hosts.

32 Where did HIV come from? HIV jumped to humans multiple times from different primate hosts. Inter-species transfers of infectious diseases are called zoonoses.

33 Other examples of zoonoses Malaria (P. falciparum) Marburg fever Cholera Leishmaniasis Plague Hantavirus Dengue fever Toxoplasmosis H1N1 swine flu Rabies Ebola Ringworms SARS Cowpox West Nile virus Lyme disease Creutzfeldt-Jakob disease Yellow fever

34 Human Plasmodium falciparum Chimpanzee Plasmodium spp. see Rich et al. Proc. Natl. Acad. Sci. U.S.A. 106: 14902

35 Dating the origin of HIV-1 in humans

36 Dating the origin of HIV-1 in humans

37 Dating the origin of HIV-1 in humans

38 Q: Why is HIV infection usually fatal?

39 Q: How do viruses achieve reproductive success?

40 Q: How do viruses achieve reproductive success? à 1. Infect host

41 Q: How do viruses achieve reproductive success? à 1. Infect host 2. Reproduce within host

42 Q: How do viruses achieve reproductive success? à à 1. Infect host 2. Reproduce within host 3. Infect new host

43 Q: How do viruses achieve reproductive success? à à 1. Infect host 2. Reproduce within host 3. Infect new host

44 Strategy 1: Reproduce rapidly within host

45 Strategy 1: Reproduce rapidly within host Chance of infecting new host Host viability

46 Strategy 1: Reproduce rapidly within host Chance of infecting new host Host viability Strategy 2: Reproduce slowly within host

47 Strategy 1: Reproduce rapidly within host Chance of infecting new host Host viability Strategy 2: Reproduce slowly within host Chance of infecting new host Host viability

48 Q: Why is HIV infection usually fatal?

49 Q: Why is HIV infection usually fatal? A: Because the virus is short- sighted

50 Q: Why is HIV infection usually fatal? A: Because the virus is short- sighted - lethal strains predominate because of a shortterm advantage in survival and reproduction.

51 Q: Why has a vaccine for HIV-1 not been successfully developed?

52 Q: Why has a vaccine for HIV-1 not been successfully developed? A1: Because the virus evolves very rapidly.

53 Q: Why has a vaccine for HIV-1 not been successfully developed? A1: Because the virus evolves very rapidly. A2: Because of HIV-1 strain diversity.

54 Distribution of HIV-1 major clades

55 The CCR5-Δ32 allele confers resistance to HIV infection

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