Lecture 2 Evolution in action: the HIV virus
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1 Lecture 2 Evolution in action: the HIV virus
2 The HIV/AIDS pandemic
3 Life expectancy in Botswana
4 What is HIV?
5 What is HIV? HIV is a retrovirus (i.e., RNA-based) with 9 genes
6 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)
7 The life cycle of HIV
8 Q: How does HIV cause AIDS?
9 Q: How does HIV cause AIDS? A: By attacking a key player in our immune system CD4 helper T cells.
10 The role of helper T cells in the immune response
11 The progression of an HIV infection
12 Changes in CD4 T-cell count during HIV infection
13 The life cycle of HIV
14 Natural selection, AZT, and the What is AZT? HIV virus
15 Natural selection, AZT, and the What is AZT? HIV virus AZT (azidothymidine) is a base analogue.
16 Structure of azidothymidine
17 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.
18 How AZT blocks reverse transcriptase
19 Evolution of AZT resistance
20 Resistance evolves in the polymerase s active site
21 Evolution of the HIV virus
22 Resistance to AZT has evolved in all patients taking the drug (usually in ~6 months)! This is an example of parallel evolution.
23 How does HIV evolve so rapidly?
24 How does HIV evolve so rapidly? 1. High mutation rate HIV s mutation rate is 10 6 higher than ours!
25 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.
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. 10 years of viral 2-3 x 10 6 years of evolution human evolution!
27 Evolution of HIV within an individual patient
28 Where did HIV come from?
29 Phylogeny of HIV-1 and related viruses
30 Where did HIV come from? HIV jumped to humans multiple times from different primate hosts.
31 Where did HIV come from? HIV jumped to humans multiple times from different primate hosts. Inter-species transfers of infectious diseases are called zoonoses.
32 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
33 Human Plasmodium falciparum Chimpanzee Plasmodium spp. see Rich et al. Proc. Natl. Acad. Sci. U.S.A. 106: 14902
34 Dating the origin of HIV-1 in humans
35 Dating the origin of HIV-1 in humans
36 Dating the origin of HIV-1 in humans
37 Q: Why is HIV infection usually fatal?
38 Q: How do viruses achieve reproductive success?
39 Q: How do viruses achieve reproductive success? 1. Infect host
40 Q: How do viruses achieve reproductive success? 1. Infect host 2. Reproduce within host
41 Q: How do viruses achieve reproductive success? 1. Infect host 2. Reproduce within host 3. Infect new host
42 Q: How do viruses achieve reproductive success? 1. Infect host 2. Reproduce within host 3. Infect new host
43 Strategy 1: Reproduce rapidly within host
44 Strategy 1: Reproduce rapidly within host Chance of infecting new host Host viability
45 Strategy 1: Reproduce rapidly within host Chance of infecting new host Host viability Strategy 2: Reproduce slowly within host
46 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
47 Q: Why is HIV infection usually fatal?
48 Q: Why is HIV infection usually fatal? A: Because the virus is short- sighted
49 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.
50 Q: Why has a vaccine for HIV-1 not been successfully developed?
51 Q: Why has a vaccine for HIV-1 not been successfully developed? A1: Because the virus evolves very rapidly.
52 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.
53 Distribution of HIV-1 major clades
54 The CCR5-Δ32 allele confers resistance to HIV infection
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