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Evolution and transmission in HIV
Steve Paterson Review; Rambaut 2004 Nature Reviews Genetics 5: 52-61 ‘The causes and consequences of HIV evolution’
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Use phylogenies to follow infection
HIV is an RNA virus, with a high mutation rate mutates over course of infection
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HIV
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HIV Gag gene polymorphism
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Phylogenetic tree should mirror contact structure of infection
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Molecular epidemiology of HIV in Edinburgh
HIV mutates as passes from one individual to next Use substitutions to build phylogenies and track pattern of infection
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HIV phylogeny Holmes et al (1994) J. Inf. Diseases 171:45-53
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Oliveira et al (2006) Nature. 444, 836-837
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Origins of HIV HIV-2 HIV-1
Rambaut 2004 Nature Reviews Genetics 5: 52-61
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Origins of HIV-1
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Within host evolution of HIV
high rate of mutation (0.2 errors/genome) high rate of replication (gen. time = 2.5 days, virions/day) natural selection immune selection genetic drift
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Genetic diversity of HIV
Rambaut (2004) Nature Reviews Genetics 5, 52-61
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Evolution of drug resistance in HIV
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env gene Long-lived Short-lived CTL escape blue sites = +ve seln.
Ross (2002) J. Virol. 76 : Immune pressure, effective at driving amino-acid change in long-lived patients?
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