Evolution and Human HealthEvolving Pathogens: Evasion of the host’s immune responseInfluenza A virus – 1Influenza A virus – 2Influenza A virus (Fig. 13.3)Evolution of hemagglutinin genes in influenza A (Fitch et al. 1991) – 1Evolution of hemagglutinin genes in influenza A (Fitch et al. 1991) – 2Evolution of hemagglutinin genes in influenza A (Fitch et al. 1991) (Fig. 13.4)The origin of pandemic flu strainsPhylogeny of influenza A viruses based on the nucleoprotein gene (Fig. 13.5) – 1Phylogeny of influenza A viruses based on the nucleoprotein gene (Fig. 13.5) – 2Phylogeny of influenza A viruses based on the nucleoprotein gene (Fig. 13.5) – 3Phylogeny of influenza A viruses based on the hemagglu-tinin gene (Fig. 13.6) (part)Evolving Pathogens: antibiotic resistancePenicillin resistance among Pneumococcus bacteria in Icelandic children (Austin et al. 1999) (Fig. 13.7)Costs to bacteria of antibiotic resistanceStreptomycin resistance in E. coliCost of resistance to streptomycin in E. coli (Schrag et al. 1997) (Fig. 13.8) – 1Cost of resistance to streptomycin in E. coli (Schrag et al. 1997) (Fig. 13.8) – 2 (a) Short-term cost of resistance (b) Long-term “cost” of resistanceEvolving pathogens: virulenceHow virulence evolves – 1How virulence evolves – 2How virulence evolves – 3Evolution of virulence in bacteriophage F1 in cultures of E. coli (Messenger et al. 1999)Evolution of virulence in bacteriophage F1 in cultures of E. coli (Messenger et al. 1999) (Fig. 13.9)Virulence in human pathogens – 1The virulence of vector-borne versus directly transmitted diseases (Ewald 1994)Virulence in human pathogens – 2The virulence of intestinal bacteria as a function of the tendency toward waterborne transmission (Ewald 1991) (Fig. 13.11)Tissues as evolving populations of cellsA case study of adenosine deaminase (ADA) deficiency (Hirschorn et al. 1996) — 1A case study of adenosine deaminase (ADA) deficiency (Hirschorn et al. 1996) — 2A case study of adenosine deaminase (ADA) deficiency (Hirschorn et al. 1996) — 3A case study of adenosine deaminase (ADA) deficiency (Hirschorn et al. 1996) — 41Evolution and Human HealthChapter 132Evolving Pathogens: Evasion of the host’s immune responseInfluenza A virus3Influenza A virus – 1•Responsible for annual flu epidemics and occasional global pandemics (1918, 1957, 1968)•Kills ~20,000 Americans per year•1918 pandemic sickened ~20% of world population, killed 50 – 100 million people4Influenza A virus – 2•Genome of 8 RNA strands, that encode 10 proteins•Predominant coat protein is hemagglutinin:– responsible for binding to host cell–major viral protein that is recognized, attacked and remembered by host immune system–Antigenic sites are those specific parts of hemagglutinin that are recognized and remembered by the immune system5Influenza A virus (Fig. 13.3)6Evolution of hemagglutinin genes in influenza A (Fitch et al. 1991) – 1•Strains isolated from humans between 1968 and 1987 and stored in freezers•Virus evolves about 1 million times faster than mammals•109 amino acid replacements observed–In surviving (1987) strain 33 amino acid replacements were in antigenic sites vs. 10 replacements in non-antigenic sites–In extinct lineages, the ratio of antigenic to non-antigenic site replacements was 31 to 357Evolution of hemagglutinin genes in influenza A (Fitch et al. 1991) – 2•18 codons in the hemagglutinin gene showed an excess of nonsynonymous over synonymous substitutions – evidence of positive selection for viral fitness (pathogenicity)•This fact allows prediction of the flu strain that is most likely to cause the next annual outbreak - look for the circulating strain that has the most mutations in the 18 codons known to be under positive selection–correct 9 of 11 times8Evolution of hemagglutinin genes in influenza A (Fitch et al. 1991) (Fig. 13.4)9The origin of pandemic flu strains•Influenza strains are designated by the groups to which their hemagglutinin and neuraminidase coat proteins belong•H3N2 mean hemagglutinin-3, neuraminidase-2•Before 1968 was H3 was unknown in human flu strains — where did it come from?•Evidence strongly supports the idea that flu strains can move between humans, birds and pigs.•When two strains simultaneously infect a cell, they can “recombine” their RNA genomes•H3 gene apparently entered humans from birds and this new human strain was responsible for the 1968 pandemic10Phylogeny of influenza A viruses based on the nucleoprotein gene (Fig. 13.5) – 1Letter and numbers in parentheses indicate subtypes based on groups of hemagglutinin and neuraminidase, e.g., H2N3 is hemagglutinin-2, neuraminidase-311Phylogeny of influenza A viruses based on the nucleoprotein gene (Fig. 13.5) – 2Letter and numbers in parentheses indicate subtypes based on groups of hemagglutinin and neuraminidase, e.g., H2N3 is hemagglutinin-2, neuraminidase-312Phylogeny of influenza A viruses based on the nucleoprotein gene (Fig. 13.5) – 3Letter and numbers in parentheses indicate subtypes based on groups of hemagglutinin and neuraminidase, e.g., H2N3 is hemagglutinin-2, neuraminidase-313Phylogeny of influenza A viruses based on the hemagglu-tinin gene (Fig. 13.6) (part)Letter and numbers in parentheses indicate subtypes based on groups of hemagglutinin and neuraminidase, e.g., H2N3 is hemagglutinin-2, neuraminidase-314Evolving Pathogens: antibiotic resistance•Antibiotics exert strong selective pressure on bacteria to evolve resistance•Penicillin resistance by Pneumococcus bacteria in children in Iceland–Frequency of resistant bacteria increased 1998 - 93, and then decreased after penicillin use was discouraged15Penicillin resistance among Pneumococcus bacteria in Icelandic children (Austin et al. 1999) (Fig. 13.7)16Costs to bacteria of antibiotic resistance•It is widely assumed that the evolution of antibiotic resistance by bacteria incurs a fitness cost in the absence of antibiotic (remember HIV and AZT resistance)•This is often, but not always, the case•Compensatory mutations may reduce the cost of resistance17Streptomycin resistance in E. coli•Streptomycin interferes with protein synthesis by binding to a ribosomal protein encoded by the rpsL gene•Point mutations to the rpsL gene confer resistance to streptomycin•Schrag et al. (1997) evaluated the costs of streptomycin resistance, and the ability of E. coli to evolve compensatory