Evolution of virulence

Conventional wisdom “Given enough time a state of peaceful coexistence eventually becomes established between any host and parasite.” –Rene Dubos (1965) “Disease usually represents the inconclusive negotiation for symbiosis…a biological misinterpretation of borders.” –Lewis Thomas (1972) “The ideal of parasitism is actually commensalism” -Paul D. Hoeprich (1989)

Pathogens have an evolutionary edge Rapid replication rate relative to host Many mechanisms of increasing genetic variability Sporulation and biofilms –Long-term durability in the environment

Segmented genome with recombining fragments Variable repeats, e.g. ATATATATATAT Cassette switching (Neisseria, trypanosomes) Mechanisms of variation Plasmids and viruses “Competence” = picking up foreign DNA from environment

Parasite fitness is dependent upon transmission to susceptible hosts

Why virulence evolves Correlation between replication rate of pathogen and harm to host (presumed, poorly supported) Faster replication = better competition within hosts Slower replication = better competition between hosts?? –Is this an evolutionarily stable strategy (ESS?)

Survey of parasite strategies Direct transmission (host-to-host contact) Vectorborne (versus direct transmission) –Malaria, dengue, sleeping sickness, etc etc Vertical transmission (versus horizontal) –Lots of plant pathogens transmitted through seed “Sit and wait” (durable pathogens) –Anthrax, baculoviruses

Survey of parasite strategies II Intracellular immune avoidance –Mycobacterium tuberculosis and M. leprae –Legionella –Rickettssia pathogens (e.g typhus, Rocky Mtn spotted fever) Waterborne transmission –Diarrheal pathogens Attendant-borne transmission –Group B Strep, Staph (esp. MRSA), Serratia, Klebsiella –Canine parvovirus –Agricultural pathogens (Cadang-cadang, Ilarviruses)

Parasite fitness is dependent upon transmission to susceptible hosts Each of these strategies offer distinct evolutionary predictions

Is the current host-pathogen relationship optimal from the parasite’s perspective? Alternative hypotheses (sensu Ewald 1994):  Restricted adaptation (insufficient time)  Adaptive severity Mode of transmission –Is host mobility critical for transmission or not?

Why virulence may increase when hosts are dense (i) The extinction rate of virulent lineages may decline because ‘herd immunity’ is less likely to reduce the pool of susceptibles below a critical transmission threshold for parasite maintenance (Fine 1993). (ii) High host density may reduce the dependence on host mobility for transmission and permit greater host exploitation (Ewald 1994; Lenski & May 1994). (iii) Virulent variants may gain a numerical advantage during epidemic spread because of more frequent transmission (Anderson 1991). (iv) Transmission during the early stage of an infection may be enhanced.

Timing of transmission and the evolution of virulence of an insect virus System: Lymantria dispar (gypsy moth) NPV Experimenters: 3 consecutive years of Amherst College undergraduate honors students Treatments: Early versus Late Transmission Transmission simulated early versus late, 9 cycles of transmission

Early LateGypchek * Percent larval morality Viruses transmitted early became more lethal

Viruses transmitted late were more productive

Group selection and interparasite conflict Superinfection = two strains of the same pathogen co-infecting and competing within the same host Between host competition = parasite populations within different hosts will compete over the longer term –Parasites within hosts, while related, will still act selfishly given sufficient genetic variance These two dynamics may play against each other in an ecological “metapopulation” setting