Modeling Host-Parasite Coevolution: A Limited, Extremely Biased Perspective

Transcription

1 Modeling Host-Parasite Coevolution: A Limited, Extremely Biased Perspective Michael A. Gilchrist Dept. of Ecology & Evolutionary Biology University of Tennessee

2 Modeling Host-Parasite Coevolution Overview Previous Work Current Work Future Work

3 Modeling Host-Parasite Coevolution: Overview Need intuitive, evolvable parameters to describe H-P interaction Evolvable Parasite Parameters Antigen Type Replication rate Within-Host (Bacteria, fungi, metazoans) Within-Cell (Viruses) Target resource Cell type Tissue type

4 Modeling Host-Parasite Coevolution: Overview Evolvable Host Parameters Behavior Can affect mechanism and rate of exposure Immune Response Background level (inate immunity, naive CTL density) Sensitivity (ability to detect non-self vs. accidential triggering) Proliferation rate (activation of specific & non-specific IR) Sensitivity to resource/target cell loss

5 Modeling Host-Parasite Coevolution: Overview Nested Model Approach Meta-population Population Host Cell

6 Modeling Host-Parasite Coevolution: Overview Nested Model Approach Meta-population Population Host Cell

7 Modeling Host-Parasite Coevolution Overview Previous Work Current Work Future Work

8 Previous Work: Host-Parasite Coevolution Host Immune Response η Added Mortality Parasite Load P Transmission β Gilchrist & Sasaki (2002)

9 Immune response η dη dt = aηp a = Activation rate Parasite Load P dp = (b η)p dt b = Parasite birth rate η = Host immune response

10 Within-Host Dynamics Low Activation/Replication High Activation/Replication Time Time Parasite Load P Immune Response h Parasite Load P Immune Response h

11 Link Within-Host Dynamics to Between-Host Parameters Host Immune Response µ dη dt η aηp δ b P Added Mortality Parasite Load P b η c P Transmission β

12 Host Fitness Landscape and Optimal a vs. b Parasite Birth Rate b Host Immune Response a Rate

13 Parasite Fitness Landscape and Optimal a vs. b Parasite Birth Rate b Host Immune Response a Rate

14 Host-Parasite Coevolution Parasite Birth Rate b Host Immune Response a Rate

15 Host-Parasite Coevolution Parasite Birth Rate b Host Immune Response a Rate

16 Modeling Host-Parasite Coevolution Overview Previous Work Current Work Future Work

17 Current Work: Levels of Selection With Dan Coombs and Collen Ball Meta-population Population Host Cell

18 Levels of Selection: Conflict? Meta-population: low virulence Population: intermediate virulence Host: high virulence Cell: low virulence Meta-population Population Host Cell

19 Levels of Selection: Conflict? Meta-population: low virulence Population: intermediate virulence Host: high virulence Cell: low virulence Meta-population Population? Host Cell

20 Between-Host Model & Selection Epidemiological model of Susceptible and Infectious hosts ds/dt = b(s, I) βsi δs di/dt = βsi (α + δ)i Population b(s, I) birth S β Transmission I δ death δ α Virulence

21 Host Population: Between-Host Selection Natural selection favors the maximization of the reproductive ratio R: R = β α + δ = 1 Ŝ Strain which maximizes R Minimizes Ŝ Will competitively exclude other competitors. Bremermann & Pickering (1982), Anderson & May (1983)

22 Between-Host Model & Selection Maximizing R depends on relationship between β and α. Bremermann & Pickering (1982), Lenski & May (1994), Frank (1996) Transmission Β S 0 0 Α Virulence Α

23 Levels of Selection Between-Host Selection: Favors maximization of R Within-Host Selection:? Population Host

24 Within-Host Model & Selection dt/dt = λ k V T d T dt /dt = k V T (µ(p) + d)t dv/dt = p T c V, Infected Host λ cell production k T T V Infection d d µ(p) c clearance p

25 Within-Host Model: Two Strains Expand model to include second strain within a host dt/dt = λ k (V 1 + V 2 ) T d T dti /dt = k V i T (µ(p i ) + d)ti dv i /dt = p i T i c V i V T (0) = Inoculum Size = V 1 (0) + V 2 (0) x(0) = Initial Strain Mix = V 1(0) V T (0)

26 Within-Host Model: Two Strains Model Behavior 1 Density T 2 T 1 T V 1 V Time

27 Within-Host Model & Selection Equilibrium Behavior Equilibrium Density T V T Virion Production Rate p

28 Within-Host Model & Selection Within-host selection favors the maximization of the within-host reproductive ratio ρ: ρ = k c p µ(p) + d = 1ˆT Strain which maximizes ρ(p) Minimizes ˆT (p) Will competitively exclude other competitors within the host. Gilchrist et al. (2004)

29 Within-Host Model & Selection Min( ˆT (p )) = Within-Host Optimum Target Cell Density p T Within Host Fitness: Ρ Virion Production Rate p

30 Within-Host Model & Selection Maximizing ρ depends on relationship between µ & p. Coombs et al.(2003) Virion Production p S 0 0 p Cellular Virulence Μ

31 Levels of Selection Between-Host Selection: Favors maximization of R Within-Host Selection: Favors maximization of ρ Population? Host

32 Between Host Fitness: R Possible Conflict? Virion Production Rate p Within Host Fitness: Ρ

33 Nesting Models: Linking Within & Between-Host Nest model of within-host processes inside a model of between-host processes p T T V µ(p) S β I α

34 Nesting Models: Linking Within & Between-Host α(t ) = a 1 (T 0 T ) β(v ) = b 1 V p T T V µ(p) S β I α

35 Nesting Models: Linking Within & Between-Host Behavior Framework allows within-host virion production rate p and intial parasite mix x 0 to drive system Within-Host Dynamics Between-Host Parameters 1 Density T T V Rate Α Β Σ Time Time

36 Nesting Models: Transmission Assume inoculum reflects parasite mix at time of transmission x(a) = V 1 (a) V 1 (a) + V 2 (a)

37 Nesting Models: Between-Host Fitness Dynamics depends on virion production rates p 1 and p 2 as well as inoculum mix x 0.

38 Nesting Models: Between-Host Fitness Keep track of number of new infections ( ) with inoculum mixture x (0) = x(a) R `x 0 x 0 = Z 0 δ `x 0 x(a) β(v 1 (a), V 2 (a))exp» Z a 0 α(t (z))dz + δa da

39 Nesting Models: Between-Host Fitness R `x 0 x 0 = Z 0 δ `x 0 x(a) β(v 1, V 2 )e [ R a 0 α(t (z))dz+δa

40 Nesting Models: Between-Host Fitness NB: Dynamics depends on virion production rates p 1 and p 2 as well as inoculum mix x 0.

41 Nesting Models: Between- & Within-Host Fitness 1. Discretize inoculum mixes x = {x 1, x 2,... x n } 2. Calculate next generation operator R x(t + 1) = R x(t) where, R i,j = xi+x x i R(x, x)dx 3. Calculate equilibrium distribution of inocula x (dominant eigenvector)

42 Resolving Within & Between-Host Selection Examine three scenarios: Low: Exculsion > Spike Medium: Exclusion <=> Spike High: Exclusion < Spike sensitivity of virulence α to target cell T depletion Virulence Α High Sensitivity Medium Low Rate Σ: Medium Σ: High Σ: Low V 1 V 1 V 2 Β Target Cell Density: T T 0 Time

43 Dynamic Infection: Between Host Fitness Examine for different host sensitivities to resource loss (reduction in target cell density T )

44 Resolving Within & Between-Host Selection Examine three scenarios: Low: Exculsion > Spike Medium: Exclusion <=> Spike High: Exclusion < Spike sensitivity of virulence α to target cell T depletion Virulence Α High Sensitivity Medium Low Rate Σ: Medium Σ: High Σ: Low V 1 V 1 V 2 Β Target Cell Density: T T 0 Time

45 Resolving Within & Between-Host Selection Scenario: Low sensitivity to target cell T depletion Result: One limited region of coexistence

46 Resolving Within & Between-Host Selection Scenario: Medium sensitivity to target cell T depletion Result: Two distinct regions of coexistence

47 Resolving Within & Between-Host Selection Scenario: High sensitivity to target cell T depletion Result: One large region of coexistence

48 Resolving Within & Between-Host Selection Examine three scenarios: Low: Exculsion > Spike Medium: Exclusion <=> Spike High: Exclusion < Spike sensitivity of virulence α to target cell T depletion Virulence Α High Sensitivity Medium Low Rate Σ: Medium Σ: High Σ: Low V 1 V 1 V 2 Β Target Cell Density: T T 0 Time

49 Resolving Within & Between-Host Selection Conclusions Conflict in selection at Within- and Between Host scales Between Host Fitness: R Within Host Fitness: Ρ Virion Production Rate p

50 Resolving Within & Between-Host Selection Conclusions Nesting models allows us to examine conflict p T T V µ(p) S β I α

51 Resolving Within & Between-Host Selection Conclusions Range & behavior of coexistence depends on host sensitivity High Sensitivity Virulence Α Medium Low Target Cell Density: T T 0

52 Modeling Host-Parasite Coevolution Overview Previous Work Current Work Future Work

53 Future Work With Dan Coombs Add host immune response to model IR Trade-offs Proliferation vs. Time lag Sensitivity vs. Range of IR detection vs. Auto-immunity

54 Current Work: Levels of Selection Meta-population Population Host Cell

55 Financial Support Mike Gilchrist: University of Tennessee Dan Coombs & Collen Ball: NSERC & MITACS NCE.