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Emergence of elevated levels of
multiple infection in spatial host-
virus dynamics
Bradford Taylor1, Catherine Penington2, Joshua Weitz3,1
1School of Physics and 3School of Biology, Georgia Institute of Technology
2School of Mathematical Sciences, Queensland University of Technology
http://ecotheory.biology.gatech.edu
Quantitative Laws II
Multiple infection allows
intracellular interactions between
viruses
La Scola et al,
Nature (2008)
Coinfection alters ecological parameters
Multiple infections alter
evolutionary rates due to shared
resources
Recombination vs. Complementation
Multiple infection rates are
unknown in vivo
How does space affect:
 the distribution of multiplicity of
infection (MOI)?
RM Donlan,
Emerg infect dis, 2002
Adsorption mediates clustering
Low adsorption
High adsorption
Well-mixed model dynamics
Host
Infected
hosts
Viruses
Well-mixed model yields geometric
MOI distribution
Host
Infected
hosts
Viruses
Geometric distribution for MOI
MOI distribution follows geometric
distribution for low adsorption
Viruses
0
[1 5]
[6 10]
[11 15]
[16 20]
>20
Hosts
E
H
I1
C
Clustered MOI distributions feature
fat tails
Hosts
E
H
I1
C
Viruses
0
[1 5]
[6 10]
[11 15]
[16 20]
>20
How many viruses are colocated
with a host of a specific MOI?
MOI Layer (internal viruses) Viral Layer (external viruses)
11
How many viruses are colocated
with a host of a specific MOI?
MOI Layer (internal viruses) Viral Layer (external viruses)
12
How many viruses are colocated
with a host of a specific MOI?
MOI Layer (internal viruses) Viral Layer (external viruses)
1
13
How many viruses are colocated
with a host of a specific MOI?
MOI Layer (internal viruses) Viral Layer (external viruses)
1 2
14
Random dispersal gives Poisson
distribution of viruses
0 5 10
Local Viruses
0
0.2
0.4
0.6
0.8
1
ProbabilityDensity
0 5 10
Local Viruses
0
0.2
0.4
0.6
0.8
1
ProbabilityDensity
15
No clustering clustering
0 5 10
Local Viruses
0
0.2
0.4
0.6
0.8
1
ProbabilityDensity
MOI =0
0 5 10
Local Viruses
0
0.2
0.4
0.6
0.8
1
ProbabilityDensity
MOI =0
Clustered Viral distribution skew
right with increasing MOI16
No clustering clustering
0 5 10
Local Viruses
0
0.2
0.4
0.6
0.8
1
ProbabilityDensity
MOI =0
MOI =1
0 5 10
Local Viruses
0
0.2
0.4
0.6
0.8
1
ProbabilityDensity
MOI =0
MOI =1
Clustered Viral distribution skew
right with increasing MOI17
No clustering clustering
0 5 10
Local Viruses
0
0.2
0.4
0.6
0.8
1
ProbabilityDensity
MOI =0
MOI =1
MOI =2
0 5 10
Local Viruses
0
0.2
0.4
0.6
0.8
1
ProbabilityDensity
MOI =0
MOI =1
MOI =2
Clustered Viral distribution skew
right with increasing MOI18
No clustering clustering
0 5 10
Local Viruses
0
0.2
0.4
0.6
0.8
1
ProbabilityDensity
MOI =0
MOI =1
MOI =2
MOI =3
0 5 10
Local Viruses
0
0.2
0.4
0.6
0.8
1
ProbabilityDensity
MOI =0
MOI =1
MOI =2
MOI =3
Clustered Viral distribution skew
right with increasing MOI19
No clustering clustering
0 5 10
Local Viruses
0
0.2
0.4
0.6
0.8
1
ProbabilityDensity
MOI =0
MOI =1
MOI =2
MOI =3
MOI =4
MOI =5
MOI =6
0 5 10
Local Viruses
0
0.2
0.4
0.6
0.8
1
ProbabilityDensity
MOI =0
MOI =1
MOI =2
MOI =3
MOI =4
MOI =5
MOI =6
Clustered Viral distribution skew
right with increasing MOI20
No clustering clustering
Well-mixed model yields geometric
MOI distribution
Host
Infected
hosts
Viruses
Deviates from geometric distribution
Clustered MOI distributions feature
fat tails
Hosts
E
H
I1
C
Viruses
0
[1 5]
[6 10]
[11 15]
[16 20]
>20
Multiple infection dynamics driven
by invasions of clusters
Invasions of larger clusters skews
viral distributions
Viruses
0 5 10
Probabilitydensity
0
0.2
0.4
0.6
0.8
1
<Viral Distribution> MOI =1
R=3
R=4
R=5
R=7
R=10
24
Invasions of larger clusters skews
viral distributions
Viruses
0 5 10
Probabilitydensity
0
0.2
0.4
0.6
0.8
1
<Viral Distribution> MOI =2
R=3
R=4
R=5
R=7
R=10
Viruses
0 5 10
Probabilitydensity
0
0.2
0.4
0.6
0.8
1
<Viral Distribution> MOI =3
R=3
R=4
R=5
R=7
R=10
Viruses
0 5 10
Probabilitydensity
0
0.2
0.4
0.6
0.8
1
<Viral Distribution> MOI =1
R=3
R=4
R=5
R=7
R=10
25
Conclusions
 High adsorption leads to clustering
 Clustering leads to fat tails in MOI distribution
 Cluster invasions drive the dynamics to skew
MOI distributions
Future work: spatial models of
Virophage—viruses of viruses
Taylor et al,
JTB (2014)
Paired Entry Mode (PEM)
Independent Entry Mode (IEM)
Desnues et al. PNAS
(2012)
Fischer and Suttle
Science (2011)
Acknowledgements
 Weitz Lab (GaTech)
 Funding:
 Quantitative Laws II
 NSF Physics of Living Systems
 James S Mcdonnell Foundation
 Nerem Fellowship
 Burroughs Wellcome Fund
Acknowledgements
Questions?
Hosts
E
H
I1
C
Viruses
0
[1 5]
[6 10]
[11 15]
[16 20]
>20
BP Taylor, CJ Penington, JS W
bioRxiv: 048876
 Weitz Lab (GaTech)
 Funding:
 Quantitative Laws II
 NSF Physics of Living Systems
 James S Mcdonnell Foundation
 Nerem Fellowship
 Burroughs Wellcome Fund
Analogous PDE model
31
Parametrize based on
prochlorococcus
single
time step
System size: 500 x 500 lattice pts=¼ ml
32
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Emergence of elevated levels of multiple infection in spatial host-virus dynamics - Bradford Taylor

  • 1. Emergence of elevated levels of multiple infection in spatial host- virus dynamics Bradford Taylor1, Catherine Penington2, Joshua Weitz3,1 1School of Physics and 3School of Biology, Georgia Institute of Technology 2School of Mathematical Sciences, Queensland University of Technology http://ecotheory.biology.gatech.edu Quantitative Laws II
  • 2. Multiple infection allows intracellular interactions between viruses La Scola et al, Nature (2008) Coinfection alters ecological parameters
  • 3. Multiple infections alter evolutionary rates due to shared resources Recombination vs. Complementation
  • 4. Multiple infection rates are unknown in vivo
  • 5. How does space affect:  the distribution of multiplicity of infection (MOI)? RM Donlan, Emerg infect dis, 2002
  • 6. Adsorption mediates clustering Low adsorption High adsorption
  • 8. Well-mixed model yields geometric MOI distribution Host Infected hosts Viruses Geometric distribution for MOI
  • 9. MOI distribution follows geometric distribution for low adsorption Viruses 0 [1 5] [6 10] [11 15] [16 20] >20 Hosts E H I1 C
  • 10. Clustered MOI distributions feature fat tails Hosts E H I1 C Viruses 0 [1 5] [6 10] [11 15] [16 20] >20
  • 11. How many viruses are colocated with a host of a specific MOI? MOI Layer (internal viruses) Viral Layer (external viruses) 11
  • 12. How many viruses are colocated with a host of a specific MOI? MOI Layer (internal viruses) Viral Layer (external viruses) 12
  • 13. How many viruses are colocated with a host of a specific MOI? MOI Layer (internal viruses) Viral Layer (external viruses) 1 13
  • 14. How many viruses are colocated with a host of a specific MOI? MOI Layer (internal viruses) Viral Layer (external viruses) 1 2 14
  • 15. Random dispersal gives Poisson distribution of viruses 0 5 10 Local Viruses 0 0.2 0.4 0.6 0.8 1 ProbabilityDensity 0 5 10 Local Viruses 0 0.2 0.4 0.6 0.8 1 ProbabilityDensity 15 No clustering clustering
  • 16. 0 5 10 Local Viruses 0 0.2 0.4 0.6 0.8 1 ProbabilityDensity MOI =0 0 5 10 Local Viruses 0 0.2 0.4 0.6 0.8 1 ProbabilityDensity MOI =0 Clustered Viral distribution skew right with increasing MOI16 No clustering clustering
  • 17. 0 5 10 Local Viruses 0 0.2 0.4 0.6 0.8 1 ProbabilityDensity MOI =0 MOI =1 0 5 10 Local Viruses 0 0.2 0.4 0.6 0.8 1 ProbabilityDensity MOI =0 MOI =1 Clustered Viral distribution skew right with increasing MOI17 No clustering clustering
  • 18. 0 5 10 Local Viruses 0 0.2 0.4 0.6 0.8 1 ProbabilityDensity MOI =0 MOI =1 MOI =2 0 5 10 Local Viruses 0 0.2 0.4 0.6 0.8 1 ProbabilityDensity MOI =0 MOI =1 MOI =2 Clustered Viral distribution skew right with increasing MOI18 No clustering clustering
  • 19. 0 5 10 Local Viruses 0 0.2 0.4 0.6 0.8 1 ProbabilityDensity MOI =0 MOI =1 MOI =2 MOI =3 0 5 10 Local Viruses 0 0.2 0.4 0.6 0.8 1 ProbabilityDensity MOI =0 MOI =1 MOI =2 MOI =3 Clustered Viral distribution skew right with increasing MOI19 No clustering clustering
  • 20. 0 5 10 Local Viruses 0 0.2 0.4 0.6 0.8 1 ProbabilityDensity MOI =0 MOI =1 MOI =2 MOI =3 MOI =4 MOI =5 MOI =6 0 5 10 Local Viruses 0 0.2 0.4 0.6 0.8 1 ProbabilityDensity MOI =0 MOI =1 MOI =2 MOI =3 MOI =4 MOI =5 MOI =6 Clustered Viral distribution skew right with increasing MOI20 No clustering clustering
  • 21. Well-mixed model yields geometric MOI distribution Host Infected hosts Viruses Deviates from geometric distribution
  • 22. Clustered MOI distributions feature fat tails Hosts E H I1 C Viruses 0 [1 5] [6 10] [11 15] [16 20] >20
  • 23. Multiple infection dynamics driven by invasions of clusters
  • 24. Invasions of larger clusters skews viral distributions Viruses 0 5 10 Probabilitydensity 0 0.2 0.4 0.6 0.8 1 <Viral Distribution> MOI =1 R=3 R=4 R=5 R=7 R=10 24
  • 25. Invasions of larger clusters skews viral distributions Viruses 0 5 10 Probabilitydensity 0 0.2 0.4 0.6 0.8 1 <Viral Distribution> MOI =2 R=3 R=4 R=5 R=7 R=10 Viruses 0 5 10 Probabilitydensity 0 0.2 0.4 0.6 0.8 1 <Viral Distribution> MOI =3 R=3 R=4 R=5 R=7 R=10 Viruses 0 5 10 Probabilitydensity 0 0.2 0.4 0.6 0.8 1 <Viral Distribution> MOI =1 R=3 R=4 R=5 R=7 R=10 25
  • 26. Conclusions  High adsorption leads to clustering  Clustering leads to fat tails in MOI distribution  Cluster invasions drive the dynamics to skew MOI distributions
  • 27. Future work: spatial models of Virophage—viruses of viruses Taylor et al, JTB (2014) Paired Entry Mode (PEM) Independent Entry Mode (IEM) Desnues et al. PNAS (2012) Fischer and Suttle Science (2011)
  • 28. Acknowledgements  Weitz Lab (GaTech)  Funding:  Quantitative Laws II  NSF Physics of Living Systems  James S Mcdonnell Foundation  Nerem Fellowship  Burroughs Wellcome Fund
  • 29. Acknowledgements Questions? Hosts E H I1 C Viruses 0 [1 5] [6 10] [11 15] [16 20] >20 BP Taylor, CJ Penington, JS W bioRxiv: 048876  Weitz Lab (GaTech)  Funding:  Quantitative Laws II  NSF Physics of Living Systems  James S Mcdonnell Foundation  Nerem Fellowship  Burroughs Wellcome Fund
  • 30.
  • 32. Parametrize based on prochlorococcus single time step System size: 500 x 500 lattice pts=¼ ml 32 Backup slide List processes