Sim2Virus User's Manual


Sim2Virus is a Java applet that models the competitive spread of two types of virus on a hexagonal grid of cells. Infected cells are colored red or green according to the type of virus, with uninfected cells remaining white. In the case that simultaneous infection of a cell by both types of virus is allowed (superinfection), an intermediate color is used, with the median value being displayed as yellow. When a cell dies it retains its final color.

Initial infection:

The intial infection occurs in areas called the foci, one for each type of virus. The default is that both foci are in the center of the screen and are the same shape, so they overlap exactly, and that both infections start simultaneouly. If a nonzero value is entered for the DeltaX parameter the green focus is moved to the left by that number of cells and the red focus is moved to the right by the same distance. If a nonzero value is entered for the DeltaT parameter the red infection starts later by that number of time steps. The user can also specify the radius of each focus and select from one of four possible shapes:

The number of viruses of each type in the initial infection is controlled by the MOI parameters. The MOI specifies how many of each type of virus is placed on the focus. The number of cells in the focus is multiplied by the MOI, and this quantity of virus as spread uniformly at random across the focus. Any cell that gets a receptor in the first time step will become infected with the viruses on that cell. Receptors are assigned at random at a rate given by the "% infectible" field.

The user can also turn on a thin black line delineating the border of the focal area. This is purely a visual aid - it has no effect on the simulation.

Cell life cycle:

The following diagram illustrates the life-cycle of a cell:

State diagram giving cell life-cycle

The six states labelled "infected" represent the fact that a cell lives for at most six time steps before it dies. This is controlled by a timer that is set to a random value of 4, 5, or 6 when the cell first becomes infected. Viruses bud out of infected cells only from the second and fourth (and possibly sixth) of these states.

State transitions:

normal to infectible
This transition models a cell acquiring a receptor. At each step (including the initialization step), a fraction of cells given by the "% infectible" parameter acquires a receptor. For each cell that acquires a receptor, a timer is set to a uniform random value ranging from "Min RRT" through "Max RRT" (Receptor Retention Time).
infectible to normal
If the above timer expires before the cell becomes infected it returns to normal
infectible to infected
This transition models a cell becoming infected when virus is present at the same time the cell has a receptor. This can happen in the same time step as the cell acquires the receptor (normal to infectible transition). At this point, the cell's timer is set to a uniform random value between 4 and 6 inclusive. See "Virus lifetime" (below) for an explanation of how viruses enter a cell.
infected to infected
The "infected" state is made up of six substates. The number of states traversed is determined by the setting of the cell's timer when it enters the first "infected" state. Viruses bud out from the cell to the six adjacent cells at the second, fourth, and (if the timer was set to six) sixth states. When budding occurs, an average of about 100 viruses are distributed randomly to the six adjacent cells. If the adjacent cell is already infected and superinfection is allowed the viruses enter the cell directly, otherwise they wait on the surface of the cell. If the budding cell was infected by both types of virus they are distributed in proportion to the ratio in that cell.
infected to deceased
A cell remains infected for between 4 and 6 time steps, after which it dies.

Virus lifetime:

The length of time a virus can live outside a cell is controlled by the "Max age" parameter. Allowable values are from one to four time steps. When a cell becomes infectible, the number of live viruses on the surface of the cell is calculated. If superinfection is not allowed, the cell becomes infected by the virus that is in the majority. If superinfection is allowed, viruses enter the cell in proportion to the ratio on the surface, however there is also a probability that the cell becomes infected with one type of virus. This probability increases linearly from 0 (if the two types of virus occur in equal numbers) to 1 (if only one type of virus is present).

Applet controls:

The layour of the applet looks like this:

Screen shot of the applet

The "MOI" fields allow the user to specify (on average) how many viruses of each type are placed on cells in the focus initially
Max age (choice menus)
The number of time steps a virus can live outside a cell
Focus shape (choice menu)
The shape of the area where the initial viruses are deposited (see "Initial infection, above)
Focus radius
The value in this field specifies the size of each focal area
Superinfection (radio buttons)
If superinfection is allowed a cell can become infected by both types of virus simultaneously
Green only
Show only the green viruses. This affects only the display - the red viruses are still present in the simulation
Red + Green
Show both types of virus
Red only
Show only the red viruses. This affects only the display - the green viruses are still present in the simulation
Border on/off
Displays or hides a thin black outline around the focus
Restart the simulation with a new initial infection
Continue simulating the current infection
The center of the green focus will be moved left by this number of cells, while the center of the red focus will be moved right by the same number.
The time step when the initial infection for the red virus should start. The initial infection for the green virus always starts at time 0.
% infectible
The proportion of cells becoming infectible (acquiring a receptor) at each time step
Minimum Receptor Retention Time, the minimum number of time steps that a cell remains infectible
Maximum Receptor Retention Time, the maximum number of time steps that a cell remains infectible
The number in this field specifies how many time steps are simulated with each click of the "Run" button

Statistics window:

This window displays statistics of the numbers of cells with different ratios of red and green viruses.

The leftmost column is the time and the next column is the number of cells that are all green. The rightmost column is the number of cells that are all red. The remaining columns are ten percentile counts for cells that have a mix of red and green.

A view of the statistics window after 30 time steps have been simulated: Statistics window