TABLE 3     Variables and parameter(s) used in simulation corresponding to experimental measurements and conditions.

Experiment Reference / Simulation Result	Measurements in Experiment / Variables in Simulation	Conditions in Experiment / Parameter(s) in Simulation
Fig. 3 B in (18)	Protein level of A3G	Vector Vif:APO-3G (μg:μg) = 4:2, 1:2, 0.25:2, 0:2
Fig. 2 A in this work	Normalized  at 24h	= 4, 1, 0.25, 0.
Fig. 1 B in (19)	Relative amount of A3G packaged into virions at 48h post-infection	Vector HA-A3G:pNL4-3ΔVif (μg:μg) = 0:60, 1:60, 2:60, 5:60, 10:60, 20:60
Fig. 2 B in this work	at 48h simulation time	= 0, 0.5, 1, 2.5, 5, 10.  = 0
Fig. 2 B in (20)	Percentage of packaged A3G in total A3G at 24h post-infection	1.  Constant pNL4-3 (expressing constant amounts of Vif) = 2.5μg, varying pcDNA-APO3G. = 0, 0.5, or 2.5μg, total DNA was adjusted to 5μg. 2.  Constant Vif-defective pNL4-3Vif(-) = 2.5μg, varying Vif expression vector pNL-A1 = 0, 0.5, or 2μg, total DNA was adjusted to 6μg.
Fig. 2 C in this work	at 24h simulation time	,
Fig. 4 A in (21)	Relative viral infectivity in subsequent infection	WT and ΔVif provirus 3μg and A3G = 0, 0.01, 0.02, 0.05, 0.1 or 0.2μg adjusted with an empty vector to 4μg total.
Fig. 2 D in this work	at 48h simulation time	or 0 (for ΔVif), =0, 0.1, 0.2, 0.5, 1 or 2

Shaded row denotes the experiments; the row directly below represents the corresponding simulations.

FIGURE LEGENDS

Figure Legends

 

FIGURE 1

Schematic of cellular APO and viral Vif related virus production.  Viral RNA is transcribed from provirus integrated in cellular genome and yields viral proteins Tat, Gag and Vif.  Tat transactivates viral transcription to accelerate viral RNA synthesis.  Gag is a polyprotein used to form the main virus structure.  Regulatory protein Vif acts as anti cell defense factor to form complex with cellular cytidine deaminase enzyme APO and promote its degradation through ubiquitination.  Both Vif and APO are able to be incorporated into nascent formed virion.

 

FIGURE 2

Comparison between experiments and simulations.  (A) Viral Vif downmodulates cellular protein APO.  Note the direction of horizontal axis is reversed.  (B) Overexpressing APO increase the relative ratio of packaged APO into virions.  (C) 2D plot of the percentage of packaged APO in total APO, by varying transcription rate of APO RNA and rate of Vif expressing.  (D) Negative correlation between viral infectivity and simulated .  Note the vertical axis direction of  is reversed.  See text and Table 3 for details.

 

FIGURE 3

Parameter sensitivity analysis.  Vertical axis denotes relative parameter sensitivity value on the steady state value of variable ,  and accumulated number for  at 48h post-infection.  The locations of bars are in descending order from left to right for sensitivity on variable .  The value bars are grouped by each parameter.  Note the sensitivity values on variables   and  are scaled down for plot convenience.

 

FIGURE 4

Perturbation analysis.  Each parameter was varied by 4 magnitude to explore its influence on the steady state value of variable ,  and the accumulated value of  at 48h post-infection.  Values on variables  and  are scaled down as legend indicated.  (A) Gag related parameter  and .  (B) Tat related parameter ,  and .

 

FIGURE 1  

FIGURE 2  

 

FIGURE 3

FIGURE 4