TABLE 1.

Parameter estimates of subgenomic HCV replication in Huh-7 cells^a

Rate constantb	Reaction definition	Kinetic rate constants (h−1)c:
		From the literature and simulations (half-life [h])	Based on sensitivity analyses (half-life [h])
k1	Tc formation	1-100† (molecule−1)	34-83‡
k2#	Nascent NS polyprotein translation	100*	100*
kc	Viral polyprotein cleavage	0.2-1†	0.4-0.8‡
kPin	RPcyt transport into VMS	0.2†	0.2†
kPout	RP transport into cytoplasm	0.2†	0.2†
kEin	Ecyt transport into VMS	4.0 × 10−6 to 4.0 × 10−5†	1.2 × 10−5 to 3.3 × 10−5‡
k3	RIp formation	0.001-0.02† (molecule−1)	0.01-0.02‡
k4p#	RP synthesis	1.7*	1.7*
k4m#	Rds synthesis	1.7*	1.7*
k5	RIds formation	k5/k3 = 200†	k5/k3 = 200†
μpcyt	RPcyt degradation	0.06-15.0*† (12-0.05)	2.9-11.3‡ (0.06-0.2)
μp	RP degradation	0.07* (10)	0.07* (10)
μds	Rds degradation	0.06* (12)	0.06* (12)
μIp	RIp degradation	0.01-0.06*† (17-12)	0.02-0.05‡
μIds	RIds degradation	μIds/kEin = 104†	μIds/kEin = 104†
μTc	Tc degradation	0.001-0.02† (700-35)	0.004-0.015‡ (46-173)
μE	E degradation	0.001-0.06† (700-12)	0.01-0.05‡ (14-70)
μEcyt	Ecyt degradation	0.06* (12)	0.06* (12)

^aAbbreviations: T_c, translation complex, which is composed of plus-strand RNA and 10 ribosomes; R_P^cyt, plus-strand RNA in cytoplasm; R_P and R_ds, free plus-strand RNA and dsRNA in VMS; R_Ip and R_Ids, replicative intermediate complexes (NS5B polymerase and template RNA), where the R_P and R_ds, respectively, serve as templates; E, NS5B polymerase in VMS; E^cyt, NS5B polymerase in cytoplasm; NS, nonstructural.

^b#, We assume that once the translation or synthesis processes are done, the T_c, R_Ip, and R_Ids complexes dissociate immediately.

^c*, Obtained from the literature as explained in Materials and Methods; †, obtained from simulation as explained in Results; ‡, obtained from sensitivity analysis as explained in Results. Half-life values are indicated in parentheses.