Table 4.

Variant positions, common to more than one population and having a rate >5% in passage 120

Protein	AA position	AA change	Number of population samples	Virus variants	Passage 1 average rate	Passage 60 average rate	Passage 120 average rate
VP3	234	Q > E	2	WT	0.0024	0.4682	0.6749
3D	372	A > V	3	WT	0.0010	0.0256	0.3701
VP2	137	L > P	2	372	0.0005	0.0959	0.3317
VP3	204	A > V	8	WT 372 299	0.0006	0.0462	0.2560
3A	51	T > A	3	299	0.0013	0.0125	0.2477
VP2	138	D > N	4	WT 299	0.0003	0.0116	0.2206
3B	6	V > L	5	WT 372	0.0001	0.0113	0.1498
VP4	21	N > D	4	WT 372	0.0003	0.0310	0.1493
VP4	17	N > D	6	WT 372 299	0.0011	0.0088	0.1219
VP4	15	R > G	4	372 299	0.0011	0.0036	0.0760
3D	299	S > T	2	WT 372	0.0004	0.0058	0.0626

Seven variants were within viral capsid proteins, two in 3D, one in 3A and one in 3B. The 3D mutations are the known natural fidelity variants of the polymerase: S299T, known to decrease viral replication fidelity, and A372V, known to increase viral replication fidelity. By passage 120, the S299T variant, accumulated to 5% and 1% of the A372V and WT populations respectively. A372V accumulated in all three WT populations with an average rate of 37% at passage 120. These observations suggest that viral populations may fine tune their mutation rates during their infection cycles by generating mixed populations of fidelity variants, so as to increase adaptability (fidelity decrease) while maintaining genetic integrity (fidelity increase).