TABLE 2.

Multiple polymerase mutants found within treated individuals

Woodchucka	Treatment	WHV variant (no. of clones)b	Previous report
326	14 mo on, 4 mo off	V (5)c/wt (1)	ND
	14 mo on, 5 mo off	V (8)/wt (3)	ND
331	12 mo	IV (7)/I (3)	ND
	14 mo	I (7)/IV (3)d/II (1)d, VII (1), XI (1)	I/?
	14 mo on, 2 mo off	I (8)/V (3)/II (1), IV (1), VII (1)e	ND
	14 mo on, 5 mo off	V (6)/I (4)/II (1), IX (1), XI (1)	ND
335	12 mo	I (9)/IV (2)/V (1)	wt/I
	14 mo on, 1 mo off	IV (4), wt (4)f/I (2)/II (1), IX (1)g	ND
	14 mo on, 4 mo off	I (5), IV (5)/wt (2)/II (1)	ND
	14 mo on, 5 mo off	I (6)/IV (3)/wt (1), VII (1)h	ND
336	14 mo on, 1 mo off	II (10), VI (3)/I (1), VII (1)	ND
	14 mo on, 5 mo off	II (5)/VII (2), X (2)/III (1)	ND
337	12 mo	I (10)/VI (2)/wt (1), II (1), VII (1)	wt/I, II
	14 mo	I (10)/II (5)/VII (3)/VI (1)	ND
338	14 mo on, 5 mo off	I (6)/V (3) /wt (2)	ND
342	14 mo on, 5 mo off	I (7)/wt (6)	ND

^aWoodchucks were treated with lamivudine for ca 14 months (27), after which, lamivudine therapy was withdrawn (29). The nucleotide sequences of PCR products corresponding to nt 500 to 1050 of the WHV genome were determined. Aside from the identified mutations, individual clones contained less than 3 nt changes per 500 nt (on average, 0.105%). These mutations were thought to be spontaneous mutations or misamplification by Taq polymerase.

^bThe active site of the pol gene was amplified from serum virus by PCR. The products were then cloned and sequenced. wt, wild type.

^cType V produces an A566S amino acid change. One of the type V mutant clones also had a V471I amino acid change in the pol gene.

^dAn F551L amino acid change in the pol gene was found in one of the type IV mutant clones and in the type II mutant clone.

^eAn M635L amino acid change in the pol gene was found in the type VII clone.

^fOne of the wild-type clones had an A566S amino acid change in the pol gene.

^gAn M635L amino acid change in the pol gene was found in the type IX clone.

^hAn M635L amino acid change in the pol gene was found in the type VII clone.