Table 3.

Identification of amino acid changes in the VACV DNA polymerase following selective pressure with the ANPs HPMPC, HPMPDAP, and HPMPO-DAPy starting from four plaque-purified clones, denoted VV1, VV2, VV8, and VV11, isolated from the parental VACV Lederle strain.

A. VACV Mutants Selected under Pressure of HPMPC (Cidofovir).
Virus	Clone	Amino Acid Changes in Viral DNA Polymerase
		Known Natural Occurring Genetic Polymorphisms	Known Drug-Resistant Mutations (Dark Blue) and Novel Mutations (Yellow)
VV1	clone 3	R97H, T845M, G857R, 936–938 NΔG	—			A314T	—		—	A684V
VV2	clone 2	W8C, 936–938 ANV	M313I			—	R577G		A677T	A684V
VV8	clone 1	R246Q, G857R, 936–938 ANV	—			A314V	L510S		—	A684V
VV11	clone 1	L90S, R235L, T845M, G857R, S898T, 936–938 NΔG	—			A314T	—		M656I	A684V
B. VACV Mutants Selected under Pressure of HPMPDAP.
Virus	Clone	Amino Acid Changes in Viral DNA Polymerase
		Known Natural Occurring Genetic Polymorphisms	Known Drug-Resistant Mutations (Dark Blue) and Novel Mutations (Yellow)
VV1	clone 1	R23G, L420S, T845M, G857R, 936–938 NΔG	A314V			—	T500I	—		T688A	—
VV2	clone 3	T71I, T845M, G857R, 936–938 NΔG	—			D480Y	—	A684V		—	A705T
VV8	clone 1	R246Q, T845M, G857R, 936–938 NΔG	A314T			—	—	A684V		—	—
VV11	clone 1	I68T, L420S, T845M, G857R, C865S, 936–938 NΔG	A314T			—	—	A684V		—	L696S
C. VACV Mutants Selected under Pressure of HPMPO-DAPy.
Virus	Clone	Amino Acid Changes in Viral DNA Polymerase
		Known Natural Occurring Genetic Polymorphisms	Known Drug-Resistant Mutations (Dark Blue) and Novel Mutations (Yellow)
VV1	clone 3	T845M, G857R, 936–938 NΔG	—	—	—	—	—	—	A632T	—	S851Y
VV2	clone 3	T845M, G857R, 936–938 NΔG	R155S	M313I	-	R407C	L511F	—	—	A684V	—
VV8	clone 1	R246Q, T845M, G857R, 936–938 NΔG	—	M313I	—	—	—	A613T	—	A684V	—
VV11	clone 1	T845M, G857R, 936–938 NΔG	G138E	—	A314T	—	—	—	—	—	—