Table 2.

Studies on mouse adaptation.

Mouse Adaptation Mutation	Adapted Strain	Adaptation Procedure	Replication in Cell Lines	Virulence in an Animal Model	References
VP2-K149M	MP4	Four passages in 1-day-old ICR mice	MP4 is highly proliferative in several human cell lines	VP2-K149M and VP1-Q145E are together responsible for mouse virulence	[31,33]
VP2-K149I	CHO-26M MP-26M	Six passages in a hamster cell line (CHO), then f our passages in suckling mice	NT	VP2-K149I did not contribute much, and VP1-G145E was the most critical mutation	[30]
VP2-K149I VP2-K149M	1095-LPS1 SK-EV006-LPS1 C7/Osaka-LPS1 75-Yamagata-LPS1	One passage in a human PSGL1 overexpressing mouse cell line (L-PSGL1)	Adaptation increased proliferation in L-PSGL1	NT	[56]
VP2-K149I VP2-K149M	CHO-B5 CHO-C2	Four to eight passages in a hamster cell line (CHO)	CHO-B5, CHO-C4, and the parental strains containing VP2-K149I or VP2-K149M showed enhanced proliferation in CHO cells. All of these viruses are VP1-145Q (HS-binding)	NT	[48]
VP2-K149I	EV71:TLLm EV71:TLLmv	60 and 100 passages in a mouse cell line (NIH/3T3)	TLLm and TLLmv show increased efficiency for infecting various rodent cell lines, but the VP2-K149I point mutant does not show the same increase in infection in such cells. The reason for this may be that the strains used are HS-nonbinding	No increase in virulence was observed with VP2-K149I	[57,58]
VP2-K149I	GZ-CII	VP2-149I have been isolated from a human patient	NT	GZ-CII and artificially mutated VP2-K149I viruses are highly virulent in mice	[55]

NT: not tested.