Mutations in the H, F, or M Proteins Can Facilitate Resistance of Measles Virus to Neutralizing Human Anti-MV Sera

Table 1

Mutations present in the H, F, and M genes of MV-G954 escape mutants obtained by in vitro immune selection.

Escape mutant	MV-H mutations	MV-F mutations	MV-M mutations
G-954 without serum	No change	No change	No change
G-954 + serum 1 clone 1	I32V, F111L, I219M	G26S, V107I, H141R, V178A, S285G, Q359P, E481G	K92E, Y114C, S133G, N168D, V192M, F217L
G-954 + serum 1 clone 2	K185E, M222T, V322A, D442N, V525A	N380D	V37A, N168D, P314L
G-954 + serum 2 clone 1	D135G, Y252H, Q334R, C381R	I232V, N392S, E481G	S17P, I319T
G-954 + serum 2 clone 2	No change	P227S, R301L, V550A	S17P
G-954 + serum 2 clone 3	S335P	M15I	S17P
G-954 + serum 3 clone 1	R62W, V91A, S340P, G356S, E379G, M602V	P103S, I298V, G376R	S17P, F50S, L122H, F276L
G-954 + serum 3 clone 2	W336R, G591S	No change	S17P
G-954 + serum 3 clone 3	N200S, L470S	Q182R, R439W	R86K, N136S, E89K,V183A, R225G
G-954 + serum 4	T370A, L454P, T595A	N186Y, V322A, D461G	S17P, M51V, M53V, L90F, R297G
G-954 + serum 5 clone 1	M333V, E422G	L68P, S197P, I418T	Premature termination codon at amino acid W12
G-954 + serum 5 clone 2	N26S, D404G, E611G. There are three additional  amino  acids: QGC	I36V	S17P, F54L, E96G
G-954 + serum 6	H495Y	F14L, M49T, G467E	S17P, N208D, premature termination codon at amino acid K238
G-954 + SSPE serum clone 1	I50V, H61R, D128N, Y232H, D283N	M15K, A96T, V283A	S17P
G-954 + SSPE serum clone 2	V485A	No change	S17P

Escape mutants were selected using Vero-SLAM cells and their H, F, and M genes were then sequenced. The numbers 1–6 refer to the different sera from healthy MV-vaccinated donors used for selection; SSPE refers to the SSPE serum. Escape mutant mutations also found in SSPE cases are in bold. NB: for the G-954 control, two selection steps to isolate G-954 clones were made without sera. Three G-954 clones were isolated and sequencing showed no mutations in their H, F, or M genes. Strikingly, 12 of the 14 escape mutants (86%) contain at least one “SSPE mutation”; that is, a mutation that has also been found in an SSPE case. 42% of the H proteins, 57% of the M proteins, and 36% of the F proteins from the escape mutants contain at least one “SSPE mutation.”