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

Table 2

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

Escape mutant	MV-H mutations	MV-F mutations	MV-M mutations	Shift
Normal Halle	No change	No change	No change	control
Halle-SLAM 1.1	I473M	M4V, S255G, N408S	No change	+
→ Halle-SLAM 1.2	D332G, T380I	No change	Y114H, I319T	+
Halle-SLAM 2.1	I25V, R62Q, V259G, V604A	D258G, D412G, L538G	No change	+
Halle-SLAM 2.2	D90G, M163T, F382S	I13M, I309K, C423R	R36G	+
→ Halle-SLAM 2.3	A158V	No change	M239I	+
Halle-SLAM 3	K13E	M4V, F116L, S229P, N380A	V80A, T95A	−
Halle-SLAM 4.1	L585P	I216V, K491R, A515T	F73L, Q310H	+
Halle-SLAM 4.2	L246S, Q311R	No change	Q310H	+
Halle-SLAM 4.3	M45L, I50F, K147E	No change	No change	−
Halle-SLAM 4.4	F382S	No change	Q310H	−
→ Halle-SLAM 5.1	No change	I329N	T172I	+
Halle-SLAM 5.2	No change	No change	V173I	−
Halle-SLAM 5.3	K364T, W472R	Q133R	K86R, T172I	+
Halle-SLAM 6	No change	T543K	No change	−
Halle-SLAM SSPE	H86R, R261G, R348G, D507G	S34P, I286V, Y440H, I511V	G245A	+
Halle-CD46 1.1	T93S, A182T, S244P	No change	No change	+
→ Halle-CD46 1.2	No change	M4I, V283A	No change	+
→ Halle-CD46 1.3	T177I, R533G	No change	I69T, I196V	+
Halle-CD46 1.4	H17R, K295E	No change	D290G	−
Halle-CD46 2.1	T469A	Y401H, R439G	L291I; Premature codon stop at R299	+
Halle-CD46 2.2	No change	L263S, K399R	R181S, L295P	+
Halle-CD46 2.3	K477R	N95S, R168G, N187D, Y417H	No change	+
Halle-CD46 2.4	Y410C	A124V, R154S, T214S	L178P, F317L	+
Halle-CD46 3.1	R22G, F180L	S2N, G40R, I90F, Q142R, Y254H, F332Y	I200M	−
Halle-CD46 3.2	N26I	F332Y	No change	−
→ Halle-CD46 3.3	L136P	No change	K243E, S312P	+
Halle-CD46 4.1	R556K	N525S	No change	−
Halle-CD46 4.2	S119A, I407V, S429L, V539A	L68P, I167T, I329V, Q359R	L280P, L291P, L294S, V303A	+
Halle-CD46 4.3	No change	No change	N136S, S257N	−
Halle-CD46 5.1	V317D, K375E	V428A, T545I	No change	+
Halle-CD46 5.2	Y66C, S73R	Q434L, E458G, K539E	Y5N	+
Halle-CD46 5.3	No change	No change	D39G, I260T	−
Halle-CD46 5.4	M288K, S409T	V86A, R102G, I470T,; L553P	No change	+
Halle-CD46 (6)	D135N, S169P	R51S, P319L, N331S	No change	+
Halle-CD46 SSPE 1	S48N, I50T, I55F, N262Y, L276F, S285G, I346V, H448R, K460R, E471A, A496T	R115G, L457W	R30G; Premature codon stop at R102	+
Halle-CD46 SSPE 2	N77S, M163T, G196D	S2T, A129V, M354T	L107P, Y232H, V303I	+
Halle-CD46 SSPE 3	Q391R	V74I, G256R, V318A, L457W, L507F	Q34R, E93G	+
Halle-CD46 SSPE 4	Q4L, L205Q, S532P, D574G	L457W	Q34R	+
Halle-CD46 SSPE 5	L95P, I118T, I427T I435T	L21H, V181A, S437G	Q34R	+
Halle-CD46 SSPE 1.1	E161G, M163T	I164V, A240V	P118S, V231A, I302V	+
Halle-CD46 SSPE 1.2	K13R, V80A, M163T	I164V, A240G, R535G	No change	+
Halle-CD46 SSPE 1.3	M163T, R195S, S244P, F382L, F571L	V39A, R102G, I164V, A240V	No change	+

CD46-dependant escape mutants were selected using Vero cells and SLAM-dependant escape mutants with CHO-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. The “Shift” column refers to flow cytometry studies made on the mutants. The Mean Fluorescence Intensity (MFI) values of the mutants were compared with that of Halle (non-mutated control). A plus sign in the “shift” column indicates those mutants having the capacity to induce a statistically important reduction (shift) in the MFI in interaction with any of the sera or specific anti-MV antibodies. Arrows indicate the six escape mutants with a minimal number of mutations that were selected for dissection studies. NB: for the Halle control, two selection steps to isolate Halle clones were made without sera. Three Halle clones were isolated and sequencing showed no mutations in their H, F, or M genes.