Evidence for Strain-Specific SSPE Risk
Yes, there is compelling molecular evidence that certain wild measles virus strains are more prone to causing SSPE, specifically those containing the PEA motif (P64, E89, A209) in their M protein, which is present in 9 of 10 sequenced wild-type genotypes but notably absent in vaccine strains and genotype B3—a genotype that has never been reported to cause SSPE. 1
Molecular Markers Distinguishing SSPE-Prone Strains
The most significant finding comes from comparative analysis of the matrix (M) protein primary sequence:
Wild-type measles viruses that cause SSPE consistently have the PEA motif (proline at position 64, glutamic acid at 89, and alanine at 209) in their M protein, while vaccine strains like Moraten have SKT (serine-lysine-threonine) or PKT motifs instead 1
The alanine at position 209 (A209) appears particularly critical for increased viral spread, as demonstrated through recombinant measles virus experiments that linked this specific residue to enhanced transmission capacity 1
Genotype B3 is the only wild-type genotype (among 10 sequenced) that lacks the complete PEA motif, having PET instead, and notably no SSPE cases caused by genotype B3 have been reported, providing strong correlative evidence for the PEA motif as a molecular risk marker 1
Strain-Specific Observations from Outbreaks
Epidemiological data supports strain-specific SSPE risk:
The D6 genotype was definitively identified in brain tissue from three Argentine children who developed SSPE 4 years after contracting measles during the 1998 outbreak, with phylogenetic analysis confirming these were wild-type D6 strains, not vaccine strains 2
All documented SSPE cases are caused by wild-type measles virus, never by vaccine strains, despite billions of vaccine doses administered globally 3, 4
Mechanistic Basis for Strain Differences
The structural differences explain why certain strains persist in neural tissue:
SSPE-associated viruses demonstrate clustered mutations particularly in the M gene that destroy normal protein structure and function, preventing formation of complete infectious virus particles 5
Mutations in the F protein of SSPE viruses confer hyperfusogenic properties that facilitate transneuronal spread, allowing cell-to-cell transmission without requiring extracellular budding 5
Non-budding, cell-associated SSPE strains lack detectable M protein, which is essential for this phenotype and appears critical for establishing persistent CNS infection 6
Clinical Implications
When evaluating SSPE risk:
The PEA motif in wild-type strains represents a molecular marker for SSPE risk, though routine genotyping of circulating measles strains for this marker is not yet standard practice 1
Measles vaccination remains the only proven prevention strategy regardless of circulating strain, as vaccine strains uniformly lack the PEA motif and have never caused SSPE 3, 4
SSPE incidence correlates directly with measles incidence in a population, so any wild-type measles infection carries risk, but strains with the PEA motif appear biologically predisposed to CNS persistence 7, 5
Important Caveats
While the PEA motif is strongly associated with SSPE, not every infection with a PEA-containing strain causes SSPE—the disease remains rare (estimated 4-11 per 100,000 measles cases) even with high-risk strains 5
The mutations that ultimately cause SSPE develop during persistent infection in the brain, so the initial infecting wild-type virus undergoes further adaptation after CNS invasion 5, 6