SSPE and Measles Virus Strain Predisposition
SSPE is caused by wild-type measles virus strains with specific molecular characteristics, particularly mutations in the M protein that distinguish them from vaccine strains, though any wild-type measles infection carries risk—the critical factor is exposure to wild-type measles, not a predetermined "SSPE strain." 1
Viral Strain Characteristics in SSPE
Wild-Type vs. Vaccine Strain Distinction
- All documented SSPE cases result from wild-type measles virus, never from vaccine strains, which is a fundamental epidemiological observation across all reported cases 2, 3
- The molecular basis for this distinction lies in the M protein structure: wild-type strains causing SSPE possess a specific PEA motif (P64, E89, A209), while vaccine strains like Moraten have SKT (S64, K89, T209) or PKT motifs 1
- The A209 residue in particular appears linked to increased viral spread capacity, which may facilitate the persistent CNS infection characteristic of SSPE 1
Genotype Distribution and Risk
- Of the 10 wild-type measles genotypes with sequenced M proteins, 9 possess the PEA motif, with genotype B3 being the exception (having PET instead) 1
- Notably, no SSPE cases caused by genotype B3 have been reported, suggesting the PEA motif serves as a molecular marker for SSPE risk 1
- However, this does not mean certain strains are "predisposed" to cause SSPE—rather, approximately 4-11 per 100,000 individuals infected with any wild-type measles develop SSPE, indicating host factors and viral persistence mechanisms are equally critical 3, 4
Viral Mutations During Persistence
SSPE-Specific Mutations
- SSPE-causing measles viruses are characterized by hypermutated genomes, particularly in the M gene, which develop during persistent CNS infection 5
- Additional mutations in the F gene (such as N465I) create a hyperfusogenic phenotype that facilitates rapid spread throughout neural tissue rather than lymphoid tissue 5
- These mutations represent adaptations that occur after initial infection during the years of CNS persistence, not pre-existing strain characteristics 5
Defective Viral Strains
- SSPE results from persistent infection with defective measles virus strains that have accumulated mutations over years of CNS persistence 6
- The virus detected in SSPE brains shows loss of normal lymphotropism and instead efficiently disseminates in neural cultures 5
Clinical Implications
The Primary Risk Factor is Exposure, Not Strain Type
- The dominant risk factor for SSPE is lack of measles vaccination and subsequent wild-type measles infection, particularly at young ages (under 2 years) 3, 4, 6
- Three unvaccinated patients who developed SSPE had measles infections at 3,8, and 30 months of age, with SSPE developing 15,6, and 4.5 years later respectively 6
- Measles vaccination is the only effective prevention strategy, having essentially eliminated SSPE in highly vaccinated populations 2, 3, 7
Important Caveats
- When rare SSPE cases have been reported in vaccinated children, evidence indicates these children likely had unrecognized wild-type measles infection before vaccination, and SSPE resulted from that natural infection, not the vaccine 2, 3
- Immunocompromised states (HIV, leukemia, lymphoma) increase susceptibility to both measles and subsequent SSPE development 3
- The disease develops from persistent CNS infection years after the initial measles infection when systemic viremia has long resolved, not from ongoing high viremia 4