Does Subacute Sclerosing Panencephalitis (SSPE) result from a pre-existing defective or mutated measles virus?

Does SSPE Result from a Defective or Mutated Measles Virus?

Yes, SSPE is caused by persistent infection with defective, mutated strains of measles virus that develop after the initial wild-type measles infection. 1, 2

Viral Pathogenesis

The measles virus that causes SSPE undergoes specific mutations during persistent infection in the central nervous system:

• Defective interfering (DI) particles with 5' copy-back RNA structures have been identified in SSPE brain tissue, representing mutant measles genomes that lack normal replication capacity 3
• These defective viral genomes encode dysfunctional viral envelope proteins, which allows the virus to persist intracellularly while evading immune clearance 3
• The mutations are not present in the original infecting virus but develop during the prolonged persistence phase, typically years after the initial measles infection 4, 5

Clinical Timeline and Mechanism

SSPE develops through a specific sequence:

• Initial infection occurs with wild-type measles virus, often in very young children (under 2 years of age carries higher risk) 2
• A latency period of 4-15 years follows the acute measles infection 2
• During this time, the virus persists in the CNS and accumulates mutations that create defective viral particles 3
• The defective virus can replicate but cannot produce infectious virions, leading to cell-to-cell spread without extracellular release 4, 3

Key Distinguishing Features

SSPE is NOT caused by:

• Pre-existing defective virus at the time of initial infection 3
• Measles vaccine virus (vaccination actually prevents SSPE) 1, 6
• A different strain of measles—it's the same virus that has mutated over time 4, 5

The defective nature includes:

• Multiple discrete defective RNA species coexisting in each SSPE brain 3
• Minimum DI stem length of 95 nucleotides affecting replication/encapsidation functions 3
• Loss of selective pressure compared to acute infections, allowing numerous defective particles to persist 3

Clinical Implications

The defective viral nature explains SSPE's characteristic presentation:

• Insidious onset with personality changes and declining intellectual performance progressing to seizures, myoclonic jerks, and death 7, 1
• EEG shows periodic complexes with 1:1 relationship to myoclonic jerks 7, 1
• CSF antibody detection is diagnostic, showing intrathecal synthesis of measles-specific antibodies 1, 2
• Immune dysregulation with elevated lymphocyte subsets and immunoglobulin levels (particularly IgG, IgM, IgE) 8

Prevention Context

Understanding the mutational origin is critical for prevention:

• Vaccination prevents SSPE by preventing the initial wild-type measles infection that would later mutate 1, 6
• Unvaccinated children who contract measles, especially before age 2, face the highest SSPE risk 2
• Countries with high measles vaccination coverage have near-elimination of SSPE cases 1, 6