Is Subacute Sclerosing Panencephalitis (SSPE) a latent infection or a chronic, ongoing intracellular Central Nervous System (CNS) infection with continuous low-level viral antigen expression causing continuous immune stimulation?

SSPE: Chronic Ongoing CNS Infection, Not Classic Latency

Yes, this statement is correct—SSPE represents a chronic, ongoing intracellular CNS infection with continuous low-level viral antigen expression and continuous immune stimulation, rather than a true latent infection in the classic sense. 1, 2

Key Pathophysiologic Distinction

The critical difference lies in the persistent active viral replication occurring in SSPE:

• Measles-specific IgM remains persistently elevated for years—even decades—in SSPE patients, which is pathognomonic for ongoing CNS viral replication rather than dormant latency 1, 2
• In contrast, acute measles infection shows IgM that becomes detectable 1-2 days after rash onset, peaks at 7-10 days, and becomes completely undetectable within 30-60 days 2, 3
• The persistent IgM in SSPE reflects active viral persistence with ongoing immune stimulation from CNS viral replication, not systemic viremia 2

Evidence of Continuous Viral Activity

Multiple diagnostic markers confirm ongoing viral activity rather than dormancy:

• Detection of measles-specific IgM in both serum and CSF (often higher in CSF than serum) indicates continuous intrathecal antibody production 1, 2
• CSF/serum measles antibody index ≥1.5 confirms intrathecal synthesis with 100% sensitivity and 93.3% specificity, demonstrating local CNS production rather than passive antibody leakage 1, 2
• The virus establishes true persistent infection in neurons, spreading trans-synaptically, with envelope proteins accumulating mutations that facilitate neuronal spread 2, 4

Clinical Timeline Demonstrates Active Disease

The disease progression contradicts classic latency:

• Initial measles infection occurs with viremia during acute illness 2
• A period of 2-10 years (average 6 years) follows with no systemic viremia but ongoing CNS infection 2, 5, 6
• SSPE then emerges with insidious neurological symptoms reflecting continuous CNS viral replication and immune-mediated damage 1, 3, 5

Molecular Mechanisms Supporting Ongoing Infection

Research demonstrates continuous viral activity:

• Hyperfusogenic mutations in the measles fusion protein (T461I and S103I/N462S/N465S) found in SSPE isolates promote efficient spread in neuronal cells without causing syncytia formation 4
• These mutations destabilize the prefusion conformation of the F protein, enhancing fusion activity specifically beneficial for neuronal spread 4
• The virus spreads efficiently in neurons where no cytopathology occurs, allowing persistent infection rather than cell death 4

Common Pitfall: Confusing with True Latency

Do not confuse SSPE with classic latent infections (like HSV or VZV latency):

• True latency involves no viral replication, no viral antigen expression, and no immune stimulation during the dormant period
• SSPE involves continuous low-level viral replication with persistent antigen expression driving ongoing immune responses 1, 2
• The presence of persistent IgM for years is incompatible with true latency and indicates active viral persistence 2

Clinical Implications

This distinction has important diagnostic and conceptual implications:

• SSPE is progressive and almost always fatal, with continuous CNS damage from ongoing infection and immune-mediated injury 1, 6
• Treatment goals focus on controlling seizures and myoclonus while providing supportive care, as the continuous viral activity makes cure extremely difficult 1, 5
• The only effective prevention is measles vaccination with two doses of MMR vaccine, which has essentially eliminated SSPE in highly vaccinated populations 1, 3