SSPE-Prone Measles Virus Characteristics
Yes, a measles virus is considered SSPE-prone when it possesses specific viral mutations that enhance fusion activity and enable persistent, cell-to-cell spread within the central nervous system without triggering strong cytopathology. 1, 2
Key Viral Traits That Define SSPE-Prone Measles Virus
Hyperfusogenic Fusion (F) Protein Mutations
The hallmark of SSPE-causing measles viruses is the presence of fusion-enhancing substitutions in the F protein (such as T461I, N465I, S103I/N462S/N465S) that destabilize the prefusion conformation of the F protein trimer, thereby dramatically increasing fusion activity 1, 2
These mutations enable the virus to spread efficiently in human neuronal cells through direct cell-to-cell fusion without requiring the typical measles virus receptors (SLAM or nectin 4) that neurons lack 2
The N465I mutation alone is sufficient to confer a hyperfusogenic phenotype and shift viral tropism from lymphoid tissue to neural tissue 1
Hypermutated Matrix (M) Gene
SSPE-causing measles viruses characteristically display a hypermutated M gene, which is a consistent finding across multiple SSPE cases 1, 3
These mutations in the M protein facilitate immune evasion and contribute to viral persistence within the CNS 3
Cell-to-Cell Spread Without Cytopathology
The critical functional property is that these hyperfusogenic viruses spread extensively in neuronal cells without inducing syncytia formation or strong cytopathic effects, allowing persistent infection rather than acute cell death 2
This contrasts sharply with their behavior in SLAM- or nectin 4-expressing peripheral cells, where the same mutations cause excessive cytopathology and reduced viral titers 2
Clinical Implications of These Viral Traits
Tissue-Specific Pathogenicity
Enhanced fusion activity is beneficial for measles virus spread specifically in the CNS where minimal cytopathology occurs, but detrimental in peripheral tissues due to excessive cell damage 2
Recombinant wild-type measles virus engineered with SSPE-derived F genes loses lymphotropism but gains the ability to disseminate efficiently in neural cultures 1
Diagnostic Relevance
Detection of measles virus RNA with these characteristic mutations (hypermutated M gene and F protein mutations) in brain tissue or CSF supports the diagnosis of SSPE 1
CSF analysis showing elevated antimeasles antibodies combined with detection of viral RNA confirms persistent infection 4, 3
Important Caveats
Not all measles infections lead to SSPE—only approximately 4-11 per 100,000 measles-infected individuals develop this complication, suggesting additional host factors beyond viral traits contribute to disease development 5
The mutations that render measles virus SSPE-prone appear to arise during persistent infection rather than being present in the initial infecting virus, representing viral adaptation to the CNS environment 3, 2
Measles vaccination prevents SSPE entirely by preventing measles infection—the vaccine virus does not possess these SSPE-prone characteristics and does not increase SSPE risk 6, 7