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Altered ratios of measles virus transcripts in diseased human brains
R Cattaneo1, G Rebmann, K Baczko
1Institut für Molekularbiologie I, Universität Zürich, Hönggerberg, Switzerland.
Abstract:
In rare cases measles virus (MV) induces subacute sclerosing panencephalitis (SSPE) or measles inclusion body encephalitis (MIBE), two lethal diseases of the human central nervous system. MV transcripts present in the brains of two SSPE patients and one MIBE patient were analyzed by quantitative Northern blots. In all three cases the transcripts from the first MV gene were relatively abundant, amounting to about one-tenth of that in lytically infected cells. However, the quantity of transcripts decreased sharply for each subsequent MV gene, arriving at 200-fold lower levels for the fifth MV gene. In comparison gradients of transcript levels are more shallow in either lytically or persistently infected cultured cells, where the transcripts of the fifth MV gene are only about five times less abundant than those of the first. These altered ratios of mRNAs appear to be typical for persistent MV brain infections and most likely lead to reduced expression of the viral envelope proteins, encoded by distal MV genes, at the surface of brain cells. This could account for the lack of viral budding and allow persistent MV infections to elude immune surveillance.
Insights
Measles virus (MV) brain infections show significantly reduced transcript levels for later genes, unlike cultured cells. This pattern may explain how persistent MV infections evade immune detection.
Area of Science:
- Neurovirology
- Molecular Biology
Background:
- Measles virus (MV) can cause lethal human central nervous system diseases: subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE).
- Understanding MV gene expression in the brain is crucial for elucidating disease pathogenesis.
Observation:
- Quantitative Northern blot analysis was performed on MV transcripts from the brains of two SSPE and one MIBE patient.
- A steep decline in transcript quantity was observed for successive MV genes, with the fifth gene showing 200-fold lower levels compared to the first.
Findings:
- Transcript gradients in patient brains were significantly steeper than in lytically or persistently infected cultured cells.
- Cultured cells showed only a five-fold decrease in transcripts for the fifth MV gene compared to the first.
Implications:
- Altered mRNA ratios in persistent MV brain infections likely reduce viral envelope protein expression on brain cells.
- This reduced expression may inhibit viral budding and facilitate immune evasion by persistent MV infections.