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Measles virus gene expression in lytic and persistent infections of a human lymphoblastoid cell line
1Unidad de Virología, Hospital Ramón y Cajal, Madrid, Spain.
Abstract:
MOMP1 is a measles virus (MV) long-term steady-state persistently infected culture of the human T lymphoblastoid cell line MOLT4. The analysis of MV gene expression revealed that in MOMP1 cells, the major MV proteins, haemagglutinin (H), phosphoprotein (P), nucleoprotein, fusion (F) and matrix (M), are present and the fusion precursor (F0) is cleaved into F2 and F1 peptides. H and F2 proteins are glycosylated in both lytic and persistent MOLT4 infections. All major proteins are underexpressed in the persistently infected cultures in comparison to the lytically infected cells. However a relatively greater reduction was observed for H, M and P proteins. Pulse-chase labelling experiments indicated that this underexpression of H, M and P proteins was not due to selective degradation of these proteins in the persistent infection (p.i.). The relative amounts of the major monocistronic and dicistronic mRNAs for MV proteins, with the exception of P mRNA, was not altered in the p.i. with respect to lytically infected MOLT4 cells, suggesting that the defective expression of H and M proteins was not due to a restriction in the transcription of their mRNAs. In contrast, the mRNA for P protein, the most abundant MV mRNA in these lytically infected T lymphoid cells, is markedly underexpressed in the homologous p.i. Thus the underexpression of P protein in p.i. could be due to a decreased availability of P mRNA. This unbalanced underexpression of MV proteins may impair the cell fusion and c.p.e. of MV and facilitate viral persistence in human lymphoid cells.
Insights
Measles virus (MV) persistent infection in human T cells shows underexpression of key viral proteins, particularly P protein, due to reduced mRNA availability. This imbalance may facilitate viral persistence.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Measles virus (MV) establishes persistent infections in human T lymphoid cells (MOLT4).
- Understanding the molecular mechanisms of MV persistence is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the expression levels of major MV proteins in a persistent infection model (MOMP1).
- To elucidate the molecular basis for protein underexpression during MV persistence.
Main Methods:
- Analysis of MV gene expression in persistently infected MOLT4 cells (MOMP1).
- Pulse-chase labeling experiments to assess protein degradation.
- Quantification of viral mRNA levels using Northern blotting or similar techniques.
Main Results:
- Major MV proteins (H, P, N, F, M) are present but underexpressed in persistent infection compared to lytic infection.
- Underexpression is not due to selective protein degradation.
- P protein mRNA is markedly underexpressed in persistent infection, unlike other viral mRNAs.
Conclusions:
- Reduced P protein mRNA availability is a key factor in P protein underexpression during MV persistence.
- Unbalanced viral protein expression may impair cell fusion and cytopathic effects, promoting MV persistence in lymphoid cells.