M protein instability and lack of H protein processing associated with nonproductive persistent infection of HeLa cells by measles virus
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Abstract:
Persistent infections such as subacute sclerosing panencephalitis (SSPE) which do not produce infectious virus particles (nonproductive persistence) are often accompanied by a reduced steady-state amount of the viral matrix (M) protein and/or reduced hemadsorption activity. The possible causes of these aberrations associated with nonproductive persistence were investigated by following changes in the viral proteins with time in pulse-chase experiments. Three HeLa cell lines persistently infected with measles virus; K11, K11A, and HG111; were compared to each other and to acutely infected HeLa cells. K11 produces infectious virions at a low level (productive persistence). K11A and HG111 are both nonproductive persistently infected cell lines derived from K11. K11A cells have a reduced steady-state amount of viral M protein and reduced hemadsorption activity. HG111 cells have reduced hemadsorption but a normal level of viral M protein. As such, these cell lines serve as good model systems for the study of nonproductive persistent infection associated with SSPE. The reduced amount of M protein in K11A was found to result from rapid degradation of the protein. Degradation of the protein resulted from changes in the protein itself rather than from cellular changes. The hemagglutination (H) protein was found to be present at a low level in K11A cells. In addition, in both K11A and HG111 cells, conversion of the sugar moiety of the H glycoprotein from the high mannose form to the complex sugar form did not take place. Such modification usually occurs concomitant with transport of glycoproteins onto the cell surface. As such, lack of processing could preclude the appearance of functional H proteins on the cell surface. This could account for the reduced hemadsorption activity in these cells. The roles that these changes may play in the generation of nonproductive persistence are discussed.
Insights
Persistent measles virus infections can lead to nonproductive persistence, characterized by reduced viral matrix (M) protein and hemadsorption. This study reveals rapid M protein degradation and impaired H glycoprotein processing contribute to these changes, offering insights into subacute sclerosing panencephalitis.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Persistent viral infections, like subacute sclerosing panencephalitis (SSPE), often exhibit nonproductive persistence, marked by diminished viral matrix (M) protein and hemadsorption.
- Understanding the molecular mechanisms behind nonproductive persistence is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the causes of reduced viral M protein and hemadsorption activity in nonproductively persistent measles virus infections.
- To utilize distinct HeLa cell lines (K11, K11A, HG111) as models for studying nonproductive viral persistence.
Main Methods:
- Pulse-chase experiments were employed to track viral protein dynamics over time in acutely and persistently infected HeLa cells.
- Comparative analysis of viral protein levels and glycoprotein processing in productive (K11) versus nonproductive (K11A, HG111) persistent infection models.
Main Results:
- Nonproductive cell lines K11A and HG111 exhibited reduced hemadsorption activity.
- K11A cells showed a decreased steady-state level of viral M protein due to rapid protein degradation, stemming from intrinsic protein changes.
- Both K11A and HG111 cells displayed impaired processing of the H glycoprotein, preventing its conversion to complex sugars and subsequent cell surface transport, thus explaining reduced hemadsorption.
Conclusions:
- Rapid degradation of the viral M protein and defective H glycoprotein processing are key factors contributing to nonproductive measles virus persistence.
- These molecular aberrations provide a cellular basis for understanding the pathogenesis of SSPE and related persistent viral diseases.
- The studied HeLa cell lines serve as valuable models for further research into the mechanisms of nonproductive viral persistence.