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The nonstructural C protein is not essential for multiplication of Edmonston B strain measles virus in cultured cells
1Institut für Molekularbiologie, Abteilung 1, Universität Zürich, Hönggerberg, Switzerland.
Abstract:
Measles virus (MV) is a highly contagious agent which causes a major health problem in developing countries. Efficacious and safe live attenuated vaccine strains are available, but for the elimination of measles a better knowledge about the molecular biology of MV appears crucial. Whereas the roles of the six structural proteins in the replication cycle are known, the functions of the two nonstructural proteins C and V are unclear, which is also true for related viruses. In vitro studies implicating Sendai virus suggest that the C protein might be involved in downregulating viral mRNA synthesis (J. Curran, J.B. Marq, and D. Kolakofsky, Virology 189, 647-656, 1992). However, not all members of the Paramyxovirinae subfamily encode this protein, raising the question about its importance for the viral replication cycle. Taking advantage of a recently developed reverse genetics system allowing MV recovery from cloned DNA (F. Radecke, P. Spielhofer, H. Schneider, K. Kaelin, M. Huber, C. Dötsch, G. Christiansen, and M.A. Billeter, EMBO J. 14, 5773-5784, 1995), the question was addressed whether the C protein is essential for the life cycle of MV. A plasmid was constructed to produce a derivative of the Edmonston B vaccine strain, MV C- EdB, having its C reading frame silenced by two point mutations. The C- mutant MV could indeed be rescued, and it multiplies in cultured cells without obvious impairment.
Insights
Measles virus (MV) nonstructural C protein is not essential for viral replication. A modified MV vaccine strain lacking functional C protein multiplies effectively in cell cultures, challenging previous assumptions.
Area of Science:
- Virology
- Molecular Biology
- Vaccinology
Background:
- Measles virus (MV) poses a significant global health challenge, particularly in developing nations.
- While live attenuated vaccines exist, understanding MV's molecular biology is key for eradication.
- The functions of MV nonstructural proteins C and V remain largely unknown.
Purpose of the Study:
- To investigate the essentiality of the MV nonstructural C protein for viral replication.
- To determine if the C protein is indispensable for the measles virus life cycle.
Main Methods:
- Utilized a reverse genetics system for MV recovery from cloned DNA.
- Constructed a plasmid to generate an MV C-deficient mutant (MV C- EdB) via point mutations.
- Assessed the replication capacity of the C-deficient MV mutant in cultured cells.
Main Results:
- Successfully rescued a measles virus mutant with a silenced C protein reading frame (MV C- EdB).
- The MV C-deficient mutant demonstrated unimpaired multiplication in cultured cells.
- This finding suggests the C protein is not essential for MV replication in vitro.
Conclusions:
- The nonstructural C protein is not essential for the measles virus life cycle.
- Further research is needed to elucidate the precise roles of the C protein in MV pathogenesis or other functions.
- These findings contribute to a deeper understanding of measles virus molecular biology.
