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Defective particles in alphavirus infections.
Medical Biology
|October 1, 1975
Summary
Defective-interfering particles of Sindbis virus interfere with normal viral replication by competing for essential viral replicase enzymes. These particles contain a larger RNA species that prevents the synthesis of viral structural proteins.
Area of Science:
- Virology
- Molecular Biology
Background:
- Defective-interfering particles (DIPs) of Sindbis virus are generated during high-multiplicity infections.
- These DIPs alter viral RNA metabolism in infected cells.
Purpose of the Study:
- To investigate the characteristics and interference mechanism of Sindbis virus DIPs.
- To understand the role of DIPs in viral RNA synthesis and protein production.
Main Methods:
- High multiplicity passaging of Sindbis virus in BHK cells to generate DIPs.
- Analysis of viral RNA species (20S and 26S RNA) in infected cells.
- Studies of replicative forms and intermediates to infer RNA structure.
- Assessing viral structural protein synthesis in the presence and absence of standard virus.
Main Results:
- Cells infected with DIPs accumulate 20S RNA at the expense of 26S mRNA.
- DIP RNA appears larger than intracellular 20S RNA, though its structure is undefined.
- DIPs do not produce viral structural proteins independently.
- DIPs do not stimulate intracellular viral RNA synthesis.
Conclusions:
- Sindbis virus DIPs interfere with viral replication by competing for viral replicase.
- The accumulation of a larger RNA species in DIPs disrupts normal viral gene expression.