Functional analyses of capsid regions in rubella virus replication.

摘要

Rubella virus (RV) is a small enveloped positive strand RNA virus that belongs to the family the Togaviridae. It is the etiological agent of rubella, a generally mild self-limiting disease that is also known as German measles. However, RV is the most teratogenic infectious agent known, and in utero infection during the first trimester of pregnancy, often results in severe malformations to the human fetus. Despite its medical significance, the biology of RV is not well understood. To this end, our laboratory is focused on the role of the capsid protein in virus assembly and host cell interactions. Capsid is a major structural component of rubella virions. During virus assembly, the functions of RV capsid are to package the RNA genome and to interact with the virus glycoproteins. These heterotypic binding reactions are required to coordinate nucleocapsid formation and drive virus budding respectively. In addition to its structural roles, capsid protein has been shown to modulate genome replication most likely through interactions with nonstructural proteins. In addition, capsid binds to a variety of host cell proteins and thus may be an important factor in virus-host interactions.; In the present study, the roles of two capsid regions in RV replication are investigated. First, I showed that the hydrophobic carboxyl terminus of capsid is required for membrane association of this protein. Moreover, my data indicate that this domain is required for transport of capsid to the juxtanuclear region where virus budding occurs. Secondly, I mapped a group of phosphorylated amino acid residues to the RNA binding site of capsid. Phosphorylation of serine 46 is critical for downstream phosphorylation of other amino acid residues in capsid. Dynamic phosphorylation of capsid appears to regulate the RNA binding activity of this protein and ultimately virus replication. In summary, this work provides the basis for a mechanistic understanding of the spatial and temporal interactions of capsid during virus assembly.