Identification and characterization of interactions between rubella virus capsid and host cell proteins

Rubella virus (RV) is a positive strand RNA virus belonging to the family Togaviridae. It is the etiological agent of German measles, a normally benign human disease. However, when contracted during the first trimester of pregnancy RV is highly teratogenic and causes a series of birth defects known as congenital rubella syndrome. In the developing world, RV remains a major cause of congenital abnormalities. Despite the importance of RV as a human pathogen, the molecular basis of virus disease remains poorly understood. In order to understand the role of individual proteins during RV infection, we have focused our studies on the capsid protein. While the primary function of this protein is to package genomic RNA into nucleocapsids, recent studies have identified several additional roles for capsid. In an attempt to elucidate the mechanisms by which capsid conducts its various functions, we identified a number of host cell proteins that bind to capsid. In addition, we found that capsid expression, in the absence of other viral proteins, affects mitochondrial distribution and morphology. Furthermore, the interaction between capsid and the mitochondrial matrix protein p32 was shown to be important for capsid-induced aggregation of mitochondria. In addition, recombinant viruses encoding capsids with mutations in the p32 binding site displayed altered plaque morphology and replicated poorly suggesting that capsid-p32 interactions are important for virus replication. From this work, it appears that the RV capsid protein plays an even more dynamic role in RV biology than previously suspected.