Molecular and Structural Insights into the Life Cycle of Rubella Virus

Rubella virus (RUBV), a rubivirus, is an airborne human pathogen that generally causes mild measles-like symptoms in children or adults. However, RUBV infection of pregnant women can result in miscarriage or congenital rubella syndrome (CRS), a collection of long-term birth defects including incomplete organ development and mental retardation. Worldwide vaccination campaigns have significantly reduced the number of RUBV infections, but RUBV continues to be a problem in countries with low vaccination coverage. Further, the recent discovery of pathogenic rubiviruses in other mammals emphasizes the spillover potential of rubella-related viruses to humans. In the last decade, our understanding of RUBV has been significantly increased by virological, biochemical, and structural studies, providing a platform to begin understanding the life cycle of RUBV at the molecular level. This review concentrates on recent work on RUBV, focusing on the virion, its structural components, and its entry, fusion, and assembly mechanisms. Important features of RUBV are compared with those of viruses from other families. We also use comparative genomics, manual curation, and protein homology modeling to highlight distinct features of RUBV that are evolutionarily conserved in the non-human rubiviruses. Since rubella-like viruses may potentially have higher pathogenicity and transmissibility to humans, we also propose a framework for utilizing RUBV as a model to study its more pathogenic cousins.