Submitted to: Molecular Cell
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/3/2002
Publication Date: 3/1/2002
Citation: Schwartz, M., Chen, J., Janda, M. Sullivan, M.L., Ahlquist, P.G. 2002. A positive-strand RNA virus replication complex parallels form and function of retrovirus capsids. Molecular Cell. 9:505-514. Interpretive Summary: Positive-strand RNA viruses comprise a large proportion of known viruses, many of which cause human and animal disease. Brome mosaic virus (BMV) is a member of a large superfamily of positive-strand RNA viruses that infect humans, animals, and plants and is an extremely useful model system for studying positive-strand RNA viruses. In this report, molecular biology and microscopy approaches were used to understand how BMV assembles the RNA replication complex responsible for viral replication within host cells. The findings of the study indicate that positive-strand RNA viruses, reverse transcribing viruses (including HIV), and double-stranded RNA viruses (including rotaviruses which kills many children in developing countries) use related pathways and structures to replicate their genes even though they seem to take distinct routes to replication. By linking three of the six major classes of viruses, the results offer a significant unification within the field of virology. Further, this research may be a first step in long term goals to devise more general virus control or treatment strategies.
Technical Abstract: We show that brome mosaic virus (BMV) RNA replication protein 1a, 2a polymerase, and a cis-acting replication signal recapitulate the functions of Gag, Pol, and RNA packaging signals in conventional retrovirus and foamy virus cores. Prior to RNA replication, 1a forms spherules budding into the endoplasmic reticulum membrane, sequestering viral positive-strand RNA templates in a nuclease-resistant, detergent-susceptible state. When expressed, 2a polymerase colocalizes in these spherules, which become the sites of viral RNA synthesis and retain negative-strand templates for positive-strand RNA synthesis. These results explain many features of replication by numerous positive strand RNA viruses and reveal that these viruses, reverse transcribing viruses, and dsRNA viruses share fundamental similarities in replication and may have common evolutionary origins.