Insights into Alphavirus Replication

No treatments or vaccines exist for Chikungunya and other disease-causing alphaviruses, all of which are mosquito-borne. The RNA genome of alphaviruses must be selectively packaged so it can be successfully transmitted into host cells. A paper published online on September 17 in Nature Communications by Margaret Kielian, Ph.D., and colleagues describes the likely mechanism by which alphavirus capsid proteins package the viral RNA.

Dr. Kielian and colleagues studied Semliki Forest virus (SFV), an alphavirus that is closely related to Chikungunya virus but does not cause serious disease in people. The researchers scanned the entire RNA genome at various stages of virus assembly to find sites where the virus RNA genome binds with viral capsid proteins. Interestingly, although binding sites changed as virus assembly proceeded, the RNA genome was found to have a single preferential binding site for capsid protein at all stages. This binding site also supported specific assembly of the viral nucleocapsid in vitro. These results challenge the current model of RNA genome packaging in alphaviruses and provide a mechanism of RNA genome assembly at key stages of viral growth.

Dr. Kielian is professor of cell biology and the Samuel H. Golding Chair in Microbiology at Einstein. First author, Rebecca Brown, Ph.D., is a postdoctoral fellow in the Kielian laboratory. Collaborators on the project were Markus Hafner, Ph.D., and Dimitrios Anastasakis, Ph.D., of the National Institutes of Health.