The bluetongue virus core: a nano-scale transcription machine.
The replication phase of the bluetongue virus (BTV) infection cycle is initiated when the virus core is delivered into the cytoplasm of a susceptible host cell. The 10 segments of the viral genome remain packaged within the core throughout the replication cycle, helping to prevent the activation of host defence mechanisms that would be caused by direct contact between the dsRNA and the host cell cytoplasm. However, the BTV core is a biochemically active 'nano-scale' machine, which can simultaneously and repeatedly transcribe mRNA from each of the 10 genome segments, which are packaged as a liquid crystal array within a central cavity. These mRNAs, which are also capped and methylated within the core, are extruded into the cytoplasm through pores at the vertices of the icosahedral structure, where they are translated into viral proteins. One copy of each of the viral mRNAs is also assembled with these newly synthesised proteins to form nascent virus particles, which mature by a process that involves -ve RNA strand synthesis on the +ve stand template, thereby reforming dsRNA genome segments within progeny virus cores. The structure of the BTV core particle has been determined to atomic resolution by X-ray crystallography, revealing the organisation and interactions of its major protein components (VP3(T2)-subcore shell and VP7(T13) outer core layer) and important features of the packaged dsRNA. By soaking crystals of BTV cores with metal ions and substrates/products of the transcription reactions prior to analysis by X-ray crystallography, then constructing difference maps, it has been possible to identify binding sites and entry/exit routes for these ions, substrates and products. This has revealed how BTV solves the many logistical problems of multiple and simultaneous transcription from the 10 genome segments within the confined space of the core particle. The crystal structure of the BTV core has also revealed an outer surface festooned with dsRNA. This may represent a further protective strategy adopted by the virus to prevent host cell shut-off, by sequestering any dsRNA that may be released from damaged particles.
Mertens
Peter P C
PP
Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Woking GU24 0NF, UK.
Diprose
Jonathan
J
D000818:Animals; D001665:Binding Sites; D001820:Bluetongue virus / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure*; D018360:Crystallography, X-Ray; D006801:Humans; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008958:Models, Molecular; D014158:Transcription, Genetic; D014758:Viral Core Proteins / Q000737:chemistry; D014779:Virus Replication
D046911:Macromolecular Substances; D014758:Viral Core Proteins