From:   Roy, P. (2008)   Structure and Function of Bluetongue Virus and its Proteins. Chapter 4 In: Segmented Double-stranded RNA Viruses. Patton J.T. (Ed.) Caister Academic Press, UK

Bluetongue virus (BTV) is well characterized both genetically (the sequence was completed in 1989) and structurally. Understanding of the molecular biology of the virus and mapping the role of each protein in virus life cycle has benefited significantly through the availability of recombinant BTV proteins and sub-viral particles. In addition the structure of BTV proteins, core and virionparticles have contributed greatly to understanding the mechanism of protein–protein interaction in the virus assembly pathway of BTV and other orbiviruses. Most importantly, information gained from these studies has laid sound foundation for the generation of safe BTV vaccines with the possibility of use in animals in the near future. Latterly, studies have concentrated on the fundamental mechanisms that are used by the virus to invade, replicate in and escape from susceptible host cells. Progress has been made in understanding the structure and entry of intact virus particles, the role of each enzymatic protein in the transcription complex, the critical interactions that occur between the viral non-structural proteins and viral RNA and the role of cellular proteins in non-enveloped virus egress.

Despite these advances, some critical questions remain unanswered for the BTV life cycle and a more complete understanding of the interactions between the virus and the host cell is required for these to be addressed. For example, although progress has been made in the identification of signals for the recruitment of BTV RNA segments into the virion assembly site in the host cell cytoplasm, it has not been possible yet to determine how exactly each genome segment is packaged into the progeny virus. It is also not apparent when and how these genome segments wrap around the polymerase complex once the RNA has been recruited. One of the major drawbacks of research with BTV and other members of Reoviridae has been the lack of availability of a suitable system for genetic manipulation of the virus. This has been a major obstacle in understanding the replication processes of these viruses. However, one of the recent developments in the field of BTV research has been to rescue live virus from transfection of BTV transcripts. There is no doubt that this will be soon extended to establish in vitro manipulative genetic system and will be utilized to address some of these remaining questions.

Very little is known of the intracellular trafficking of newly generated virions although there are some indications of involvement of the cytoskeleton, intermediate filaments and vimentin during BTV morphogenesis. Host–virus interactions during virus trafficking will be one of the future areas needing intense attention. Recent work has revealed unexpected and striking parallels between the entry and release pathways of BTV and pathways involved in entry and release of enveloped viruses. These parallels may be the result of an enveloped ancestor virus or because there are a limited number of cellular pathways that can be useful for the egress of large protein complexes from cells. It is notable that the NS3 glycoprotein of BTV is an integral membrane protein that is functionally involved in virus egress by bridging between the outer capsid protein VP2 and the cellular export machinery. Although no cell-free enveloped form of BTV has been isolated, budding of BTV particles from infected cells at the plasma membrane are quite apparent. The exact role of NS3 in this process and the role of host proteins (Annexin II and p11, Tsg101 and MVB) and their contribution in the release of non-enveloped viruses, such as BTV, remains to be clarified.

More information     Bluetongue Virus (Protein Structure and Molecular Biology)