Bluetongue virus proteins and particles and their role in virus entry, assembly, and release

Bluetongue disease in sheep, goats, cattle, and other domestic animals, as well as wild ruminants (e.g., blesbuck, white-tailed deer, elk, and pronghorn antelope), was first described in the late eighteenth century. In sheep, the disease is acute and mortality is accordingly high. For many decades, the disease was believed to be confined to Africa and by early 1900 the disease was reported to be caused by a virus. To date, bluetongue virus (BTV) has been isolated from many tropical, subtropical, and temperate zones and some 24 different serotypes have been identified from different parts of the world. BTV and other related viruses with similar morphological (doughnut-shaped capsomers) and physiochemical properties were grouped together into a distinct genus, the orbiviruses. Orbiviruses occur within the family Reoviridae because of the characteristic double-stranded and segmented features of their RNA genomes (Verwoerd, 1969; Verwoerd et al., 1970, 1972). The Reoviridae family is one of the largest families of viruses and includes major human pathogens (e.g., rotavirus) as well as other vertebrate, plant, and insect pathogens. However, unlike the mammalian reoviruses, orbiviruses, comprising 14 serogroups, are vectored to (Verwoerd, 1969) a variety of vertebrates by arthropod species (e.g., gnats, mosquitoes, and ticks) and replicate in both hosts. BTV is transmitted by Culicoides species and because of its economic significance BTV has been the subject of extensive molecular, genetic, and structural study. As a consequence it now represents one of the best characterized viruses. Unlike the reovirus and rotavirus particles, the mature BTV particle is relatively fragile and the infectivity of BTV is lost easily under mildly acidic conditions. BTV virions (550S) are architecturally complex structures composed of seven discrete proteins organized into two concentric shells, the inner and outer capsids (Hewat et al., 1992b; Mertens et al., 1987; Verwoerd, 1969; Verwoerd et al., 1972) (Fig. 1). The virion proteins encapsidate a genome of 10 double-stranded (ds) RNA segments. The outer capsid, which is composed of two major structural proteins (VP2 and VP5), is involved in cell attachment and virus penetration during the initial stages of infection (Eaton and Crameri, 1989; Hassan and Roy, 1999; Hassan et al., 2001). Shortly after infection, BTV is uncoated (VP2 and VP5 are removed) to yield a transcriptionally active 470S core particle which is composed of two major proteins (VP7 and VP3) and three minor proteins (VP1, VP4, and VP6) in addition to the dsRNA genome (Huismans et al., 1987b). There is no evidence that any trace of the outer capsid remains associated with these cores, as has been described for reovirus (Silverstein et al., 1972). The cores may be further uncoated to form 390S subcore particles that lack VP7, also in contrast to reovirus. Subviral particles are probably akin to cores derived in vitro from virions by physical or proteolytic treatments that remove the outer capsid and cause activation of the BTV transcriptase (Van Dijk and Huismans, 1980). In addition to the seven structural proteins, three nonstructural (NS) proteins, NS1, NS2, and NS3 (and a related protein, NS3A), are synthesized in BTV-infected cells (Huismans and Els, 1979; Roy, 1996, 2001). Of these, NS3/NS3A is involved in the egress of the progeny virus. The two remaining nonstructural proteins, NS1 and NS2, are produced at high levels in the cytoplasm and are believed to be involved in virus replication, assembly, and morphogenesis. This article summarizes the current understanding of the three-dimensional structure of BTV particles, subviral particles, and proteins and their role in the various stages of the virus life cycle. © 2005 Elsevier Inc. All rights reserved.