Bluetongue (BT) is a hemorrhagic disease of ruminants caused by bluetongue virus (BTV), the prototype member of the genus Orbivirus within the family Reoviridae and is transmitted via biting midges of the genus Culicoides. BTV can be found on all continents except Antarctica, and up to 26 immunologically distinct BTV serotypes have been identified. Live attenuated and inactivated BTV vaccines have been used over the years with different degrees of success. The multiple outbreaks of BTV in Mediterranean Europe in the last two decades and the incursion of BTV-8 in Northern Europe in 2008 has re-stimulated the interest to develop improved vaccination strategies against BTV. In particular, safer, cross-reactive, more efficacious vaccines with differential diagnostic capability have been pursued by multiple BTV research groups and vaccine manufacturers. A wide variety of recombinant BTV vaccine prototypes have been investigated, ranging from baculovirus-expressed sub-unit vaccines to the use of live viral vectors. This article gives a brief overview of all these modern approaches to develop vaccines against BTV including some recent unpublished data.

Bluetongue is a major infectious disease of ruminants caused by bluetongue virus (BTV), an arbovirus transmitted by Culicoides. Here, we assessed virus and host factors influencing the clinical outcome of BTV infection using a single experimental framework. We investigated how mammalian host species, breed, age, BTV serotypes, and strains within a serotype, affect the clinical course of bluetongue. Results obtained indicate that in small ruminants there is a marked difference in the susceptibility to clinical disease induced by BTV at the host species level, but less so at the breed level. No major differences in virulence were found between divergent serotypes (BTV-8 and BTV-2). However, we observed striking differences in virulence between closely related strains of the same serotype collected towards the beginning and the end of the European BTV-8 outbreak. As observed previously, differences in disease severity were also observed when animals were infected with either blood from a BTV-infected animal or from the same virus isolated in cell culture. Interestingly, with the exception of two silent mutations, full viral genome sequencing showed identical consensus sequences of the virus before and after cell culture isolation. However, deep sequencing analysis revealed a marked decrease in the genetic diversity of the viral population after passaging in mammalian cells. In contrast, passaging in Culicoides cells increased the overall number of low frequency variants compared to virus never passaged in cell culture. Thus, Culicoides might be a source of new viral variants and viral population diversity can be another factor influencing BTV virulence.IMPORTANCE Bluetongue is one of the major infectious diseases of ruminants. It is caused by an arbovirus known as Bluetongue virus (BTV). The clinical outcome of BTV infection is extremely variable. We show that there are clear links between the severity of bluetongue and the mammalian host species infected, while at the breed level differences were less evident. No differences were observed in the virulence of two different BTV serotypes (BTV-8 and BTV-2). In contrast, we show that the European BTV-8 strain isolated at the beginning of the bluetongue outbreak in 2006 was more virulent than a strain isolated towards the end of the outbreak. In addition, we show that there is a link between the variability of the BTV population as a whole and virulence and our data also suggest that Culicoides cells might function as an "incubator" of viral variants.

Foot-and-mouth disease (FMD) is one of the most highly contagious diseases of animals. The disease is distributed on three continents (Asia, Africa and South America) where it disrupts the food security of people who depend on livestock and animal products. Substantial economic losses are associated with controlling FMD outbreaks in many countries. For example, during the epidemic in the UK in 2001, losses to agriculture were estimated to be £3.1 billion, with similar losses arising from negative impacts on tourism. Over 4 million animals were slaughtered as part of FMD control measures and a further 2 million were slaughtered due to welfare issues associated with animal movement bans. FMD also has a devastating impact on rural livelihoods and livestock trade opportunities in developing countries where it is endemic. In Africa, historic patterns of FMD virus (FMDV) emergence are likely to have been shaped by the introduction and subsequent eradication of rinderpest. However, important questions remain about contemporary drivers of disease distribution. In particular, the relative contribution of wildlife as sources of infection for livestock and factors affecting the potential for cross-species transmission, and mechanisms of viral maintenance in endemic regions are poorly understood. These issues encompass a complex suite of interacting social, ecological and economic factors that act as drivers of change in patterns of land-use, livestock movements, international trade, and conservation of wildlife-protected areas. Understanding patterns of FMDV infection at the livestock-wildlife interface is of particular importance for designing and developing appropriate disease control strategies in sub-Saharan Africa, and of increasing interest as momentum grows for global control of FMD within the framework of the Progressive Control Pathway (PCP-FMD). This chapter reviews the historical distribution and emergence of FMDV in Africa, and factors that govern the current circulation and maintenance of FMDV in sub-Saharan Africa.

The V proteins of paramyxoviruses are composed of two evolutionarily distinct domains, the amino-terminal 75% being common to the viral P, V and W proteins and not highly conserved between viruses, while the remaining 25% consists of a cysteine-rich V-specific domain which is conserved across almost all paramyxoviruses. There is evidence supporting a number of different functions of the V proteins of morbilliviruses in blocking the signalling pathways of type I and II interferons, but it is not clear which domains of V are responsible for which activities, and whether all these activities are required for effective blockade of interferon signalling. We show here that the two domains of rinderpest virus V protein have distinct functions, the N-terminal domain acting to bind STAT1 while the C-terminal V-specific domain interacts with the interferon-receptor associated kinases Jak1 and Tyk2. Effective blockade of interferon signalling required the intact V protein.