1. Field of the Invention
The present invention relates generally to the field of molecular biology, virology and immunology. More specifically, the present invention provides a reverse genetic system for Rift Valley fever virus (RVFV) and discloses its use in the development of vaccine for Rift Valley fever virus and in the large scale screening of antivirals and developing a marker for Rift Valley fever virus.
2. Description of the Related Art
Rift Valley fever virus causes an endemic disease of sub-Saharan Africa that has emerged in explosive mosquito-borne epidemics resulting not only in massive economic loss in herds of sheep and cattle but also causing hemorrhagic fever, encephalitis, retinal vasculitis and lesser disease in humans. In addition to the epidemics in sub-Saharan Africa, Rift Valley fever virus has been exported to Egypt on multiple occasions, particularly in 1977 when thousands of human infections occurred (Peters and Meegan, 1981). After a large epidemic in Africa in 1997-1998, the virus traveled to Egypt and the Arabian peninsula, menacing further spread (Shoemaker et al., 2002; Woods et al., 2002). The possibilities of introduction in many different countries and of its use as a bioterrorist agent (Peters, 2000) demand the availability of effective protective measures for humans and domestic animals.
It is likely that the disease can only be controlled by an effective live attenuated vaccine for livestock and certainly the control activities will necessitate protection of humans, most likely by vaccination (Peters, 1997). The livestock vaccines that are available are unsatisfactory either because of fetal pathology or lack of immunogenicity and because modern usage of vaccines requires the presence of markers to identify vaccinated animals in contrast to those after natural infection. Furthermore, the development of vaccine is also hampered due to lack of knowledge of the basis of attenuation of the single viable human vaccine candidate (Caplen et al., 1985; Vialat et al., 1997). Another major barrier to the development of vaccine for Rift Valley fever virus is the lack of understanding of the molecular virology of Bunyaviridae and of its medically important genus Phlebovirus. 
Reverse genetics has been established for several RNA virus families, but Arenaviridae and Bunyaviridae have been recalcitrant. Among the family Bunyaviridae, only Bunyamvera virus (BUN) (Bridgen and Elliott, 2001) and La Crosse virus (LAC) (Blakqori and Weber, 2005) belonging to the genus Orthobunyavirus have been successfully recovered from cDNA. So far no viruses from the other four Bunyaviridae genera have been recovered. The Phlebovirus genus, in particular, that has a number of important human and animal pathogens, is poorly understood at the molecular level and unlike other Bunyaviridae has a replication strategy that resembles arenaviruses and utilizes an ambisense coding strategy (Schmaljohn and Hooper, 2001).
Thus, prior art is deficient in a Rift Valley fever virus expression system that can be used to develop vaccines for Rift Valley fever virus, screen antivirals and develop markers for Rift Valley fever virus. The current invention fulfils this long standing need in the art.