Rescue of Infectious Rift Valley Fever Virus Entirely from cDNA, Analysis of Virus Lacking the NSs Gene, and Expression of a Foreign Gene

Abstract

Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) has a tripartite negative-strand genome, causes a mosquito-borne disease that is endemic in sub-Saharan African countries and that also causes large epidemics among humans and livestock. Furthermore, it is a bioterrorist threat and poses a risk for introduction to other areas. In spite of its danger, neither veterinary nor human vaccines are available. We established a T7 RNA polymerase-driven reverse genetics system to rescue infectious clones of RVFV MP-12 strain entirely from cDNA, the first for any phlebovirus.

Curcumin Inhibits Rift Valley Fever Virus Replication in Human Cells

“…Experiments carried out using the virulent ZH501 strain demonstrate that curcumin can inhibit replication of the fully virulent virus as well. Finally, our experiments using the INFAR Ϫ/Ϫ murine model (28,29) provide preliminary proofof-concept validation that curcumin can down-regulate virus in the livers of infected animals as well, thus paving the way for further development of novel curcumin-based therapeutic options.…”

“…ϭ 3). In the case of infections with the NSs and NSm mutant viruses (6,28), cells were infected with the appropriate mutant constructs (m.o.i. ϭ 3).…”

Rift Valley fever virus MP-12 vaccine encoding Toscana virus NSs retains neuroinvasiveness in mice

“…MP-12 NSs is fully functional (Billecocq et al, 2008;Ikegami et al, 2006Ikegami et al, , 2009Kalveram et al, 2011a) and is dispensable for vaccine efficacy in mice (Lihoradova et al, 2012). Potential disadvantages of MP-12 lacking NSs is a slightly lower level of neutralizing antibody in vaccinated ruminants (Morrill et al, 2013) and inefficient replication in MRC-5 cells, which have been used for MP-12 amplification for vaccine manufacturing (Ikegami et al, 2006;Lokugamage et al, 2012). Therefore, we attempted to replace MP-12 NSs with that of a serologically distinct phlebovirus.…”

A Glycoprotein Subunit Vaccine Elicits a Strong Rift Valley Fever Virus Neutralizing Antibody Response in Sheep

“…Strategies to develop RVFV vaccines include subunit (Schmaljohn et al 1989, Mandell et al 2010a, DNA (Spik et al 2006), viruslike particles (VLPs) , de Boer et al 2010, Kortekaas et al 2012, virus replicon particles (Kortekaas et al 2011, Dodd et al 2012, Oreshkova et al 2013), virus-vectored (Wallace et al 2006, Heise et al 2009) modified live vaccines, developed from recombinant viruses engineered using reverse genetics (Ikegami et al 2006, Bird et al 2008, Billecocq et al 2008, Habjan et al 2008, Bird et al 2011, live attenuated (Smithburn 1949, Caplen et al 1985, Muller et al 1995, Dungu et al 2010, Pittman 2012, Morrill et al 2013, and inactivated whole virus vaccines (Pittman et al 2000). Although subunit vaccines for RVFV are generally considered safe, and recently some progress has been made in their development, evaluation of immunogenicity and/or efficacy in a target species, sheep, has been performed for a few candidates (Kortekaas et al 2012, Oreshkova et al 2013).…”