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Analysis of purified Rift Valley fever virus (RVFV) particles demonstrated the presence of three negativesense RNA genomes, plus three anti-viral-sense RNA segments. The virion-associated anti-viral-sense S segment served as a template for the synthesis of NSs mRNA immediately after infection. NSs protein synthesis also occurred early in infection, suggesting that NSs protein produced early in infection probably has biologically significant roles in virus replication and/or survival in the host. Translation inhibitor treatment of mammalian cells infected with viruses belonging to the Bunyaviridae family generally inhibits viral mRNA synthesis. However, RVFV NSs mRNA synthesis, but not N mRNA synthesis, was resistant to puromycin treatment during primary transcription, pointing to the uniqueness of RVFV NSs mRNA synthesis.Viruses belonging to the Bunyaviridae family carry three single-stranded RNAs, designated L, M, and S. Viral RNA synthesis occurs in the cytoplasm, and the host mRNA-derived cap structure is used as a primer for viral mRNA synthesis (16). Host protein synthesis is essential for viral RNA replication (2,5,6,15,18) and is also important for viral mRNA synthesis in mammalian cells; viral mRNA elongation, but not initiation, is suppressed in the presence of protein synthesis inhibitors (2,15,18). How the host protein synthesis machinery facilitates viral mRNA elongation is unknown; it has been suggested that ribosome binding to nascent viral mRNA prevents its annealing to the template RNA and allows mRNA elongation (2).Rift Valley fever virus (RVFV) (family Bunyaviridae, genus Phlebovirus) causes severe epidemics among ruminants in the sub-Saharan African and has spread to Egypt, Yemen, and Saudi Arabia. It is also an important human pathogen that causes a syndrome of fever and myalgia, a hemorrhagic syndrome, ocular disease, and encephalitis (1, 13). The anti-viralsense L segment encodes L protein, a viral RNA polymerase, and the anti-viral-sense M segment encodes two structural glycoproteins, G1 and G2, NSm protein, and a 78-kDa protein.As in other viruses of the genus Phlebovirus, RVFV S segment uses an ambisense strategy to express N and NSs proteins, and the viral-sense S and anti-viral-sense S segments serve as templates for N mRNA and NSs mRNA, respectively (16). It has been believed that NSs mRNA is produced only after viralsense RNA has been copied to anti-viral-sense RNA; therefore, the NSs protein would appear at a later stage in infection than the structural proteins (6, 16).RVFV NSs protein plays an important role in RVFV pathogenesis and replication. This protein inhibits host mRNA synthesis, including alpha/beta interferon (IFN-␣/␤) mRNAs (3, 10), hence suppressing host innate immune responses to viral invasion, and it is a major virus virulence factor (4). We showed that coexpression of RVFV NSs protein with N and L proteins enhances viral RNA accumulation in the RVFV minigenome system (7). Because this effect appears to be independent of the NSs-mediated inhibition of IFN-␣/␤ produc...

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