Rift Valley fever virus is a negative sense single stranded RNA virus with a tripartite genome consisting of small (S), medium (M), and large (L) segments [16
]. It is a member of the genus Phlebovirus
in the family Bunyaviridae
. Cryoelectron tomography has recently revealed that RVFV, once thought to be pleomorphic, has, an icosahedral structure, with a T=12 triangulation number. Among viruses, this type of structure is only known to occur in Uukuniemi virus, a related phlebovirus [17
]. Analysis of RVFV strains collected during the recent Kenyan outbreak in 2006-2007 has demonstrated the concurrent circulation of multiple virus lineages that manifest gene segment reassortments but share common ancestry from the 1997-1998 East African outbreak of RVF [18•
]. This analysis also indicated continuing RVF virus circulation and evolution during the 1998-2006 interepizootic/epidemic period. Of note, wildlife surveys in Kenya have further demonstrated the continued circulation of RVFV among many different types of wildlife during inter-epizootic periods [19
]. Additional research is needed to evaluate the significance of these wild vertebrate species in maintaining RVFV transmission in high-risk ecosystems.
Many bunyaviruses, including RVFV, produce a non-structural protein encoded by the S gene segment, known as NSs protein, which serves as an important virulence factor [20
]. NSs protein is known to interfere with host transcription and antagonize beta- interferon (IFN-β) production, thereby limiting early phases of host innate immunity and likely increasing pathogenesis [24
]. A new role for NSs protein was recently defined; beyond IFN-β suppression, NSs protein was also found to downregulate dsRNA-dependent protein kinase (PKR), a ubiquitous protein that suppresses viral translation in response to viral replication [27
]. By downregulating PKR, RVFV is able to effectively translate its viral proteins and replicate despite deficient cellular transcription. This downregulation of PKR was shown to be due to the degradation of PKR via the proteasome [21
]. Finally, an additional virulence factor, the NSm protein (a non-structural protein encoded on the M segment of RVFV) has been shown to suppress viral-induced apoptosis of infected cells [28
Although RVFV replicates in host cell cytoplasm, it has been known that NSs protein forms filamentous structures in the nuclei of infected cells [29
]. A recent study has elucidated the importance of Sin3A-associated protein 30 (SAP30) and NSs interactions in host cell nuclei [26
]. After RVFV infection a multi-protein complex containing NSs protein and host transcription factors, SAP30 and YY1, the activator/repressor of interferon transcription, along with other cofactors allows for repression of the IFN-β promoter and evasion of host antiviral response. Another recent study has demonstrated that NSs interacts with constitutive heterochromatin clusters of pericentromeric DNA sequences in host cells [23•
]. Formation of NSs filaments (phosphorylated multimers of NSs protein) enhances interaction with heterochromatin and leads to chromosome cohesion and segregation defects, which is dependent on SAP30 interaction. This finding reinforces previous observations concerning the main role of NSs-SAP30 interaction on RVFV pathogenicity, and may help to explain the mechanism by which RVFV causes abortions and fetal deformities in infected animals.