[Rift Valley fever virus infection : physiopathology and pathogenesis]. / Infection par le virus de la fièvre de la vallée du Rift : physiopathologie et pathogenèse.

Rift Valley fever (RVF) is a major emerging arboviral disease with a complex epidemiological cycle. RVF virus (RVFV) is transmitted by mosquito vectors to ruminants, causing epizootics, and then from animals to humans, triggering epidemics. During its cycle, RVFV infects a wide range of hosts, but the associated pathogenesis has yet to be elucidated. RVFV displays a predominant hepatic tropism, but also has a multicellular tropism inducing physiopathological effects in several tissues. However, there is variability between species in terms of physiopathology : a common clinical picture is found (severe hepatitis, hemorrhages, leukopenia), but certain forms are mainly found in humans (neurological and ocular damage) or in ruminant herds (waves of abortions). Although the molecular mechanisms involved are still poorly understood, it seems that early inflammatory response is related to the severity of the pathology. A better understanding of the pathogenesis of RVFV seems essential, especially since no specific treatment exists to date.

Rift Valley fever virus modulates apoptosis and immune response during infection of human astrocytes.

Rift Valley fever (RVF) is an arboviral disease of zoonotic origin that causes recurrent epidemics in Africa, the Arabic Peninsula, and islands of the South West of the Indian Ocean. RVF occurs mainly in livestock but also affects humans with severe clinical manifestations, including neurological disorders. However, human neuropathogenesis of Rift Valley fever virus (RVFV) is still poorly characterized. To study the interactions between RVFV and the central nervous system (CNS), we focused on RVFV infection of astrocytes, the major glial cells of the CNS that have several supporting roles including immune response regulation. We confirmed the permissiveness of astrocytes to RVFV infection and highlighted a strain-dependent infectivity. We showed that RVFV infection of astrocytes induced cell apoptosis and observed that the RVFV Non-Structural protein NSs, a known virulence factor, potentially delayed apoptosis by sequestrating activated-caspase 3 in the nucleus. Our study also showed that RVFV-infected astrocytes upregulated expression of genes associated with inflammatory and type I interferon responses at the mRNA level, but not at the protein level. This inhibition of immune response is potentially due to a NSs-dependent mechanism of mRNA nuclear export inhibition. Together, these results highlighted the direct impact of RVFV infection on the human CNS through the induction of apoptosis and a possible inhibition of early-onset immune responses that are crucial for the host survival.

Rift Valley fever in West Africa: A zoonotic disease with multiple socio-economic consequences.

Rift Valley fever virus (RVFV) is an arbovirus that causes Rift Valley fever (RVF), a zoonotic disease that mainly affects domestic and wildlife ruminants and humans. The first epidemic in North-Western and West Africa occurred in Senegal and Mauritania in 1987, two countries where RVF is now endemic. Slaughterhouse workers, farmers, herders and veterinarians are at high risk of exposure to RVF. Beyond the health threat, RVF is considered to cause major socio-economic problems, specifically in developing countries where livestock farming and trade are important economic activities. Indeed, the mortality rate linked to RVF infection can reach 95-100% in newborns and young animals. In West Africa, livestock production is a key factor for food production and for national economics. Epizootics caused by RVF can therefore have serious socio-economic consequences by impacting multisectoral economics, the psycho-social health of pastoral communities, and food security. Improving prevention strategies against RVF, including vaccination, enhancing knowledge of RVF and correcting any inappropriate behaviors by populations of endemics areas, as well as better monitoring of RVF ecological factors are effective ways to better foresee and control outbreaks of RVF and its socio-economical side-effects in countries at high risk of occurrence of the disease.