Oropouche virus (OROV) belongs to the family Bunyaviridae, genus Orthobunyavirus, serogroup Simbu, and is the second most frequent cause of arboviral illness in Brazil, surpassed only by dengue. OROV is transmitted by the bite of the vector Culicoides paraensis and causes acute febrile disease in humans, with significant public health impact, mainly in the Amazon. OROV genome is composed by 3 RNA segments (L, M e S) coding for 3 structural proteins, plus the polymerase and 2 other nonstructural proteins - NSm e NSs. NSs is a virulence factor for other members of the genus Orthobunyavirus, but very little is known about NSm. Evidence from studies done with other Bunyaviridae have shown that NSm plays roles in assembly and morphogenesis of virus particles, and also is synergic with NSs in the control of interferon response to Schmallemberg virus, which is also in the genus Orthobunyavirus. However, nothing is known about the functions of NSm in OROV. This project aims at investigating the role of OROV NSm in virus-cell interaction at cellular and organismal levels using in vitro and in vivo models. We want to determine the cellular localization of NSm during OROV replication; characterize in vitro and in vivo the effects of OROV devoid of NSm (rOROVNSm); analize the effect of heterologous expression of NSm, as well as the co-expression of NSm and NSs in mammal and arthropod cells; make OROV and rOROVNSm tagged with a fluorescent protein to study dispersal and pathogenesis in experimental animals by intra-vital microscopy. This PhD project is part of the FAPESP Thematic Projetct process 2014/02438-6, coordinated by Prof. Dr. Luiz Tadeu Moraes Figueiredo.
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