Pathogenesis and neurovirulence of emerging viruses in Brazil

Abstract

Emerging viruses are agents associated with a new or a previous low-prevalent disease in a specific geographic region that significantly increased their incidence that area. Among the emerging viruses in Brazil is possible to highlight: Zika (ZIKV), Oropouche (OROV), Chikungunya (CHIKV), Mayaro (MAYV) and probably La Crosse (LACV), Iquitos virus (IQTV), Japanese Encephalitis (JEV), Saint Louis encephalitis (SLEV) and West Nile virus (WNV). These agents cause a wide spectrum of diseases in humans, from asymptomatic cases, rash febrile illness until severe clinical manifestations, such as neurological syndromes (Guillain-Barré syndrome, meningoencephalitis, flaccid paralysis among others) and congenital syndromes (abortion, fetal malformations, microcephaly, eye and hearing damage and other fetal manifestations). However, the pathogenetic factors associated with the development of these so different clinical outcomes are not completely understood, but it is known that viral replication, the type of infected cells and the immune response triggered early during infection are essential phenomena to the clinical results of a viral infectious process. Thus, the aim of this project is to characterize how cells and key components of the innate immune response, including pattern recognition receptors (TLR RIG, NLR, CGAS, Sting) and molecules induced by them (such as MyD88, IR-5) control the pathogenesis and neurovirulence ZIKV and OROV. For this, we will measure viral replication, immune cell activation and production of inflammatory mediators in patients, human and mice cells isolated in vitro (neutrophils, macrophages and myeloid and plasmacytoid dendritic cells) and wild-type and selected-knockouts (KO) mice infected with ZIKV and OROV. In order to obtain samples from naturally infected humans, this project will support an arbovirus surveillance network conducted by Unicamp since February 2016. This network has monitored patients treated in Campinas, including those with rash febrile illness (children, adults and pregnant women) and neurological manifestations possibly associated viral infection. The approval of this project will set up a referenced laboratory with biosafety-security level 2 (BSL-2) for arbovirus manipulation and detection at Biology Institute of Unicamp. This Lab will support the Universitary Hospital of Campinas and will allow the development of multidisciplinary researches with professors from Medical Science School of Unicamp. In addition, the present study has collaboration with researchers from Washington University in USA and A-Star Institute in Singapore. (AU)