Influence of the CCR-5/MIP-1 α Axis in the Pathogenesis of Rocio Virus Encephalitis in a Mouse Model

Abstract

Abstract. Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in Brazil and its immunopathogenesis remains poorly understood. CC-chemokine receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory protein (MIP-1 α). Both molecules are associated with inflammatory cells migration during infections. In this study, we demonstrated the importance of the CCR5 and MIP-1 α, in the outcome of viral encephalitis of ROCV-infected mice. CCR5 and MIP-1 α knockout mice survived longer than wild-type (WT) ROCV-infected animals. In addition, knockout mice had reduced inflammation in the brain. Assessment of brain viral load showed mice virus detection five days post-infection in wild-type and CCR5−/− mice, while MIP-1 α−/− mice had lower viral loads seven days postinfection. Knockout mice required a higher lethal dose than wild-type mice as well. The CCR5/MIP-1 α axis may contribute to migration of infected cells to the brain and consequently affect the pathogenesis during ROCV infection.

IL-33 signaling is essential to attenuate viral-induced encephalitis development by downregulating iNOS expression in the central nervous system

“…In two previous studies, we characterized partially the immune response to ROCV infection [ 2 , 3 ]. Here, to better understand the immunopathologic process, we infected BALB/c mice with 1.10 6 PFU ROCV, sacrificed these animals at 5 and 7 days post-infection (p.i.)…”

“…Previous studies from our group demonstrated that ROCV infects and induces in BALB/c mice damage of the central nervous system (CNS), characterized by neuronal degeneration and apoptosis with detectable levels of inflammatory cytokines and massive cellular infiltration [ 2 ]. Moreover, cellular infiltration in CNS is highly dependent of the CCR-5/MIP-1α axis, since CCR5 and macrophage inflammatory protein 1 alpha (MIP-1α) knockout mice presented reduced inflammation with increased survival rates after ROCV infection [ 3 ]. CNS cellular infiltration induced by ROCV infection is characterized by F4/80 + cells, detected early as 4 days post-infection.…”

Review on Infections of the Central Nervous System by St. Louis Encephalitis, Rocio and West Nile Flaviviruses in Brazil, 2004-2014

“…Moreover the knockout mice required a higher lethal dose than those mice of the wild type. The CCR5/MIP-1α axis may contribute to the migration of cells into ROCV infected brains [27]. These findings can help to better understand the pathogenesis and the physiopathology of the human meningoencephalomyelitis by ROCV and other flaviviruses of the JE serocomplex.…”

Historical Perspective and Biotechnological Trends to Block Arboviruses Transmission by Controlling Aedes aegypti Mosquitos Using Different Approaches

“…The first cases of Rocio virus (ROCV) were recorded in the southeastern region of Brazil during a viral encephalitis epidemic that lasted for about 2 years in the 1970s. Although subsequent outbreaks did not occur, there was serological evidence of ROCV circulation, which serves as a warning signal for possible new epidemics (37). La crosse virus (LACV) is present in Latin America and in some regions of North America and is transmitted by mosquitoes of the genus Aedes.…”