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BALB/c mice infected with DENV-2 strain 66985 by the intravenous route display injury in the central nervous system.

ABSTRACT: Dengue is a mild flu-like arboviral illness caused by dengue virus (DENV) that occurs in tropical and subtropical countries. An increasing number of reports have been indicating that dengue is also associated to neurological manifestations, however, little is known regarding the neuropathogenesis of the disease. Here, using BALB/c mice intravenously infected with DENV-2 strain 66985, we demonstrated that the virus is capable of invading and damaging the host's central nervous system (CNS). Brain and cerebellum of infected animals revealed histological alterations such as the presence of inflammatory infiltrates, thickening of pia matter and disorganization of white matter. Additionally, it was also seen that infection lead to altered morphology of neuroglial cells and apoptotic cell death. Such observations highlighted possible alterations that DENV may promote in the host's CNS during a natural infection, hence, helping us to better understand the neuropathological component of the disease.

SUBMITTER: Salomao NG

PROVIDER: S-EPMC6021404 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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BALB/c mice infected with DENV-2 strain 66985 by the intravenous route display injury in the central nervous system.

Salomão Natália G NG Rabelo Kíssila K Póvoa Tiago F TF Alves Ada M B AMB da Costa Simone M SM Gonçalves Antônio J S AJS Amorim Juliana F JF Azevedo Adriana S AS Nunes Priscilla C G PCG Basílio-de-Oliveira Carlos A CA Basílio-de-Oliveira Rodrigo P RP Geraldo Luiz H M LHM Fonseca Celina G CG Lima Flávia R S FRS Mohana-Borges Ronaldo R Silva Emiliana M EM Dos Santos Flávia B FB Oliveira Edson R A ERA Paes Marciano V MV

Scientific reports 20180627 1

Dengue is a mild flu-like arboviral illness caused by dengue virus (DENV) that occurs in tropical and subtropical countries. An increasing number of reports have been indicating that dengue is also associated to neurological manifestations, however, little is known regarding the neuropathogenesis of the disease. Here, using BALB/c mice intravenously infected with DENV-2 strain 66985, we demonstrated that the virus is capable of invading and damaging the host's central nervous system (CNS). Brain ...[more]

PMID: 29950590

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Project description:BackgroundEnterovirus (EV) infection has been a serious health issue in Asia-Pacific region. It has been indicated that the occurrence of fatal hand foot and mouth disease (HFMD) cases following EV71 infection is mainly attributed to pulmonary edema. However, the development of pulmonary disorders after EV71 infection remains largely unknown. To establish an EV71-infected animal model and further explore the underlying association of central nervous system (CNS) invasion with pulmonary edema, we isolated a clinical source EV71 strain (ZZ1350) from a severe case in Henan Province.MethodsWe evaluated the cytotoxicity of ZZ1350 strain and the susceptibility in 3-day-old BALB/c mice with intraperitoneal, intracerebral and intramuscular inoculation. Various histopathological and immunohistochemical techniques were applied to determine the target organs or tissue damage after infection. Correlation analysis was used to identify the relationship between CNS injury and pulmonary disorders.ResultsOur experimental results suggested that ZZ1350 (C4 subtype) had high cytotoxicity against African green monkey kidney (Vero) cells and human rhabdomyosarcoma (RD) cells and neonatal BALB/c mice were highly susceptible to the infection with ZZ1350 through three different inoculation routes (2 × 106 pfu/mouse) exhibiting severe neurological and respiratory symptoms that were similar to clinical observation. Viral replication was found in brain, spinal cord, skeletal muscle, lung, spleen, liver, heart of infected mice and these sections also showed histopathological changes. We found that brain histology score was positive correlated with lung histology score in total experimental mice and mice under the three inoculation routes (P < 0.05). At the same time, there were positive correlations between spinal cord score and lung score in total experimental mice and mice with intracerebral inoculation (P < 0.05).ConclusionsZZ1350 strain is effective to establish animal model of EV71 infection with severe neurological and respiratory symptoms. The development of pulmonary disorders after EV71 infection is associated with severity of CNS damage.

Dataset Information

BALB/c mice infected with DENV-2 strain 66985 by the intravenous route display injury in the central nervous system.

Publications

BALB/c mice infected with DENV-2 strain 66985 by the intravenous route display injury in the central nervous system.

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