Abstract
Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10), an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.
Highlights
Nipah virus (NiV) is a recently emerged zoonotic pathogen of the family Paramyxoviridae that is distinguished by its ability to cause fatal disease in both animals and humans
Primary human endothelial cells are highly permissive to Nipah virus infection As endohelial cells are the first target of NiV infection, we have initially studied a permissivity of human umbilical vein endothelial cells (HUVECs) cultures to NiV
The inflammatory cellular infiltrates found in the central nervous system (CNS) of patients with acute NiV encephalitis include neutrophils, macrophages, lymphocytes and reactive microglia [7], which may all play an important role in NiV pathogenesis
Summary
Nipah virus (NiV) is a recently emerged zoonotic pathogen of the family Paramyxoviridae that is distinguished by its ability to cause fatal disease in both animals and humans. Since 1998 NiV has caused regular outbreaks, primarily in Bangladesh and India, with the most recent occurrences at the beginning of 2011 [3]. The endothelial cells represent one of the major targets of NiV infection, which is characterized by a systemic vasculitis and discrete parenchymal necrosis and inflammation in most organs, in the central nervous system (CNS). The high pathogenicity of NiV infection appears to be primarily due to endothelial damage, syncytia and vasculitis-induced thrombosis, ischemia and vascular microinfarction in the CNS, allowing the virus to overcome the blood-brain-barrier (BBB) and to subsequently infect neurons and glia cells in the brain parenchyma [2,7]
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