title: Lethal Nipah virus infection induces rapid overexpression of CXCL10.
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.
authors.affiliation: Inserm U758, Human Virology, Ecole Normale Supérieure de Lyon, IFR128 BioSciences Lyon-Gerland Lyon-Sud, University of Lyon 1, Lyon, France.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Mathieu
authors.forename: Vanessa
authors.initials: V
authors.lastname: Guillaume
authors.forename: Amélie
authors.initials: A
authors.lastname: Sabine
authors.forename: Kien Chai
authors.initials: KC
authors.lastname: Ong
authors.forename: Kum Thong
authors.initials: KT
authors.lastname: Wong
authors.forename: Catherine
authors.initials: C
authors.lastname: Legras-Lachuer
authors.forename: Branka
authors.initials: B
authors.lastname: Horvat
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004660:Encephalitis / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation; D045464:Henipavirus Infections / Q000378:metabolism* / Q000401:mortality*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D007372:Interferons / Q000378:metabolism; D015233:Models, Statistical; D045405:Nipah Virus / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D012333:RNA, Messenger; D007372:Interferons