Lethal Nipah virus infection induces rapid overexpression of CXCL10

• Published in: PloS one 2012-02, Vol.7 (2), p.e32157
• Main Authors: Mathieu, Cyrille, Guillaume, Vanessa, Sabine, Amélie, Ong, Kien Chai, Wong, Kum Thong, Legras-Lachuer, Catherine, Horvat, Branka
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Biological response modifiers; Biology; Brain; Cells, Cultured; Chemokine CXCL10; Chemokine CXCL10 - metabolism; Chemokines; Cricetinae; Cricetulus; CXCL10 protein; Encephalitis; Encephalitis - virology; Endothelial cells; Endothelium; Enzyme-Linked Immunosorbent Assay; Enzyme-Linked Immunosorbent Assay - methods; Epidemics; Gene expression; Gene Expression Regulation; Genes; Granulocytes; Hamsters; Henipavirus Infections; Henipavirus Infections - metabolism; Henipavirus Infections - mortality; Hepatitis; Human Umbilical Vein Endothelial Cells; Human Umbilical Vein Endothelial Cells - cytology; Humans; Immune response; Immune system; Immunization; Immunohistochemistry; Immunohistochemistry - methods; In vitro methods and tests; In vivo methods and tests; Infections; Inflammation; Interferon; Interferons; Interferons - metabolism; IP-10 protein; Kinetics; Life Sciences; Mathematical models; Medical research; Medicine; Models, Statistical; Neurons; Neurotoxicity; Nipah Virus; Nipah Virus - metabolism; Oligonucleotide Array Sequence Analysis; Organs; Outbreaks; Pathogenesis; Patients; Proteins; RNA; RNA, Messenger; RNA, Messenger - metabolism; Sequence Analysis, DNA; Time Factors; Umbilical vein; Veins & arteries; Viral infections; Virology; Virus diseases; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0032157

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.