distinct and overlapping roles of nipah virus p gene products in modulating the human endothelial cell antiviral response不同的尼帕病毒p基因产物和重叠的角色在调节人类内皮细胞抗病毒反应.pdfVIP

Distinct and Overlapping Roles of Nipah Virus P Gene Products in Modulating the Human Endothelial Cell Antiviral Response 1,2 3,4 2 1 2 Michael K. Lo *, Mark E. Peeples , William J. Bellini , Stuart T. Nichol , Paul A. Rota , Christina F. Spiropoulou1 1 Centers for Disease Control Prevention, Viral Special Pathogens Branch, Atlanta, Georgia, United States of America, 2 Centers for Disease Control and Prevention, Measles, Mumps, Rubella, and Herpes Virus Branch, Atlanta, Georgia, United States of America, 3 The Research Institute at the Nationwide Children’s Hospital, Columbus, Ohio, United States of America, 4 The Ohio State University, Department of Pediatrics, Columbus, Ohio, United States of America Abstract Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis in up to 75% of infected humans. Like other paramyxoviruses, NiV employs co-transcriptional mRNA editing during transcription of the phosphoprotein (P) gene to generate additional mRNAs encoding the V and W proteins. The C protein is translated from the P mRNA, but in an alternative reading frame. There is evidence from both in vitro and in vivo studies to show that the P gene products play a role in NiV pathogenesis. We have developed a reverse genetic system to dissect the individual roles of the NiV P gene products in limiting the antiviral response in primary human microvascular lung endothelial cells, which represent important targets in human NiV infection. By characterizing growth curves and early antiviral responses against a number of recombinant NiVs with genetic modifications altering expression of the proteins encoded by the P gene, we observed that multiple