Silencing early viral replication in macrophages and dendritic cells effectively suppresses flavivirus encephalitis.

作者: Chunting Ye , Sojan Abraham , Haoquan Wu , Premlata Shankar , N. Manjunath

DOI: 10.1371/JOURNAL.PONE.0017889

关键词:

摘要: West Nile (WN) and St. Louis encephalitis (SLE) viruses can cause fatal neurological infection currently there is neither a specific treatment nor an approved vaccine for these infections. In our earlier studies, we have reported that siRNAs be developed as broad-spectrum antivirals the of caused by related small peptide called RVG-9R deliver siRNA to neuronal cells well macrophages. To increase repertoire antiflaviviral siRNAs, screened 25 targeting conserved regions in viral genome. Five were found inhibit both WNV SLE replication vitro reflecting antiviral activity one was also validated vivo. addition, show delivers macrophages dendritic cells, resulting effective suppression virus replication. Mice challenged intraperitoneally (i.p.) with (WNV) treated i.v. siRNA/peptide complex. The peritoneal isolated on day 3 post transferred new hosts. receiving from anti-viral mice failed develop any disease while control irrelevant all died encephalitis. These studies suggest early RVG-9R-mediated delivery key preventing development disease.

参考文章(22)
Michael S. Diamond, Bimmi Shrestha, Erin Mehlhop, Elizabeth Sitati, Michael Engle, Innate and Adaptive Immune Responses Determine Protection against Disseminated Infection by West Nile Encephalitis Virus Viral Immunology. ,vol. 16, pp. 259- 278 ,(2003) , 10.1089/088282403322396082
Brad J Biggerstaff, Lyle R Petersen, None, Estimated risk of transmission of the West Nile virus through blood transfusion in the US, 2002. Transfusion. ,vol. 43, pp. 1007- 1017 ,(2003) , 10.1046/J.1537-2995.2003.00480.X
N. Manjunath, Priti Kumar, Sang Kyung Lee, Premlata Shankar, Interfering antiviral immunity: application, subversion, hope? Trends in Immunology. ,vol. 27, pp. 328- 335 ,(2006) , 10.1016/J.IT.2006.05.006
Olivier ter Brake, Karen 't Hooft, Ying Poi Liu, Mireille Centlivre, Karin Jasmijn von Eije, Ben Berkhout, Lentiviral Vector Design for Multiple shRNA Expression and Durable HIV-1 Inhibition Molecular Therapy. ,vol. 16, pp. 557- 564 ,(2008) , 10.1038/SJ.MT.6300382
Monica R. Lares, John J. Rossi, Dominique L. Ouellet, RNAi and small interfering RNAs in human disease therapeutic applications Trends in Biotechnology. ,vol. 28, pp. 570- 579 ,(2010) , 10.1016/J.TIBTECH.2010.07.009
Frank Kirchhoff, Silencing HIV-1 In Vivo. Cell. ,vol. 134, pp. 566- 568 ,(2008) , 10.1016/J.CELL.2008.08.004
Sang-Soo Kim, Chunting Ye, Priti Kumar, Isaac Chiu, Sandesh Subramanya, Haoquan Wu, Premlata Shankar, N Manjunath, Targeted Delivery of siRNA to Macrophages for Anti-inflammatory Treatment Molecular Therapy. ,vol. 18, pp. 993- 1001 ,(2010) , 10.1038/MT.2010.27
N. Manjunath, Haoquan Wu, Sandesh Subramanya, Premlata Shankar, Lentiviral delivery of short hairpin RNAs Advanced Drug Delivery Reviews. ,vol. 61, pp. 732- 745 ,(2009) , 10.1016/J.ADDR.2009.03.004
Kenneth L. Tyler, West Nile Virus Infection in the United States Archives of Neurology. ,vol. 61, pp. 1190- 1195 ,(2004) , 10.1001/ARCHNEUR.61.8.1190