Inhibition of japanese encephalitis virus infection by flavivirus recombinant e protein domain III
- 395 Downloads
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus closely related to the human pathogens including yellow fever virus, dengue virus and West Nile virus. There are currently no effective antiviral therapies for all of the flavivirus and only a few highly effective vaccines are licensed for human use. In this paper, the E protein domain III (DIII) of six heterologous flaviviruses (DENV1-4, WNV and JEV) was expressed in Escherichia coli successfully. The proteins were purified after a solubilization and refolding procedure, characterized by SDS-PAGE and Western blotting. Competitive inhibition showed that all recombinant flavivirus DIII proteins blocked the entry of JEV into BHK-21 cells. Further studies indicated that antibodies induced by the soluble recombinant flavivirus DIII partially protected mice against lethal JEV challenge. These results demonstrated that recombinant flavivirus DIII proteins could inhibit JEV infection competitively, and immunization with proper folding flavivirus DIII induced cross-protection against JEV infection in mice, implying a possible role of DIII for the cross-protection among flavivirus as well as its use in antigens for immunization in animal models.
KeywordsJapanese encephalitis virus E protein domain III Cross-protection Antibody
Unable to display preview. Download preview PDF.
- Eder S, Dubischar-Kastner K, Firbas C, Jelinek T, Jilma B, Kaltenboeck A, Knappik M, Kollaritsch H, Kundi M, Paulke-Korinek M, Schuller E, and Klade C S. 2011. Long term immunity following a booster dose of the inactivated Japanese Encephalitis vaccine IXIARO (R), IC51. Vaccine, 29: 2607–2612.PubMedCrossRefGoogle Scholar
- Ghosh D, and Basu A. 2009. Japanese Encephalitis — A Pathological and Clinical Perspective. Plos Neglected Tropical Diseases, 3.Google Scholar
- Lindenbach B D, H. J. Thiel, and C. M. Rice. 2007. Flaviviridae: the virus and their replication. In Howley D M K a P M (ed.), Fields virology, 5th ed, vol. 1, Lippincott-Raven, Philadelphia, Pa.Google Scholar
- Lozach P Y, Burleigh L, Staropoli I, Navarro-Sanchez E, Harriague J, Virelizier J L, Rey F A, Despres P, Arenzana-Seisdedos F, and Amara A. 2005. Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN)-mediated enhancement of dengue virus infection is independent of DC-SIGN internalization signals. J Biol Chem, 280: 23698–23708.PubMedCrossRefGoogle Scholar
- Schioler K L, Samuel M, and Wai K L. 2007. Vaccines for preventing Japanese encephalitis. Cochrane Database Syst Rev: CD004263.Google Scholar
- Wu K P, Wu C W, Tsao Y P, Kuo T W, Lou Y C, Lin C W, Wu S C, and Cheng J W. 2003. Structural basis of a flavivirus recognized by its neutralizing antibody — Solution structure of the domain III of the Japanese encephalitis virus envelope protein. Journal of Biological Chemistry, 278: 46007–46013.PubMedCrossRefGoogle Scholar
- Zaitseva E, Yang S T, Melikov K, Pourmal S, and Chernomordik L V. 2010. Dengue Virus Ensures Its Fusion in Late Endosomes Using Compartment-Specific Lipids. PLoS Pathog, 6.Google Scholar