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Journal of Virology, May 2009, p. 4766-4777, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.01850-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Virus-Specific Cytolytic Antibodies to Nonstructural Protein 1 of Japanese Encephalitis Virus Effect Reduction of Virus Output from Infected Cells{triangledown}

Venkatramana D. Krishna,1,2 Manjuladevi Rangappa,1 and Vijaya Satchidanandam1*

Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka 560012, India,1 Bhat Biotech India (P) Ltd., Bangalore, Karnataka 560100, India2

Received 3 September 2008/ Accepted 20 February 2009

We demonstrate the presence of nonstructural protein 1 (NS1)-specific antibodies in a significant proportion of convalescent-phase human serum samples obtained from a cohort in an area where Japanese encephalitis virus (JEV) is endemic. Sera containing antibodies to NS1 but not those with antibodies to other JEV proteins, such as envelope, brought about complement-mediated lysis of JEV-infected BHK-21 cells. Target cells infected with a recombinant poxvirus expressing JEV NS1 on the cell surface confirmed the NS1 specificity of cytolytic antibodies. Mouse anti-NS1 cytolytic sera caused a complement-dependent reduction in virus output from infected human cells, demonstrating their important role in viral control. Antibodies elicited by JEV NS1 did not cross lyse West Nile virus- or dengue virus-infected cells despite immunoprecipitating the NS1 proteins of these related flaviviruses. Additionally, JEV NS1 failed to bind complement factor H, in contrast to NS1 of West Nile virus, suggesting that the NS1 proteins of different flaviviruses have distinctly different mechanisms for interacting with the host. Our results also point to an important role for JEV NS1-specific human immune responses in protection against JE and provide a strong case for inclusion of the NS1 protein in next generation of JEV vaccines.

* Corresponding author. Mailing address: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka 560012, India. Phone: 91-80-22932685. Fax: 91-80-23602697. E-mail: vijaya{at}mcbl.iisc.ernet.in

{triangledown} Published ahead of print on 4 March 2009.

Journal of Virology, May 2009, p. 4766-4777, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.01850-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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