Human T cell responses to Japanese encephalitis virus in health and disease

Turtle, Lance and Bali, Tanushka and Buxton, Gemma and Chib, Savita and Chan, Sajesh and Soni, Mohammed and Hussain, Mohammed and Isenman, Heather and Fadnis, Prachi and Venkataswamy, Manjunatha M and Satishkumar, Vishali and Lewthwaite, Penny and Kurioka, Ayako and Krishna, Srinivasa and Shankar, Veera M and Ahmed, Riyaz and Begum, Ashia and Ravi, Vasanthapuram and Desai, Anita and Yoksan, Sutee and Fernandez, Stefan and Willberg, Christian B and Kloverpris, Henrik N and Conlon, Christopher and Klenerman, Paul and Satchidanandam, Vijaya and Solomon, Tom (2016) Human T cell responses to Japanese encephalitis virus in health and disease. In: JOURNAL OF EXPERIMENTAL MEDICINE, 213 (7). pp. 1331-1352.

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Abstract

Japanese encephalitis (JE) virus (JEV) is an important cause of encephalitis in children of South and Southeast Asia. However, the majority of individuals exposed to JEV only develop mild symptoms associated with long-lasting adaptive immunity. The related flavivirus dengue virus (DENV) cocirculates in many JEV-endemic areas, and clinical data suggest cross-protection between DENV and JEV. To address the role of T cell responses in protection against JEV, we conducted the first full-breadth analysis of the human memory T cell response using a synthetic peptide library. Ex vivo interferon-gamma (IFN-gamma) responses to JEV in healthy JEV-exposed donors were mostly CD8(+) and targeted nonstructural (NS) proteins, whereas IFN-gamma responses in recovered JE patients were mostly CD4(+) and targeted structural proteins and the secreted protein NS1. Among patients, a high quality, polyfunctional CD4(+) T cell response was associated with complete recovery from JE. T cell responses from healthy donors showed a high degree of cross-reactivity to DENV that was less apparent in recovered JE patients despite equal exposure. These data reveal divergent functional CD4(+) and CD8(+) T cell responses linked to different clinical outcomes of JEV infection, associated with distinct targeting and broad flavivirus cross-reactivity including epitopes from DENV, West Nile, and Zika virus.

Item Type:	Journal Article
Publication:	JOURNAL OF EXPERIMENTAL MEDICINE
Additional Information:	Copy right for this article belongs to the ROCKEFELLER UNIV PRESS, 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	08 Oct 2016 06:29
Last Modified:	08 Oct 2016 06:29
URI:	http://eprints.iisc.ac.in/id/eprint/54703

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