Background In order to understand the role of dengue virus (DENV) specific T cell responses that associate with protection, we studied their frequency and phenotype in relation to clinical disease severity and resolution of viraemia in a large cohort of patients with varying severity of acute dengue infection. Methodology/Principal findings Using ex vivo IFN gamma ELISpot assays we determined the frequency of dengue viral peptide (DENV)-NS3, NS1 and NS5 responsive T cells in 74 adult patients with acute dengue infection and examined the association of responsive T cell frequency with the extent of viraemia and clinical disease severity. We found that total DENV-specific and DENV-NS3-specific T cell responses, were higher in patients with dengue fever (DF), when compared to those with dengue haemorrhagic fever (DHF). In addition, those with DF had significantly higher (p = 0.02) DENV-specific T cell responses on day 4 of infection compared to those who subsequently developed DHF. DENV peptide specific T cell responses inversely correlated with the degree of viraemia, which was most significant for DENV-NS3 specific T cell responses (Spearman's r = -0.47, p = 0.0003). The frequency of T cell responses to NS1, NS5 and pooled DENV peptides, correlated with the degree of thrombocytopenia but had no association with levels of liver transaminases. In contrast, total DENV-IgG inversely correlated with the degree of thrombocytopenia and levels of liver transaminases. Conclusions/Significance Early appearance of DENV-specific T cell IFN gamma responses before the onset of plasma leakage, appears to associate with milder clinical disease and resolution of viraemia, suggesting a protective role in acute dengue infection.

Flavivirus is a genus of the family Flaviviridae. It includes West Nile virus (WNV), dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), and several other viruses which lead to extensive morbidity and mortality in humans. To establish infection and replication in the hosts, flaviviruses have evolved a variety of strategies to modulate the host's immune responses. In this review, the strategies employed by flaviviruses to evade the innate and adaptive immunity of host are summarized based on current studies, with a major focus on the inhibition of interferon, complement, natural killer (NK) cell, B cell, and T cell responses. This review aims to provide an overview of the current understanding for the mechanisms used by flaviviruses to escape the host's immune response, which will facilitate the future studies on flavivirus pathogenesis and the development of anti-flavivirus therapeutics. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.