Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection
<strong>Background</strong> 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 var...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Public Library of Science
2018
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| _version_ | 1797104373748203520 |
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| author | Wijeratne, DT Fernando, S Gomes, L Jeewandara, C Ginneliya, A Samarasekara, S Wijewickrama, A Hardman, CS Ogg, GS Malavige, GN |
| author_facet | Wijeratne, DT Fernando, S Gomes, L Jeewandara, C Ginneliya, A Samarasekara, S Wijewickrama, A Hardman, CS Ogg, GS Malavige, GN |
| author_sort | Wijeratne, DT |
| collection | OXFORD |
| description | <strong>Background</strong> 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. <strong>Methodology/Principal findings</strong> Using ex vivo IFNγ 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. <strong>Conclusions/Significance</strong> Early appearance of DENV-specific T cell IFNγ 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. |
| first_indexed | 2024-03-07T06:32:56Z |
| format | Journal article |
| id | oxford-uuid:f6a2d52e-8a54-4b02-b0cb-3ab97a2b24d2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:32:56Z |
| publishDate | 2018 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:f6a2d52e-8a54-4b02-b0cb-3ab97a2b24d22022-03-27T12:36:31ZQuantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f6a2d52e-8a54-4b02-b0cb-3ab97a2b24d2EnglishSymplectic Elements at OxfordPublic Library of Science2018Wijeratne, DTFernando, SGomes, LJeewandara, CGinneliya, ASamarasekara, SWijewickrama, AHardman, CSOgg, GSMalavige, GN<strong>Background</strong> 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. <strong>Methodology/Principal findings</strong> Using ex vivo IFNγ 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. <strong>Conclusions/Significance</strong> Early appearance of DENV-specific T cell IFNγ 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. |
| spellingShingle | Wijeratne, DT Fernando, S Gomes, L Jeewandara, C Ginneliya, A Samarasekara, S Wijewickrama, A Hardman, CS Ogg, GS Malavige, GN Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection |
| title | Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection |
| title_full | Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection |
| title_fullStr | Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection |
| title_full_unstemmed | Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection |
| title_short | Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection |
| title_sort | quantification of dengue virus specific t cell responses and correlation with viral load and clinical disease severity in acute dengue infection |
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