Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection.
<h4>Background</h4>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 seve...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-10-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://doi.org/10.1371/journal.pntd.0006540 |
| _version_ | 1818726293289566208 |
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| author | Dulharie T Wijeratne Samitha Fernando Laksiri Gomes Chandima Jeewandara Anushka Ginneliya Supun Samarasekara Ananda Wijewickrama Clare S Hardman Graham S Ogg Gathsaurie Neelika Malavige |
| author_facet | Dulharie T Wijeratne Samitha Fernando Laksiri Gomes Chandima Jeewandara Anushka Ginneliya Supun Samarasekara Ananda Wijewickrama Clare S Hardman Graham S Ogg Gathsaurie Neelika Malavige |
| author_sort | Dulharie T Wijeratne |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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 | 2024-12-17T21:55:54Z |
| format | Article |
| id | doaj.art-4500cf6fd9a143fda51366419196ad32 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-17T21:55:54Z |
| publishDate | 2018-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-4500cf6fd9a143fda51366419196ad322022-12-21T21:31:07ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352018-10-011210e000654010.1371/journal.pntd.0006540Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection.Dulharie T WijeratneSamitha FernandoLaksiri GomesChandima JeewandaraAnushka GinneliyaSupun SamarasekaraAnanda WijewickramaClare S HardmanGraham S OggGathsaurie Neelika Malavige<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.https://doi.org/10.1371/journal.pntd.0006540 |
| spellingShingle | Dulharie T Wijeratne Samitha Fernando Laksiri Gomes Chandima Jeewandara Anushka Ginneliya Supun Samarasekara Ananda Wijewickrama Clare S Hardman Graham S Ogg Gathsaurie Neelika Malavige Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection. PLoS Neglected Tropical Diseases |
| 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 |
| url | https://doi.org/10.1371/journal.pntd.0006540 |
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