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Article ; Online: Current Understanding of the Role of T Cells in Chikungunya, Dengue and Zika Infections.

Mapalagamage, Maheshi / Weiskopf, Daniela / Sette, Alessandro / De Silva, Aruna Dharshan

2022 Volume 14, Issue 2

Abstract: Arboviral infections such as Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) are a major disease burden in tropical and sub-tropical countries, and there are no effective vaccinations or therapeutic drugs available at this time. Understanding the role ...

Abstract	Arboviral infections such as Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) are a major disease burden in tropical and sub-tropical countries, and there are no effective vaccinations or therapeutic drugs available at this time. Understanding the role of the T cell response is very important when designing effective vaccines. Currently, comprehensive identification of T cell epitopes during a DENV infection shows that CD8 and CD4 T cells and their specific phenotypes play protective and pathogenic roles. The protective role of CD8 T cells in DENV is carried out through the killing of infected cells and the production of proinflammatory cytokines, as CD4 T cells enhance B cell and CD8 T cell activities. A limited number of studies attempted to identify the involvement of T cells in CHIKV and ZIKV infection. The identification of human immunodominant ZIKV viral epitopes responsive to specific T cells is scarce, and none have been identified for CHIKV. In CHIKV infection, CD8 T cells are activated during the acute phase in the lymph nodes/blood, and CD4 T cells are activated during the chronic phase in the joints/muscles. Studies on the role of T cells in ZIKV-neuropathogenesis are limited and need to be explored. Many studies have shown the modulating actions of T cells due to cross-reactivity between DENV-ZIKV co-infections and have repeated heterologous/homologous DENV infection, which is an important factor to consider when developing an effective vaccine.
MeSH term(s)	Animals ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Chikungunya Fever/immunology ; Chikungunya Fever/therapy ; Chikungunya virus/immunology ; Cross Reactions ; Dengue/immunology ; Dengue/therapy ; Dengue Virus/immunology ; Epitopes, T-Lymphocyte/immunology ; Humans ; T-Lymphocytes/immunology ; Vaccine Development ; Viral Vaccines ; Zika Virus/immunology ; Zika Virus Infection/immunology ; Zika Virus Infection/therapy
Chemical Substances	Epitopes, T-Lymphocyte ; Viral Vaccines
Language	English
Publishing date	2022-01-25
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14020242
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Current Understanding of the Role of T Cells in Chikungunya, Dengue and Zika Infections

Mapalagamage, Maheshi / Weiskopf, Daniela / Sette, Alessandro / De Silva, Aruna Dharshan

Viruses. 2022 Jan. 25, v. 14, no. 2

2022

Abstract	Arboviral infections such as Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) are a major disease burden in tropical and sub-tropical countries, and there are no effective vaccinations or therapeutic drugs available at this time. Understanding the role of the T cell response is very important when designing effective vaccines. Currently, comprehensive identification of T cell epitopes during a DENV infection shows that CD8 and CD4 T cells and their specific phenotypes play protective and pathogenic roles. The protective role of CD8 T cells in DENV is carried out through the killing of infected cells and the production of proinflammatory cytokines, as CD4 T cells enhance B cell and CD8 T cell activities. A limited number of studies attempted to identify the involvement of T cells in CHIKV and ZIKV infection. The identification of human immunodominant ZIKV viral epitopes responsive to specific T cells is scarce, and none have been identified for CHIKV. In CHIKV infection, CD8 T cells are activated during the acute phase in the lymph nodes/blood, and CD4 T cells are activated during the chronic phase in the joints/muscles. Studies on the role of T cells in ZIKV-neuropathogenesis are limited and need to be explored. Many studies have shown the modulating actions of T cells due to cross-reactivity between DENV-ZIKV co-infections and have repeated heterologous/homologous DENV infection, which is an important factor to consider when developing an effective vaccine.
Keywords	B-lymphocytes ; CD8-positive T-lymphocytes ; burden of disease ; cross reaction ; cytokines ; dengue ; epitopes ; humans ; lymph ; protective effect ; vaccines
Language	English
Dates of publication	2022-0125
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14020242
Database	NAL-Catalogue (AGRICOLA)

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Article: Serological Evidence of

Abeygoonawardena, Harshi / Wijesinghe, Namal / Navaratne, Varuna / Balasuriya, Aindralal / Nguyen, Thi Thanh Ngan / Moi, Meng Ling / De Silva, Aruna Dharshan

Journal of global infectious diseases

2023 Volume 15, Issue 3, Page(s) 113–120

Abstract: Introduction: Arbovirus diseases remain a public health threat in Sri Lanka. Dengue is endemic and two outbreaks of chikungunya infections have been reported. There is limited data on Zika virus (ZIKV) infections in Sri Lanka, and this could be due to a ...

Abstract	Introduction: Arbovirus diseases remain a public health threat in Sri Lanka. Dengue is endemic and two outbreaks of chikungunya infections have been reported. There is limited data on Zika virus (ZIKV) infections in Sri Lanka, and this could be due to a lack of comprehensive ZIKV surveillance. Our aim was to determine the presence of antibodies to dengue, chikungunya, and Zika infections in adults from a suburban population in Sri Lanka. Methods: A total of 149 healthy adult volunteers over 18 years of age (mean age: 43±14 years, males - 43%), with no prior diagnosed arboviral infections and no history of overseas travel, participated in the study. ELISA and neutralization assays were carried out to detect past dengue, chikungunya, or Zika infections. Results: A total of 94.6% (141/149) of the participants demonstrated dengue IgG antibodies, 37.5% (56/149) were positive for chikungunya IgG, and 5.3% (8/149) were positive for anti-ZIKV IgG antibodies. Neutralization assays confirmed ZIKV-specific antibodies in 6.7% (10/149), when 40/149 of the participating population were tested. Conclusion: This clearly demonstrated past ZIKV infections in this population. In addition, this study indicates that >90% of individuals had asymptomatic dengue but no serious symptoms. These results provide a cross-sectional view on the DENV, ZIKV, and CHIKV epidemic status and demonstrate a need for the implementation of enhanced surveillance and more effective measures against the spread of these arbovirus diseases.
Language	English
Publishing date	2023-08-30
Publishing country	India
Document type	Journal Article
ZDB-ID	2545454-7
ISSN	0974-8245 ; 0974-777X
ISSN (online)	0974-8245
ISSN	0974-777X
DOI	10.4103/jgid.jgid_195_22
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Melioidosis in Sri Lanka.

Corea, Enoka M / de Silva, Aruna Dharshan / Thevanesam, Vasanthi

Tropical medicine and infectious disease

2018 Volume 3, Issue 1

Abstract: Until recently, Sri Lanka was not considered a country with endemic melioidosis. However, an increasing number of cases is being reported. National surveillance for melioidosis was instituted after 2008. A total of 250 culture-positive cases was recorded ...

Abstract	Until recently, Sri Lanka was not considered a country with endemic melioidosis. However, an increasing number of cases is being reported. National surveillance for melioidosis was instituted after 2008. A total of 250 culture-positive cases was recorded between 2006 and May 2017. Males predominated (71.6%). The age range was wide (2⁻92 years) reflecting a ubiquity of exposure. The majority (201/250, 80%) lived in rural areas. All provinces were affected. Case load increased during the two monsoonal periods (67%). There was representation of every population group including farmers (
Language	English
Publishing date	2018-02-21
Publishing country	Switzerland
Document type	Journal Article
ISSN	2414-6366
ISSN (online)	2414-6366
DOI	10.3390/tropicalmed3010022
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: A Population of CD4+CD8+ Double-Positive T Cells Associated with Risk of Plasma Leakage in Dengue Viral Infection

Yu, Esther Dawen / Wang, Hao / da Silva Antunes, Ricardo / Tian, Yuan / Tippalagama, Rashmi / Alahakoon, Shakila U. / Premawansa, Gayani / Wijewickrama, Ananda / Premawansa, Sunil / De Silva, Aruna Dharshan / Frazier, April / Grifoni, Alba / Sette, Alessandro / Weiskopf, Daniela

Viruses. 2022 Jan. 05, v. 14, no. 1

2022

Abstract: According to the WHO 2009 classification, dengue with warning signs is at the risk of developing severe form of dengue disease. One of the most important warning signs is plasma leakage, which can be a serious complication associated with higher ... ...

Abstract	According to the WHO 2009 classification, dengue with warning signs is at the risk of developing severe form of dengue disease. One of the most important warning signs is plasma leakage, which can be a serious complication associated with higher morbidity and mortality. We report that the frequency of CD4⁺CD8⁺ double-positive (DP) T cells is significantly increased in patients at risk of developing plasma leakage. Transcriptomic analysis demonstrated that CD4⁺CD8⁺ DP cells were distinct from CD4⁺ Single Positive (SP) T cells but co-clustered with CD8⁺ SP cells, indicating a largely similar transcriptional profile. Twenty significant differentially expressed (DE) genes were identified between CD4⁺CD8⁺ DP and CD8⁺ SP cells. These genes encode OX40 and CCR4 proteins as well as other molecules associated with cell signaling on the cell surface (NT5E, MXRA8, and PTPRK). While comparing the profile of gene expression in CD4⁺CD8⁺ DP cells from patients with and without warning signs of plasma leakage, similar expression profile was observed, implying a role of CD4⁺CD8⁺ DP cells in plasma leakage through a quantitative increase rather than functional alteration. This study provided novel insight into the host immune response during the acute febrile phase of DENV infection and the role of CD4⁺CD8⁺ DP T cells in the pathogenesis of plasma leakage.
Keywords	dengue ; gene expression ; immune response ; morbidity ; mortality ; pathogenesis ; risk ; transcription (genetics) ; transcriptomics
Language	English
Dates of publication	2022-0105
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14010090
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: An increase in p62/NBR1 levels in melioidosis patients of Sri Lanka exhibit a characteristic of potential host biomarker.

Saikh, Kamal U / Ranji, Cyra M / Ulrich, Robert G / Corea, Enoka / De Silva, Aruna Dharshan / Natesan, Mohan

Journal of medical microbiology

2020 Volume 69, Issue 10, Page(s) 1240–1248

Abstract: Introduction. ...

Abstract	Introduction.
MeSH term(s)	Adult ; Autophagy/physiology ; Biomarkers/metabolism ; Burkholderia pseudomallei/metabolism ; Female ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Leukocytes, Mononuclear/metabolism ; Male ; Melioidosis/metabolism ; Melioidosis/microbiology ; RNA-Binding Proteins/metabolism ; Sri Lanka
Chemical Substances	Biomarkers ; Intracellular Signaling Peptides and Proteins ; NBR1 protein, human ; P62 protein, human ; RNA-Binding Proteins
Language	English
Publishing date	2020-08-20
Publishing country	England
Document type	Journal Article
ZDB-ID	218356-0
ISSN	1473-5644 ; 0022-2615
ISSN (online)	1473-5644
ISSN	0022-2615
DOI	10.1099/jmm.0.001242
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Host gene expression analysis in Sri Lankan melioidosis patients.

Krishnananthasivam, Shivankari / Jayathilaka, Nimanthi / Sathkumara, Harindra Darshana / Corea, Enoka / Natesan, Mohan / De Silva, Aruna Dharshan

PLoS neglected tropical diseases

2017 Volume 11, Issue 6, Page(s) e0005643

Abstract: Background: Melioidosis is a life threatening infectious disease caused by the gram-negative bacillus Burkholderia pseudomallei predominantly found in southeast Asia and northern Australia. Studying the host transcription profiles in response to ... ...

Abstract	Background: Melioidosis is a life threatening infectious disease caused by the gram-negative bacillus Burkholderia pseudomallei predominantly found in southeast Asia and northern Australia. Studying the host transcription profiles in response to infection is crucial for understanding disease pathogenesis and correlates of disease severity, which may help improve therapeutic intervention and survival. The aim of this study was to analyze gene expression levels of human host factors in melioidosis patients and establish useful correlation with disease biomarkers, compared to healthy individuals and patients with sepsis caused by other pathogens. Methods: The study population consisted of 30 melioidosis cases, 10 healthy controls and 10 sepsis cases caused by other pathogens. Total RNA was extracted from peripheral blood mononuclear cells (PBMC's) of study subjects. Gene expression profiles of 25 gene targets including 19 immune response genes and 6 epigenetic factors were analyzed by real time quantitative polymerase chain reaction (RT-qPCR). Principal findings: Inflammatory response genes; TLR4, late onset inflammatory mediator HMGB1, genes associated with antigen presentation; MICB, PSMB2, PSMB8, PSME2, epigenetic regulators; DNMT3B, HDAC1, HDAC2 were significantly down regulated, whereas the anti-inflammatory gene; IL4 was up regulated in melioidosis patients compared to sepsis cases caused by other pathogens. Septicaemic melioidosis cases showed significant down regulation of IL8 compared to sepsis cases caused by other pathogens. HMGB1, MICB, PSMB8, PSMB2, PSME2, HDAC1, HDAC2 and DNMT3B showed consistent down regulation of gene expression in melioidosis patients compared to other sepsis infection, irrespective of comorbidities such as diabetes, duration of clinical symptoms and antibiotic treatment. Significance: Specific immune response genes and epigenetic regulators are differentially expressed among melioidosis patients and patients with sepsis caused by other pathogens. Therefore, these genes may serve as biomarkers for disease diagnosis to distinguish melioidosis from cases of sepsis due to other infections and therapeutic intervention for melioidosis.
MeSH term(s)	Biomarkers/analysis ; Diagnosis, Differential ; Gene Expression Profiling ; Genes, Regulator ; Humans ; Immunologic Factors/genetics ; Melioidosis/diagnosis ; Melioidosis/pathology ; Real-Time Polymerase Chain Reaction ; Sri Lanka
Chemical Substances	Biomarkers ; Immunologic Factors
Language	English
Publishing date	2017-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0005643
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Gene Expression Profile of Human Cytokines in Response to

Krishnananthasivam, Shivankari / Sathkumara, Harindra Darshana / Corea, Enoka / Natesan, Mohan / De Silva, Aruna Dharshan

mSphere

2017 Volume 2, Issue 2

Abstract: Melioidosis is an underreported infectious disease, caused by the Gram-negative ... ...

Abstract	Melioidosis is an underreported infectious disease, caused by the Gram-negative bacterium
Language	English
Publishing date	2017-03
Publishing country	United States
Document type	Journal Article
ISSN	2379-5042
ISSN	2379-5042
DOI	10.1128/mSphere.00121-17
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A Population of CD4

Yu, Esther Dawen / Wang, Hao / da Silva Antunes, Ricardo / Tian, Yuan / Tippalagama, Rashmi / Alahakoon, Shakila U / Premawansa, Gayani / Wijewickrama, Ananda / Premawansa, Sunil / De Silva, Aruna Dharshan / Frazier, April / Grifoni, Alba / Sette, Alessandro / Weiskopf, Daniela

Viruses

2022 Volume 14, Issue 1

Abstract	According to the WHO 2009 classification, dengue with warning signs is at the risk of developing severe form of dengue disease. One of the most important warning signs is plasma leakage, which can be a serious complication associated with higher morbidity and mortality. We report that the frequency of CD4
MeSH term(s)	Adult ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Dengue/blood ; Dengue/immunology ; Female ; Humans ; Lymphocyte Count ; Male ; Plasma ; Severe Dengue/blood ; Severe Dengue/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; Transcriptome ; Young Adult
Language	English
Publishing date	2022-01-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14010090
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Whole-Genome Sequences of Eight Clinical Isolates of Burkholderia pseudomallei from Melioidosis Patients in Eastern Sri Lanka.

Jayasinghearachchi, Himali S / Corea, Enoka M / Krishnananthasivam, Shivankari / Sathkumara, Harindra D / Francis, Vaithehi R / Abeysekere, Thimirangi R / De Silva, Aruna Dharshan

Microbiology resource announcements

2019 Volume 8, Issue 33

Abstract: Here, we report whole-genome sequences (WGS) of eight clinical isolates ... ...

Abstract	Here, we report whole-genome sequences (WGS) of eight clinical isolates of
Language	English
Publishing date	2019-08-15
Publishing country	United States
Document type	Journal Article
ISSN	2576-098X
ISSN (online)	2576-098X
DOI	10.1128/MRA.00645-19
Database	MEDical Literature Analysis and Retrieval System OnLINE

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