Dengue Virus Serotype-2 Impairs Proliferation of Healthy Donors' T Lymphocytes

Fuentes-Miranda, C J; Sánchez‐García, Francisco Javier; Çoker, Ahmet; Rojas-Espinosa, O; Salinas-Tobón, R; Moreno-Altamirano, María Maximina Bertha

doi:10.1159/000357180

Cited by 4 publications

(2 citation statements)

References 52 publications

(65 reference statements)

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“…In 2001, our group described a reduced frequency of CD4 + and CD8 + T lymphocytes and a poor ability for T‐lymphocyte proliferation in response to mitogens and dengue antigens in acute DENV‐infected patients, but re‐established in convalescence phase . Another study found that in vitro exposure to DENV‐2 of T lymphocytes isolated from healthy donors reduces the lymphoproliferative capacity in response to mitogen, suggesting that DENV‐2 can inhibit T cell‐mediated immunity, bypassing monocytes and dendritic cells, classical DENV cell targets .…”

Section: Discussionmentioning

confidence: 99%

Human T cell responses to Dengue and Zika virus infection compared to Dengue/Zika coinfection

Badolato-Corrêa

Sánchez‐Arcila

Souza

et al. 2017

Immunity Inflam & Disease

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IntroductionZika virus (ZIKV) and dengue virus (DENV) co‐circulated during latest outbreaks in Brazil, hence, it is important to evaluate the host cross‐reactive immune responses to these viruses. So far, little is known about human T cell responses to ZIKV and no reports detail adaptive immune responses during DENV/ZIKV coinfection.MethodsHere, we studied T cells responses in well‐characterized groups of DENV, ZIKV, or DENV/ZIKV infected patients and DENV‐exposed healthy donors. We evaluated chemokine receptors expression and single/multifunctional frequencies of IFNγ, TNF, and IL2‐producing T cells during these infections. Even without antigenic stimulation, it was possible to detect chemokine receptors and IFNγ, TNF, and IL2‐producing T cells from all individuals by flow cytometry. Additionally, PBMCs’ IFNγ response to DENV NS1 protein and to polyclonal stimuli was evaluated by ELISPOT.ResultsDENV and ZIKV infections and DENV/ZIKV coinfections similarly induced expression of CCR5, CX3CR1, and CXCR3 on CD4 and CD8 T cells. DENV/ZIKV coinfection decreased the ability of CD4+ T cells to produce IFNγ+, TNF+, TNF + IFNγ+, and TNF + IL2+, compared to DENV and ZIKV infections. A higher magnitude of IFNγ response to DENV NS1 was found in donors with a history of dengue infection, however, a hyporesponsiveness was found in acute DENV, ZIKV, or DENV/ZIKV infected patients, even previously infected with DENV.ConclusionTherefore, we emphasize the potential impact of coinfection on the immune response from human hosts, mainly in areas where DENV and ZIKV cocirculate.

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Section: Discussionmentioning

confidence: 99%

Human T cell responses to Dengue and Zika virus infection compared to Dengue/Zika coinfection

Badolato-Corrêa

Sánchez‐Arcila

Souza

et al. 2017

Immunity Inflam & Disease

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show abstract

“…T lymphocytes are not infected by dengue virus, nevertheless it is possible that exposure to virus and/or proteins viral may affect their function. T lymphocytes from DENV-infected individuals are impaired in their proliferative capacity, although this effect has been attributed to altered function of antigen-presenting cells rather than to an intrinsic defect on T lymphocytes [33]. The host immune responses have been considered as the major factor responsible for dengue pathogenesis, resulting in an altered immune response, which triggers T cell activation, and the release of cytokines and chemical mediators has been a risk factor in secondary Infection.…”

Section: Discussionmentioning

confidence: 99%

Differential humoral and cellular immunity induced by vaccination using plasmid DNA and protein recombinant expressing the NS3 protein of dengue virus type 3

et al. 2016

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BackgroundThe dengue non-structural 3 (NS3) is a multifunctional protein, containing a serine-protease domain, located at the N-terminal portion, and helicase, NTPase and RTPase domains present in the C-terminal region. This protein is considered the main target for CD4+ and CD8+ T cell responses during dengue infection, which may be involved in protection. However, few studies have been undertaken evaluating the use of this protein as a protective antigen against dengue, as well as other flavivirus. In the present work we evaluated the potential of the NS3 (protease domain) as a protective antigen by comparing the administration of a recombinant protein versus a DNA vaccine in the mouse model.ResultsBALB/c mice were immunized with the recombinant protein NS3-DEN3 via intraperitoneal and with plasmid pcDNA3/NS3-DEN3 intramuscularly and the immune response was evaluated. The activity of T lymphocytes was analyzed by the MTT assay, and cells of mice immunized with the recombinant protein showed no activity when stimulated with the homologous protein. However, cells from mice immunized with DNA, responded to stimulation with the recombinant protein. When the expression (RT-PCR) and cytokine production (ELISA) was evaluated in the splenocytes, different behavior depending on the type of immunization was observed, splenocytes of mice immunized with the recombinant protein expressed cytokines such as IL-4, IL-10 and produced high concentrations of IL-1, IL-6 and TNFα. Splenocytes from mice immunized with DNA expressed IL-2 and IFNγ and did not produce IL-6. In addition, immunization with the recombinant protein induced the production of antibodies that are detected up to a dilution 1:3200 by ELISA and Western blot assays, however, the serum of mice immunized with DNA presented no detectable antibody titers.ConclusionThe results obtained in this study show that administration of pcDNA3/NS3-DEN3 induces a favorable response in the activation of T lymphocytes with low production of specific antibodies against NS3-DEN3.

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Immunization of recombinant NS3 protein (protease region) of dengue virus induces high levels of CTLA-4 and apoptosis in splenocytes of BALB/c mice

Romero-Cruz,

Ramos-Ligonio,

García-Alejandro

et al. 2024

Virus Genes

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Dengue Virus Serotype-2 Impairs Proliferation of Healthy Donors' T Lymphocytes

Cited by 4 publications

References 52 publications

Human T cell responses to Dengue and Zika virus infection compared to Dengue/Zika coinfection

Human T cell responses to Dengue and Zika virus infection compared to Dengue/Zika coinfection

Differential humoral and cellular immunity induced by vaccination using plasmid DNA and protein recombinant expressing the NS3 protein of dengue virus type 3

Immunization of recombinant NS3 protein (protease region) of dengue virus induces high levels of CTLA-4 and apoptosis in splenocytes of BALB/c mice

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