Abstract
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.
Highlights
Zika virus (ZIKV) and dengue virus (DENV) co-circulated during latest outbreaks in Brazil, it is important to evaluate the host cross-reactive immune responses to these viruses
Thirteen patients (76.5%) had dengue during their lifetime, presumed by the positivity for DENV IgG, in which 5 individuals were from DENV group, 3 from ZIKV, and 5 from DENV/ZIKV coinfection group
We detected a significant increase in total IFNgþCD8þ T cells frequency in cells (f) was exhibited in counter plots from one representative exposed donor, DENV, ZIKV, and DENV/ZIKV-patients by flow cytometry for both conditions
Summary
Zika virus (ZIKV) and dengue virus (DENV) co-circulated during latest outbreaks in Brazil, it is important to evaluate the host cross-reactive immune responses to these viruses. We evaluated chemokine receptors expression and single/multifunctional frequencies of IFNg, TNF, and IL2-producing T cells during these infections. Dengue virus (DENV) and Zika virus (ZIKV) belong to Flaviviridae family and both diseases affect significantly human health. These viruses are mainly transmitted by Aedes aegypti or albopictus infected mosquitoes. Human T lymphocyte responses to DENV and ZIKV infections and ZIKV, like other flaviviruses, are single-stranded, positive-sense RNA viruses with a genome of 10.7 kb and two flanking non-coding regions (50 NCR and 30 NCR). The four DENV serotypes share approximately 70% amino acid identity with each other, while ZIKV displays an overall 43% homology with DENV (with up to 68% identity for more conserved non-structural proteins) [1]
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