Strong CD4 T Cell Responses to Zika Virus Antigens in a Cohort of Dengue Virus Immune Mothers of Congenital Zika Virus Syndrome Infants
Background: There is an urgent need to understand the complex relationship between cross-reactive anti-viral immunity, disease susceptibility, and severity in the face of differential exposure to related, circulating Flaviviruses. Co-exposure to Dengue virus and Zika virus in Brazil is a case in poi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00185/full |
| _version_ | 1819174829725581312 |
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| author | Catherine J. Reynolds Patricia Watber Camilla Natália Oliveira Santos Danielle Rodrigues Ribeiro Juliana Cardoso Alves Adriana B. L. Fonseca Ana J. B. Bispo Roseane L. S. Porto Kalliopi Bokea Amélia Maria Ribeiro de Jesus Roque Pacheco de Almeida Rosemary J. Boyton Daniel M. Altmann |
| author_facet | Catherine J. Reynolds Patricia Watber Camilla Natália Oliveira Santos Danielle Rodrigues Ribeiro Juliana Cardoso Alves Adriana B. L. Fonseca Ana J. B. Bispo Roseane L. S. Porto Kalliopi Bokea Amélia Maria Ribeiro de Jesus Roque Pacheco de Almeida Rosemary J. Boyton Daniel M. Altmann |
| author_sort | Catherine J. Reynolds |
| collection | DOAJ |
| description | Background: There is an urgent need to understand the complex relationship between cross-reactive anti-viral immunity, disease susceptibility, and severity in the face of differential exposure to related, circulating Flaviviruses. Co-exposure to Dengue virus and Zika virus in Brazil is a case in point. A devastating aspect of the 2015–2016 South American Zika outbreak was the dramatic increase in numbers of infants born with microcephaly to mothers exposed to Zika virus during pregnancy. It has been proposed that this is more likely to ensue from Zika infection in women lacking cross-protective Dengue immunity. In this case series we measure the prevalence of Dengue immunity in a cohort of mothers exposed to Zika virus during pregnancy in the 2015–2016 Zika outbreak that gave birth to an infant affected by microcephaly and explore their adaptive immunity to Zika virus.Results: Fifty women from Sergipe, Brazil who gave birth to infants with microcephaly following Zika virus exposure during the 2015–16 outbreak were tested for serological evidence of Dengue exposure and IFNγ ELISpot spot forming cell (SFC) response to Zika virus. The majority (46/50) demonstrated Dengue immunity. IFNγ ELISpot responses to Zika virus antigens showed the following hierarchy: Env>NS1>NS3>C protein. Twenty T cell epitopes from Zika virus Env were identified. Responses to Zika virus antigens Env and NS1 were polyfunctional with cells making IFNγ, TNFα, IL-4, IL-13, and IL-10. In contrast, responses to NS5 only produced the immune regulatory TGFβ1 cytokine. There were SFC responses against Zika virus Env (1-20) and variant peptide sequences from West Nile virus, Dengue virus 1–4 and Yellow Fever virus.Conclusion: Almost all the women in our study showed serological evidence of Dengue immunity, suggesting that microcephaly can occur in DENV immune mothers. T cell immunity to Zika virus showed a multifunctional response to the antigens Env and NS1 and immune regulatory responses to NS5 and C protein. Our data support an argument that different viral products may skew the antiviral response to a more pro or anti-inflammatory outcome, with an associated impact on immunopathogenesis. |
| first_indexed | 2024-12-22T20:45:12Z |
| format | Article |
| id | doaj.art-296af5ca765e46f892b6c8f4050b8a0c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T20:45:12Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-296af5ca765e46f892b6c8f4050b8a0c2022-12-21T18:13:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-02-011110.3389/fimmu.2020.00185474308Strong CD4 T Cell Responses to Zika Virus Antigens in a Cohort of Dengue Virus Immune Mothers of Congenital Zika Virus Syndrome InfantsCatherine J. Reynolds0Patricia Watber1Camilla Natália Oliveira Santos2Danielle Rodrigues Ribeiro3Juliana Cardoso Alves4Adriana B. L. Fonseca5Ana J. B. Bispo6Roseane L. S. Porto7Kalliopi Bokea8Amélia Maria Ribeiro de Jesus9Roque Pacheco de Almeida10Rosemary J. Boyton11Daniel M. Altmann12Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United KingdomDepartment of Infectious Disease, Faculty of Medicine, Imperial College London, London, United KingdomMolecular Biology Laboratory, Graduate Program in Health Science, University Hospital of the Federal University of Sergipe, Aracaju, BrazilMolecular Biology Laboratory, Graduate Program in Health Science, University Hospital of the Federal University of Sergipe, Aracaju, BrazilMolecular Biology Laboratory, Graduate Program in Health Science, University Hospital of the Federal University of Sergipe, Aracaju, BrazilMicrocephaly Clinic, Pediatric Division, University Hospital of the Federal University of Sergipe, Aracaju, BrazilMicrocephaly Clinic, Pediatric Division, University Hospital of the Federal University of Sergipe, Aracaju, BrazilMicrocephaly Clinic, Pediatric Division, University Hospital of the Federal University of Sergipe, Aracaju, BrazilDepartment of Infectious Disease, Faculty of Medicine, Imperial College London, London, United KingdomMolecular Biology Laboratory, Department of Medicine, University Hospital of the Federal University of Sergipe, Aracaju, BrazilMolecular Biology Laboratory, Department of Medicine, University Hospital of the Federal University of Sergipe, Aracaju, BrazilDepartment of Infectious Disease, Faculty of Medicine, Imperial College London, London, United KingdomDepartment of Immunology and Inflammation, Faculty of Medicine, Imperial College London, London, United KingdomBackground: There is an urgent need to understand the complex relationship between cross-reactive anti-viral immunity, disease susceptibility, and severity in the face of differential exposure to related, circulating Flaviviruses. Co-exposure to Dengue virus and Zika virus in Brazil is a case in point. A devastating aspect of the 2015–2016 South American Zika outbreak was the dramatic increase in numbers of infants born with microcephaly to mothers exposed to Zika virus during pregnancy. It has been proposed that this is more likely to ensue from Zika infection in women lacking cross-protective Dengue immunity. In this case series we measure the prevalence of Dengue immunity in a cohort of mothers exposed to Zika virus during pregnancy in the 2015–2016 Zika outbreak that gave birth to an infant affected by microcephaly and explore their adaptive immunity to Zika virus.Results: Fifty women from Sergipe, Brazil who gave birth to infants with microcephaly following Zika virus exposure during the 2015–16 outbreak were tested for serological evidence of Dengue exposure and IFNγ ELISpot spot forming cell (SFC) response to Zika virus. The majority (46/50) demonstrated Dengue immunity. IFNγ ELISpot responses to Zika virus antigens showed the following hierarchy: Env>NS1>NS3>C protein. Twenty T cell epitopes from Zika virus Env were identified. Responses to Zika virus antigens Env and NS1 were polyfunctional with cells making IFNγ, TNFα, IL-4, IL-13, and IL-10. In contrast, responses to NS5 only produced the immune regulatory TGFβ1 cytokine. There were SFC responses against Zika virus Env (1-20) and variant peptide sequences from West Nile virus, Dengue virus 1–4 and Yellow Fever virus.Conclusion: Almost all the women in our study showed serological evidence of Dengue immunity, suggesting that microcephaly can occur in DENV immune mothers. T cell immunity to Zika virus showed a multifunctional response to the antigens Env and NS1 and immune regulatory responses to NS5 and C protein. Our data support an argument that different viral products may skew the antiviral response to a more pro or anti-inflammatory outcome, with an associated impact on immunopathogenesis.https://www.frontiersin.org/article/10.3389/fimmu.2020.00185/fullzika virusdengue virusT cell epitopeflaviviruscross-reactivitymicrocephaly |
| spellingShingle | Catherine J. Reynolds Patricia Watber Camilla Natália Oliveira Santos Danielle Rodrigues Ribeiro Juliana Cardoso Alves Adriana B. L. Fonseca Ana J. B. Bispo Roseane L. S. Porto Kalliopi Bokea Amélia Maria Ribeiro de Jesus Roque Pacheco de Almeida Rosemary J. Boyton Daniel M. Altmann Strong CD4 T Cell Responses to Zika Virus Antigens in a Cohort of Dengue Virus Immune Mothers of Congenital Zika Virus Syndrome Infants Frontiers in Immunology zika virus dengue virus T cell epitope flavivirus cross-reactivity microcephaly |
| title | Strong CD4 T Cell Responses to Zika Virus Antigens in a Cohort of Dengue Virus Immune Mothers of Congenital Zika Virus Syndrome Infants |
| title_full | Strong CD4 T Cell Responses to Zika Virus Antigens in a Cohort of Dengue Virus Immune Mothers of Congenital Zika Virus Syndrome Infants |
| title_fullStr | Strong CD4 T Cell Responses to Zika Virus Antigens in a Cohort of Dengue Virus Immune Mothers of Congenital Zika Virus Syndrome Infants |
| title_full_unstemmed | Strong CD4 T Cell Responses to Zika Virus Antigens in a Cohort of Dengue Virus Immune Mothers of Congenital Zika Virus Syndrome Infants |
| title_short | Strong CD4 T Cell Responses to Zika Virus Antigens in a Cohort of Dengue Virus Immune Mothers of Congenital Zika Virus Syndrome Infants |
| title_sort | strong cd4 t cell responses to zika virus antigens in a cohort of dengue virus immune mothers of congenital zika virus syndrome infants |
| topic | zika virus dengue virus T cell epitope flavivirus cross-reactivity microcephaly |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00185/full |
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