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      Zika virus pathogenesis in rhesus macaques is unaffected by pre-existing immunity to dengue virus

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          Abstract

          Zika virus (ZIKV) is a re-emerging virus that has recently spread into dengue virus (DENV) endemic regions and cross-reactive antibodies (Abs) could potentially affect ZIKV pathogenesis. Using DENV-immune serum, it has been shown in vitro that antibody-dependent enhancement (ADE) of ZIKV infection can occur. Here we study the effects of pre-existing DENV immunity on ZIKV infection in vivo. We infect two cohorts of rhesus macaques with ZIKV; one cohort has been exposed to DENV 2.8 years earlier and a second control cohort is naïve to flaviviral infection. Our results, while confirming ADE in vitro, suggest that pre-existing DENV immunity does not result in more severe ZIKV disease. Rather our results show a reduction in the number of days of ZIKV viremia compared to naïve macaques and that the previous exposure to DENV may result in modulation of the immune response without resulting in enhancement of ZIKV pathogenesis.

          Abstract

          Antibodies against dengue virus (DENV) can increase Zika virus (ZIKV) infection in vitro, but their role in vivo remains largely unknown. Here, the authors show that pre-existing immunity from a 2.8 years earlier DENV infection does not affect ZIKV pathogenesis in macaques but instead shortens Zika viremia.

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          Most cited references43

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          Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus.

          Zika virus (ZIKV) is an emerging mosquito-borne flavivirus of significant public health concern. ZIKV shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (DENV), resulting in immunological cross-reactivity. Improving our current understanding of the extent and characteristics of this immunological cross-reactivity is important, as ZIKV is presently circulating in areas that are highly endemic for dengue. To assess the magnitude and functional quality of cross-reactive immune responses between these closely related viruses, we tested acute and convalescent sera from nine Thai patients with PCR-confirmed DENV infection against ZIKV. All of the sera tested were cross-reactive with ZIKV, both in binding and in neutralization. To deconstruct the observed serum cross-reactivity in depth, we also characterized a panel of DENV-specific plasmablast-derived monoclonal antibodies (mAbs) for activity against ZIKV. Nearly half of the 47 DENV-reactive mAbs studied bound to both whole ZIKV virion and ZIKV lysate, of which a subset also neutralized ZIKV. In addition, both sera and mAbs from the dengue-infected patients enhanced ZIKV infection of Fc gamma receptor (FcγR)-bearing cells in vitro. Taken together, these findings suggest that preexisting immunity to DENV may impact protective immune responses against ZIKV. In addition, the extensive cross-reactivity may have implications for ZIKV virulence and disease severity in DENV-experienced populations.
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            Multiprocess 3D printing for increasing component functionality.

            Layer-by-layer deposition of materials to manufacture parts-better known as three-dimensional (3D) printing or additive manufacturing-has been flourishing as a fabrication process in the past several years and now can create complex geometries for use as models, assembly fixtures, and production molds. Increasing interest has focused on the use of this technology for direct manufacturing of production parts; however, it remains generally limited to single-material fabrication, which can limit the end-use functionality of the fabricated structures. The next generation of 3D printing will entail not only the integration of dissimilar materials but the embedding of active components in order to deliver functionality that was not possible previously. Examples could include arbitrarily shaped electronics with integrated microfluidic thermal management and intelligent prostheses custom-fit to the anatomy of a specific patient. We review the state of the art in multiprocess (or hybrid) 3D printing, in which complementary processes, both novel and traditional, are combined to advance the future of manufacturing.
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              Follicular helper T cells: lineage and location.

              Follicular helper T (Tfh) cells are the class of effector T helper cells that regulates the step-wise development of antigen-specific B cell immunity in vivo. Deployment of CXCR5+ Tfh cells to B cell zones of lymphoid tissues and stable cognate interactions with B cells are central to the delivery of antigen-specific Tfh cell function. Here, we review recent advances that have helped to unravel distinctive elements of developmental programming for Tfh cells and unique effector Tfh cell functions focused on antigen-primed B cells. Understanding the regulatory functions of Tfh cells in the germinal center and the subsequent regulation of memory B cell responses to antigen recall represent the frontiers of this research area with the potential to alter fundamentally the design of future vaccines.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group
                2041-1723
                23 June 2017
                2017
                : 8
                : 15674
                Affiliations
                [1 ]Unit of Comparative Medicine, Caribbean Primate Research Center, University of Puerto Rico-Medical Sciences Campus , San Juan, Puerto Rico 00952, USA
                [2 ]Department of Microbiology and Medical Zoology, University of Puerto Rico-Medical Sciences Campus , San Juan, Puerto Rico 00936, USA
                [3 ]Department of Microbiology and Immunology, University of North Carolina-Chapel Hill , North Carolina 27599, USA
                [4 ]Texas Biomedical Research Institute , San Antonio, Texas 78227, USA
                [5 ]Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine , Saint Louis, Missouri 63104, USA
                [6 ]Department of Internal Medicine, University of Puerto Rico-Medical Sciences Campus , San Juan, Puerto Rico 00936, USA
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                ncomms15674
                10.1038/ncomms15674
                5490051
                28643775
                3fbc20c9-b256-4f81-8fe9-8aaefded80ca
                Copyright © 2017, The Author(s)

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 08 December 2016
                : 19 April 2017
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