Zika virus impairs the development of blood vessels in a mouse model of congenital infection.

Autor: Garcez PP; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. ppgarcez@gmail.com.; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. ppgarcez@gmail.com., Stolp HB; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. hstolp@rvc.ac.uk.; Centre for the Developing Brain, Department of Perinatal Imaging & Health, King's College London, London, UK. hstolp@rvc.ac.uk., Sravanam S; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Christoff RR; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Ferreira JCCG; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Dias AA; Microbiology Institute Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Pezzuto P; Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Higa LM; Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Barbeito-Andrés J; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Ferreira RO; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Andrade CBV; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Siqueira M; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Santos TMP; Nuclear Instrumentation Laboratory, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Drumond J; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Hoerder-Suabedissen A; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., de Lima CVF; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Tovar-Moll F; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Lopes RT; Nuclear Instrumentation Laboratory, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Fragel-Madeira L; Department of Neurobiology, Institute of Biology, Fluminense Federal University, Niterói, Brazil., Lent R; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Ortiga-Carvalho TM; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Stipursky J; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Bellio M; Microbiology Institute Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Tanuri A; Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Molnár Z; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. zoltan.molnar@dpag.ox.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2018 Aug 24; Vol. 8 (1), pp. 12774. Date of Electronic Publication: 2018 Aug 24.
DOI: 10.1038/s41598-018-31149-3
Abstrakt: Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly.
Databáze: MEDLINE
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