Zika Virus Infection of Human Mesenchymal Stem Cells Promotes Differential Expression of Proteins Linked to Several Neurological Diseases
The recent microcephaly outbreak in Brazil has been associated with Zika virus (ZIKV) infection. The current understanding of damage caused by ZIKV infection is still unclear, since it has been implicated in other neurodegenerative and developmental complications. Here, the differential proteome ana...
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| Veröffentlicht in: | Molecular neurobiology 2019-07, Vol.56 (7), p.4708-4717 |
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| creator | Beys-da-Silva, Walter O. Rosa, Rafael L. Santi, Lucélia Berger, Markus Park, Sung Kyu Campos, Alexandre R. Terraciano, Paula Varela, Ana Paula M. Teixeira, Thais F. Roehe, Paulo M. Quincozes-Santos, André Yates, John R. Souza, Diogo O. Cirne-Lima, Elizabeth O. Guimarães, Jorge A. |
| description | The recent microcephaly outbreak in Brazil has been associated with Zika virus (ZIKV) infection. The current understanding of damage caused by ZIKV infection is still unclear, since it has been implicated in other neurodegenerative and developmental complications. Here, the differential proteome analysis of human mesenchymal stem cells (hMSC) infected with a Brazilian strain of ZIKV was identified by shotgun proteomics (MudPIT). Our results indicate that ZIKV induces a potential reprogramming of the metabolic machinery in nucleotide metabolism, changes in the energy production via glycolysis and other metabolic pathways, and potentially inhibits autophagy, neurogenesis, and immune response by downregulation of signaling pathways. In addition, proteins previously described in several brain pathologies, such as Alzheimer’s disease, autism spectrum disorder, amyotrophic lateral sclerosis, and Parkinson’s disease, were found with altered expression due to ZIKV infection in hMSC. This potential link between ZIKV and several neuropathologies beyond microcephaly is being described here for the first time and can be used to guide specific follow-up studies concerning these specific diseases and ZIKV infection. |
| doi_str_mv | 10.1007/s12035-018-1417-x |
| format | Article |
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The current understanding of damage caused by ZIKV infection is still unclear, since it has been implicated in other neurodegenerative and developmental complications. Here, the differential proteome analysis of human mesenchymal stem cells (hMSC) infected with a Brazilian strain of ZIKV was identified by shotgun proteomics (MudPIT). Our results indicate that ZIKV induces a potential reprogramming of the metabolic machinery in nucleotide metabolism, changes in the energy production via glycolysis and other metabolic pathways, and potentially inhibits autophagy, neurogenesis, and immune response by downregulation of signaling pathways. In addition, proteins previously described in several brain pathologies, such as Alzheimer’s disease, autism spectrum disorder, amyotrophic lateral sclerosis, and Parkinson’s disease, were found with altered expression due to ZIKV infection in hMSC. This potential link between ZIKV and several neuropathologies beyond microcephaly is being described here for the first time and can be used to guide specific follow-up studies concerning these specific diseases and ZIKV infection.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-018-1417-x</identifier><identifier>PMID: 30377986</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adult ; Alzheimer's disease ; Amyotrophic lateral sclerosis ; Autism ; Autophagy ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Complications ; Energy metabolism ; Female ; Glycolysis ; Humans ; Immune response ; Infections ; Mesenchymal stem cells ; Mesenchymal Stem Cells - metabolism ; Mesenchyme ; Metabolic pathways ; Metabolism ; Microcephaly ; Microencephaly ; Movement disorders ; Nervous System Diseases - pathology ; Nervous System Diseases - virology ; Neurobiology ; Neurodegenerative diseases ; Neurogenesis ; Neurological diseases ; Neurology ; Neurosciences ; Outbreaks ; Parkinson's disease ; Phagocytosis ; Proteins ; Proteome - metabolism ; Proteomes ; Proteomics ; Stem cells ; Vector-borne diseases ; Viruses ; Zika virus ; Zika Virus - physiology ; Zika Virus Infection - metabolism ; Zika Virus Infection - pathology</subject><ispartof>Molecular neurobiology, 2019-07, Vol.56 (7), p.4708-4717</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2018</rights><rights>Molecular Neurobiology is a copyright of Springer, (2018). All Rights Reserved.</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2018.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c498t-3d10da76a7e47db122684de0ee002a26e6f0d0dcee1c9b04ff8365c8fe6c619c3</citedby><cites>FETCH-LOGICAL-c498t-3d10da76a7e47db122684de0ee002a26e6f0d0dcee1c9b04ff8365c8fe6c619c3</cites><orcidid>0000-0001-8329-7839</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-018-1417-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-018-1417-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27922,27923,41486,42555,51317</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30377986$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Beys-da-Silva, Walter O.</creatorcontrib><creatorcontrib>Rosa, Rafael L.</creatorcontrib><creatorcontrib>Santi, Lucélia</creatorcontrib><creatorcontrib>Berger, Markus</creatorcontrib><creatorcontrib>Park, Sung Kyu</creatorcontrib><creatorcontrib>Campos, Alexandre R.</creatorcontrib><creatorcontrib>Terraciano, Paula</creatorcontrib><creatorcontrib>Varela, Ana Paula M.</creatorcontrib><creatorcontrib>Teixeira, Thais F.</creatorcontrib><creatorcontrib>Roehe, Paulo M.</creatorcontrib><creatorcontrib>Quincozes-Santos, André</creatorcontrib><creatorcontrib>Yates, John R.</creatorcontrib><creatorcontrib>Souza, Diogo O.</creatorcontrib><creatorcontrib>Cirne-Lima, Elizabeth O.</creatorcontrib><creatorcontrib>Guimarães, Jorge A.</creatorcontrib><title>Zika Virus Infection of Human Mesenchymal Stem Cells Promotes Differential Expression of Proteins Linked to Several Neurological Diseases</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><description>The recent microcephaly outbreak in Brazil has been associated with Zika virus (ZIKV) infection. The current understanding of damage caused by ZIKV infection is still unclear, since it has been implicated in other neurodegenerative and developmental complications. Here, the differential proteome analysis of human mesenchymal stem cells (hMSC) infected with a Brazilian strain of ZIKV was identified by shotgun proteomics (MudPIT). Our results indicate that ZIKV induces a potential reprogramming of the metabolic machinery in nucleotide metabolism, changes in the energy production via glycolysis and other metabolic pathways, and potentially inhibits autophagy, neurogenesis, and immune response by downregulation of signaling pathways. In addition, proteins previously described in several brain pathologies, such as Alzheimer’s disease, autism spectrum disorder, amyotrophic lateral sclerosis, and Parkinson’s disease, were found with altered expression due to ZIKV infection in hMSC. This potential link between ZIKV and several neuropathologies beyond microcephaly is being described here for the first time and can be used to guide specific follow-up studies concerning these specific diseases and ZIKV infection.</description><subject>Adult</subject><subject>Alzheimer's disease</subject><subject>Amyotrophic lateral sclerosis</subject><subject>Autism</subject><subject>Autophagy</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Complications</subject><subject>Energy metabolism</subject><subject>Female</subject><subject>Glycolysis</subject><subject>Humans</subject><subject>Immune response</subject><subject>Infections</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>Mesenchyme</subject><subject>Metabolic pathways</subject><subject>Metabolism</subject><subject>Microcephaly</subject><subject>Microencephaly</subject><subject>Movement disorders</subject><subject>Nervous System Diseases - pathology</subject><subject>Nervous System Diseases - virology</subject><subject>Neurobiology</subject><subject>Neurodegenerative diseases</subject><subject>Neurogenesis</subject><subject>Neurological diseases</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Outbreaks</subject><subject>Parkinson's disease</subject><subject>Phagocytosis</subject><subject>Proteins</subject><subject>Proteome - metabolism</subject><subject>Proteomes</subject><subject>Proteomics</subject><subject>Stem cells</subject><subject>Vector-borne diseases</subject><subject>Viruses</subject><subject>Zika virus</subject><subject>Zika Virus - physiology</subject><subject>Zika Virus Infection - metabolism</subject><subject>Zika Virus Infection - pathology</subject><issn>0893-7648</issn><issn>1559-1182</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9ks1uEzEUhS0EoqHwAGyQJTZsBmzPjO3ZIKG00ErhRyqwYGM5nuvUbcZOfWeq9BF4a1wllB8JVpZ1v3t8z_Uh5ClnLzlj6hVyweq2YlxXvOGq2t4jM962XcW5FvfJjOmurpRs9AF5hHjBmBCcqYfkoGa1Up2WM_L9W7i09GvIE9LT6MGNIUWaPD2ZBhvpe0CI7vxmsGt6NsJA57BeI_2U05BGQHoUvIcMcQwFON5uMiDuBQozQohIFyFeQk_HRM_gGnIBP8CU0zqtgiuXo4BgEfAxeeDtGuHJ_jwkX94ef56fVIuP707nbxaVazo9VnXPWW-VtAoa1S-5EFI3PTCAYs8KCdKznvUOgLtuyRrvdS1bpz1IJ3nn6kPyeqe7mZYDFDCOZSazyWGw-cYkG8yflRjOzSpdG9l0XKimCLzYC-R0NQGOZgjoyl5shDShEYWSkolOFPT5X-hFmnIs9oyQXStkI-r6v1TRYh1nWheK7yiXE2IGfzcyZ-Y2DmYXB1PiYG7jYLal59nvXu86fv5_AcQOwFKKK8i_nv636g-ZisMx</recordid><startdate>20190701</startdate><enddate>20190701</enddate><creator>Beys-da-Silva, Walter O.</creator><creator>Rosa, Rafael L.</creator><creator>Santi, Lucélia</creator><creator>Berger, Markus</creator><creator>Park, Sung Kyu</creator><creator>Campos, Alexandre R.</creator><creator>Terraciano, Paula</creator><creator>Varela, Ana Paula M.</creator><creator>Teixeira, Thais F.</creator><creator>Roehe, Paulo M.</creator><creator>Quincozes-Santos, André</creator><creator>Yates, John R.</creator><creator>Souza, Diogo O.</creator><creator>Cirne-Lima, Elizabeth O.</creator><creator>Guimarães, Jorge A.</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QR</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8329-7839</orcidid></search><sort><creationdate>20190701</creationdate><title>Zika Virus Infection of Human Mesenchymal Stem Cells Promotes Differential Expression of Proteins Linked to Several Neurological Diseases</title><author>Beys-da-Silva, Walter O. ; Rosa, Rafael L. ; Santi, Lucélia ; Berger, Markus ; Park, Sung Kyu ; Campos, Alexandre R. ; Terraciano, Paula ; Varela, Ana Paula M. ; Teixeira, Thais F. ; Roehe, Paulo M. ; Quincozes-Santos, André ; Yates, John R. ; Souza, Diogo O. ; Cirne-Lima, Elizabeth O. ; Guimarães, Jorge A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c498t-3d10da76a7e47db122684de0ee002a26e6f0d0dcee1c9b04ff8365c8fe6c619c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Alzheimer's disease</topic><topic>Amyotrophic lateral sclerosis</topic><topic>Autism</topic><topic>Autophagy</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>Complications</topic><topic>Energy metabolism</topic><topic>Female</topic><topic>Glycolysis</topic><topic>Humans</topic><topic>Immune response</topic><topic>Infections</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stem Cells - metabolism</topic><topic>Mesenchyme</topic><topic>Metabolic pathways</topic><topic>Metabolism</topic><topic>Microcephaly</topic><topic>Microencephaly</topic><topic>Movement disorders</topic><topic>Nervous System Diseases - pathology</topic><topic>Nervous System Diseases - virology</topic><topic>Neurobiology</topic><topic>Neurodegenerative diseases</topic><topic>Neurogenesis</topic><topic>Neurological diseases</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Outbreaks</topic><topic>Parkinson's disease</topic><topic>Phagocytosis</topic><topic>Proteins</topic><topic>Proteome - metabolism</topic><topic>Proteomes</topic><topic>Proteomics</topic><topic>Stem cells</topic><topic>Vector-borne diseases</topic><topic>Viruses</topic><topic>Zika virus</topic><topic>Zika Virus - physiology</topic><topic>Zika Virus Infection - metabolism</topic><topic>Zika Virus Infection - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Beys-da-Silva, Walter O.</creatorcontrib><creatorcontrib>Rosa, Rafael L.</creatorcontrib><creatorcontrib>Santi, Lucélia</creatorcontrib><creatorcontrib>Berger, Markus</creatorcontrib><creatorcontrib>Park, Sung Kyu</creatorcontrib><creatorcontrib>Campos, Alexandre R.</creatorcontrib><creatorcontrib>Terraciano, Paula</creatorcontrib><creatorcontrib>Varela, Ana Paula M.</creatorcontrib><creatorcontrib>Teixeira, Thais F.</creatorcontrib><creatorcontrib>Roehe, Paulo M.</creatorcontrib><creatorcontrib>Quincozes-Santos, André</creatorcontrib><creatorcontrib>Yates, John R.</creatorcontrib><creatorcontrib>Souza, Diogo O.</creatorcontrib><creatorcontrib>Cirne-Lima, Elizabeth O.</creatorcontrib><creatorcontrib>Guimarães, Jorge A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - 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| ispartof | Molecular neurobiology, 2019-07, Vol.56 (7), p.4708-4717 |
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| language | eng |
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| subjects | Adult Alzheimer's disease Amyotrophic lateral sclerosis Autism Autophagy Biomedical and Life Sciences Biomedicine Cell Biology Complications Energy metabolism Female Glycolysis Humans Immune response Infections Mesenchymal stem cells Mesenchymal Stem Cells - metabolism Mesenchyme Metabolic pathways Metabolism Microcephaly Microencephaly Movement disorders Nervous System Diseases - pathology Nervous System Diseases - virology Neurobiology Neurodegenerative diseases Neurogenesis Neurological diseases Neurology Neurosciences Outbreaks Parkinson's disease Phagocytosis Proteins Proteome - metabolism Proteomes Proteomics Stem cells Vector-borne diseases Viruses Zika virus Zika Virus - physiology Zika Virus Infection - metabolism Zika Virus Infection - pathology |
| title | Zika Virus Infection of Human Mesenchymal Stem Cells Promotes Differential Expression of Proteins Linked to Several Neurological Diseases |
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