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Enhanced Human Immunodeficiency Virus Type 1 Expression and Neuropathogenesis in Knockout Mice Lacking Type I Interferon Responses

The roles of Type I interferon (IFN) in human immunodeficiency virus Type 1 (HIV-1) neuropathogenesis are poorly understood; both protective and deleterious effects of IFN signaling have been described. We used genetically modified mice deficient in the Type I IFN receptor (IFNRKO) to analyze the pr...

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Autores principales: He, Hongxia, Sharer, Leroy R., Chao, Wei, Gu, Chao-Jiang, Borjabad, Alejandra, Hadas, Eran, Kelschenbach, Jennifer, Ichiyama, Koji, Do, Meilan, Potash, Mary Jane, Volsky, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association of Neuropathologists 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871403/
https://www.ncbi.nlm.nih.gov/pubmed/24335529
http://dx.doi.org/10.1097/NEN.0000000000000026
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author He, Hongxia
Sharer, Leroy R.
Chao, Wei
Gu, Chao-Jiang
Borjabad, Alejandra
Hadas, Eran
Kelschenbach, Jennifer
Ichiyama, Koji
Do, Meilan
Potash, Mary Jane
Volsky, David J.
author_facet He, Hongxia
Sharer, Leroy R.
Chao, Wei
Gu, Chao-Jiang
Borjabad, Alejandra
Hadas, Eran
Kelschenbach, Jennifer
Ichiyama, Koji
Do, Meilan
Potash, Mary Jane
Volsky, David J.
author_sort He, Hongxia
collection PubMed
description The roles of Type I interferon (IFN) in human immunodeficiency virus Type 1 (HIV-1) neuropathogenesis are poorly understood; both protective and deleterious effects of IFN signaling have been described. We used genetically modified mice deficient in the Type I IFN receptor (IFNRKO) to analyze the progress of HIV-1 brain infection and neuropathogenesis in the absence of IFN signaling. IFNRKO and wild-type (WT) mice on the 129xSv/Ev or C57BL/6 strain backgrounds were infected systemically with EcoHIV, a chimeric HIV-1 that productively infects mice. IFNRKO mice showed higher HIV-1 expression in spleen and peritoneal macrophages and greater virus infiltration into the brain compared to WT mice. Neuropathogenesis was studied by histopathological, immunohistochemical, immunofluorescence, and polymerase chain reaction analyses of brain tissues after the virus was inoculated into the brain by stereotaxic intracerebral injection. Both IFNRKO and WT mice showed readily detectable HIV-1 and brain lesions, including microglial activation, astrocytosis, and increased expression of genes coding for inflammatory cytokines and chemokines typical of human HIV-1 brain disease. Parameters of HIV-1 neuropathogenesis, including HIV-1 expression in microglia/macrophages, were significantly greater in IFNRKO than in WT mice. Our results show unequivocally that Type I IFN signaling and responses limit HIV-1 infection and pathogenesis in the brains of mice.
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spelling pubmed-38714032013-12-26 Enhanced Human Immunodeficiency Virus Type 1 Expression and Neuropathogenesis in Knockout Mice Lacking Type I Interferon Responses He, Hongxia Sharer, Leroy R. Chao, Wei Gu, Chao-Jiang Borjabad, Alejandra Hadas, Eran Kelschenbach, Jennifer Ichiyama, Koji Do, Meilan Potash, Mary Jane Volsky, David J. J Neuropathol Exp Neurol Original Articles The roles of Type I interferon (IFN) in human immunodeficiency virus Type 1 (HIV-1) neuropathogenesis are poorly understood; both protective and deleterious effects of IFN signaling have been described. We used genetically modified mice deficient in the Type I IFN receptor (IFNRKO) to analyze the progress of HIV-1 brain infection and neuropathogenesis in the absence of IFN signaling. IFNRKO and wild-type (WT) mice on the 129xSv/Ev or C57BL/6 strain backgrounds were infected systemically with EcoHIV, a chimeric HIV-1 that productively infects mice. IFNRKO mice showed higher HIV-1 expression in spleen and peritoneal macrophages and greater virus infiltration into the brain compared to WT mice. Neuropathogenesis was studied by histopathological, immunohistochemical, immunofluorescence, and polymerase chain reaction analyses of brain tissues after the virus was inoculated into the brain by stereotaxic intracerebral injection. Both IFNRKO and WT mice showed readily detectable HIV-1 and brain lesions, including microglial activation, astrocytosis, and increased expression of genes coding for inflammatory cytokines and chemokines typical of human HIV-1 brain disease. Parameters of HIV-1 neuropathogenesis, including HIV-1 expression in microglia/macrophages, were significantly greater in IFNRKO than in WT mice. Our results show unequivocally that Type I IFN signaling and responses limit HIV-1 infection and pathogenesis in the brains of mice. American Association of Neuropathologists 2014-01 2013-12-19 /pmc/articles/PMC3871403/ /pubmed/24335529 http://dx.doi.org/10.1097/NEN.0000000000000026 Text en Copyright © 2013 by the American Association of Neuropathologists, Inc. http://creativecommons.org/licenses/by-nc-nd/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
spellingShingle Original Articles
He, Hongxia
Sharer, Leroy R.
Chao, Wei
Gu, Chao-Jiang
Borjabad, Alejandra
Hadas, Eran
Kelschenbach, Jennifer
Ichiyama, Koji
Do, Meilan
Potash, Mary Jane
Volsky, David J.
Enhanced Human Immunodeficiency Virus Type 1 Expression and Neuropathogenesis in Knockout Mice Lacking Type I Interferon Responses
title Enhanced Human Immunodeficiency Virus Type 1 Expression and Neuropathogenesis in Knockout Mice Lacking Type I Interferon Responses
title_full Enhanced Human Immunodeficiency Virus Type 1 Expression and Neuropathogenesis in Knockout Mice Lacking Type I Interferon Responses
title_fullStr Enhanced Human Immunodeficiency Virus Type 1 Expression and Neuropathogenesis in Knockout Mice Lacking Type I Interferon Responses
title_full_unstemmed Enhanced Human Immunodeficiency Virus Type 1 Expression and Neuropathogenesis in Knockout Mice Lacking Type I Interferon Responses
title_short Enhanced Human Immunodeficiency Virus Type 1 Expression and Neuropathogenesis in Knockout Mice Lacking Type I Interferon Responses
title_sort enhanced human immunodeficiency virus type 1 expression and neuropathogenesis in knockout mice lacking type i interferon responses
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871403/
https://www.ncbi.nlm.nih.gov/pubmed/24335529
http://dx.doi.org/10.1097/NEN.0000000000000026
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