Modulation of cytokine release and gene expression by the immunosuppressive domain of gp41 of HIV-1.

The transmembrane envelope protein gp41 of the human immunodeficiency virus HIV-1 plays an important role during infection allowing fusion of the viral and cellular membrane. In addition, there is increasing evidence that gp41 may contribute to the immunodeficiency induced by HIV-1. Recombinant gp41...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Joachim Denner, Magdalena Eschricht, Michael Lauck, Marwan Semaan, Philipp Schlaermann, Hyunmi Ryu, Levent Akyüz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/74fef7838ba9457190fe30d9c783f3a9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:74fef7838ba9457190fe30d9c783f3a9
record_format	dspace
spelling	oai:doaj.org-article:74fef7838ba9457190fe30d9c783f3a92021-11-18T07:59:26ZModulation of cytokine release and gene expression by the immunosuppressive domain of gp41 of HIV-1.1932-620310.1371/journal.pone.0055199https://doaj.org/article/74fef7838ba9457190fe30d9c783f3a92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23383108/?tool=EBIhttps://doaj.org/toc/1932-6203The transmembrane envelope protein gp41 of the human immunodeficiency virus HIV-1 plays an important role during infection allowing fusion of the viral and cellular membrane. In addition, there is increasing evidence that gp41 may contribute to the immunodeficiency induced by HIV-1. Recombinant gp41 and a synthetic peptide corresponding to a highly conserved domain in gp41, the immunosuppressive (isu) domain, have been shown to inhibit mitogen-induced activation of human peripheral blood mononuclear cells (PBMCs) and to increase release of IL-6 and IL-10 from these cells. We recently reported that a single mutation in the isu domain of gp41 abrogated the immunosuppressive properties and that HIV-1 sequences containing such abrogating mutations had never been isolated from infected individuals. Here, we studied the influence of the isu peptide on the release of 66 cytokines and the expression of 27,000 genes in PBMCs. Incubation of PBMCs with isu peptide homopolymers increased the expression of 16 cytokines among them IL-6 and IL-10, and decreased that of IL-2 and CXCL9. Interestingly, the extend of cytokine modulation was donor-dependent. Among the genes up-regulated were IL-6, IL-8, IL-10 but also MMP-1, TREM-1 and IL-1beta. Most importantly, genes involved in innate immunity such as FCN1 and SEPP1 were found down-regulated. Many changes in cytokine expression demonstrated in our experiments were also found in HIV-1 infected individuals. These data indicate that the isu domain of gp41 has a broad impact on gene expression and cytokine release and therefore may be involved in HIV-1 induced immunopathogenesis.Joachim DennerMagdalena EschrichtMichael LauckMarwan SemaanPhilipp SchlaermannHyunmi RyuLevent AkyüzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e55199 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joachim Denner Magdalena Eschricht Michael Lauck Marwan Semaan Philipp Schlaermann Hyunmi Ryu Levent Akyüz Modulation of cytokine release and gene expression by the immunosuppressive domain of gp41 of HIV-1.
description	The transmembrane envelope protein gp41 of the human immunodeficiency virus HIV-1 plays an important role during infection allowing fusion of the viral and cellular membrane. In addition, there is increasing evidence that gp41 may contribute to the immunodeficiency induced by HIV-1. Recombinant gp41 and a synthetic peptide corresponding to a highly conserved domain in gp41, the immunosuppressive (isu) domain, have been shown to inhibit mitogen-induced activation of human peripheral blood mononuclear cells (PBMCs) and to increase release of IL-6 and IL-10 from these cells. We recently reported that a single mutation in the isu domain of gp41 abrogated the immunosuppressive properties and that HIV-1 sequences containing such abrogating mutations had never been isolated from infected individuals. Here, we studied the influence of the isu peptide on the release of 66 cytokines and the expression of 27,000 genes in PBMCs. Incubation of PBMCs with isu peptide homopolymers increased the expression of 16 cytokines among them IL-6 and IL-10, and decreased that of IL-2 and CXCL9. Interestingly, the extend of cytokine modulation was donor-dependent. Among the genes up-regulated were IL-6, IL-8, IL-10 but also MMP-1, TREM-1 and IL-1beta. Most importantly, genes involved in innate immunity such as FCN1 and SEPP1 were found down-regulated. Many changes in cytokine expression demonstrated in our experiments were also found in HIV-1 infected individuals. These data indicate that the isu domain of gp41 has a broad impact on gene expression and cytokine release and therefore may be involved in HIV-1 induced immunopathogenesis.
format	article
author	Joachim Denner Magdalena Eschricht Michael Lauck Marwan Semaan Philipp Schlaermann Hyunmi Ryu Levent Akyüz
author_facet	Joachim Denner Magdalena Eschricht Michael Lauck Marwan Semaan Philipp Schlaermann Hyunmi Ryu Levent Akyüz
author_sort	Joachim Denner
title	Modulation of cytokine release and gene expression by the immunosuppressive domain of gp41 of HIV-1.
title_short	Modulation of cytokine release and gene expression by the immunosuppressive domain of gp41 of HIV-1.
title_full	Modulation of cytokine release and gene expression by the immunosuppressive domain of gp41 of HIV-1.
title_fullStr	Modulation of cytokine release and gene expression by the immunosuppressive domain of gp41 of HIV-1.
title_full_unstemmed	Modulation of cytokine release and gene expression by the immunosuppressive domain of gp41 of HIV-1.
title_sort	modulation of cytokine release and gene expression by the immunosuppressive domain of gp41 of hiv-1.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/74fef7838ba9457190fe30d9c783f3a9
work_keys_str_mv	AT joachimdenner modulationofcytokinereleaseandgeneexpressionbytheimmunosuppressivedomainofgp41ofhiv1 AT magdalenaeschricht modulationofcytokinereleaseandgeneexpressionbytheimmunosuppressivedomainofgp41ofhiv1 AT michaellauck modulationofcytokinereleaseandgeneexpressionbytheimmunosuppressivedomainofgp41ofhiv1 AT marwansemaan modulationofcytokinereleaseandgeneexpressionbytheimmunosuppressivedomainofgp41ofhiv1 AT philippschlaermann modulationofcytokinereleaseandgeneexpressionbytheimmunosuppressivedomainofgp41ofhiv1 AT hyunmiryu modulationofcytokinereleaseandgeneexpressionbytheimmunosuppressivedomainofgp41ofhiv1 AT leventakyuz modulationofcytokinereleaseandgeneexpressionbytheimmunosuppressivedomainofgp41ofhiv1
_version_	1718422673886806016

Modulation of cytokine release and gene expression by the immunosuppressive domain of gp41 of HIV-1.

Ejemplares similares