Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain.
During HIV/SIV infection, there is widespread programmed cell death in infected and, perhaps more importantly, uninfected cells. Much of this apoptosis is mediated by Fas-Fas ligand (FasL) interactions. Previously we demonstrated in macaques that induction of FasL expression and apoptotic cell death...
| मुख्य लेखकों: | , , , , , , , , |
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| स्वरूप: | Journal article |
| भाषा: | English |
| प्रकाशित: |
1999
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| _version_ | 1826260512423280640 |
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| author | Xu, X Laffert, B Screaton, G Kraft, M Wolf, D Kolanus, W Mongkolsapay, J Mcmichael, A Baur, A |
| author_facet | Xu, X Laffert, B Screaton, G Kraft, M Wolf, D Kolanus, W Mongkolsapay, J Mcmichael, A Baur, A |
| author_sort | Xu, X |
| collection | OXFORD |
| description | During HIV/SIV infection, there is widespread programmed cell death in infected and, perhaps more importantly, uninfected cells. Much of this apoptosis is mediated by Fas-Fas ligand (FasL) interactions. Previously we demonstrated in macaques that induction of FasL expression and apoptotic cell death of both CD4(+) and CD8(+) T cells by SIV is dependent on a functional nef gene. However, the molecular mechanism whereby HIV-1 induces the expression of FasL remained poorly understood. Here we report a direct association of HIV-1 Nef with the zeta chain of the T cell receptor (TCR) complex and the requirement of both proteins for HIV-mediated upregulation of FasL. Expression of FasL through Nef depended upon the integrity of the immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR zeta chain. Conformation for the importance of zeta for Nef-mediated signaling in T cells came from an independent finding. A single ITAM motif of zeta but not CD3epsilon was both required and sufficient to promote activation and binding of the Nef-associated kinase (NAK/p62). Our data imply that Nef can form a signaling complex with the TCR, which bypasses the requirement of antigen to initiate T cell activation and subsequently upregulation of FasL expression. Thus, our study may provide critical insights into the molecular mechanism whereby the HIV-1 accessory protein Nef contributes to the pathogenesis of HIV. |
| first_indexed | 2024-03-06T19:06:49Z |
| format | Journal article |
| id | oxford-uuid:156cb12b-6d2b-40b3-a776-d2294d0092ff |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:06:49Z |
| publishDate | 1999 |
| record_format | dspace |
| spelling | oxford-uuid:156cb12b-6d2b-40b3-a776-d2294d0092ff2022-03-26T10:25:22ZInduction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:156cb12b-6d2b-40b3-a776-d2294d0092ffEnglishSymplectic Elements at Oxford1999Xu, XLaffert, BScreaton, GKraft, MWolf, DKolanus, WMongkolsapay, JMcmichael, ABaur, ADuring HIV/SIV infection, there is widespread programmed cell death in infected and, perhaps more importantly, uninfected cells. Much of this apoptosis is mediated by Fas-Fas ligand (FasL) interactions. Previously we demonstrated in macaques that induction of FasL expression and apoptotic cell death of both CD4(+) and CD8(+) T cells by SIV is dependent on a functional nef gene. However, the molecular mechanism whereby HIV-1 induces the expression of FasL remained poorly understood. Here we report a direct association of HIV-1 Nef with the zeta chain of the T cell receptor (TCR) complex and the requirement of both proteins for HIV-mediated upregulation of FasL. Expression of FasL through Nef depended upon the integrity of the immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR zeta chain. Conformation for the importance of zeta for Nef-mediated signaling in T cells came from an independent finding. A single ITAM motif of zeta but not CD3epsilon was both required and sufficient to promote activation and binding of the Nef-associated kinase (NAK/p62). Our data imply that Nef can form a signaling complex with the TCR, which bypasses the requirement of antigen to initiate T cell activation and subsequently upregulation of FasL expression. Thus, our study may provide critical insights into the molecular mechanism whereby the HIV-1 accessory protein Nef contributes to the pathogenesis of HIV. |
| spellingShingle | Xu, X Laffert, B Screaton, G Kraft, M Wolf, D Kolanus, W Mongkolsapay, J Mcmichael, A Baur, A Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain. |
| title | Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain. |
| title_full | Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain. |
| title_fullStr | Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain. |
| title_full_unstemmed | Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain. |
| title_short | Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain. |
| title_sort | induction of fas ligand expression by hiv involves the interaction of nef with the t cell receptor zeta chain |
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