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The cytoskeletal adaptor obscurin-like 1 interacts with the human papillomavirus 16 (HPV16) capsid protein L2 and is required for HPV16 endocytosis

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Veröffentlicht in: Journal of virology 90(2016), 23, Seite 10629-10641
Personen und Körperschaften: Wüstenhagen, Elena (VerfasserIn), Schneider, Marc (VerfasserIn)
Titel: The cytoskeletal adaptor obscurin-like 1 interacts with the human papillomavirus 16 (HPV16) capsid protein L2 and is required for HPV16 endocytosis/ Elena Wüstenhagen, Laura Hampe, Fatima Boukhallouk, Marc A. Schneider, Gilles A. Spoden, Inka Negwer, Kaloian Koynov, W. Martin Kast, Luise Florin
Format: E-Book-Kapitel
Sprache: Englisch
veröffentlicht:
21 September 2016
Gesamtaufnahme: : Journal of virology, 90(2016), 23, Seite 10629-10641
, volume:90
Quelle: Verbunddaten SWB
Lizenzfreie Online-Ressourcen
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520 |a The human papillomavirus (HPV) capsid protein L2 is essential for viral entry. To gain a deeper understanding of the role of L2, we searched for novel cellular L2-interacting proteins. A yeast two-hybrid analysis uncovered the actin-depolymerizing factor gelsolin, the membrane glycoprotein dysadherin, the centrosomal protein 68 (Cep68), and the cytoskeletal adaptor protein obscurin-like 1 protein (OBSL1) as putative L2 binding molecules. Pseudovirus (PsV) infection assays identified OBSL1 as a host factor required for gene transduction by three oncogenic human papillomavirus types, HPV16, HPV18, and HPV31. In addition, we detected OBSL1 expression in cervical tissue sections and noted the involvement of OBSL1 during gene transduction of primary keratinocytes by HPV16 PsV. Complex formation of HPV16 L2 with OBSL1 was demonstrated in coimmunofluorescence and coimmunoprecipitation studies after overexpression of L2 or after PsV exposure. We observed a strong colocalization of OBSL1 with HPV16 PsV and tetraspanin CD151 at the plasma membrane, suggesting a role for OBSL1 in viral endocytosis. Indeed, viral entry assays exhibited a reduction of viral endocytosis in OBSL1-depleted cells. Our results suggest OBSL1 as a novel L2-interacting protein and endocytosis factor in HPV infection., IMPORTANCE Human papillomaviruses infect mucosal and cutaneous epithelia, and the high-risk HPV types account for 5% of cancer cases worldwide. As recently discovered, HPV entry occurs by a clathrin-, caveolin-, and dynamin-independent endocytosis via tetraspanin-enriched microdomains. At present, the cellular proteins involved in the underlying mechanism of this type of endocytosis are under investigation. In this study, the cytoskeletal adaptor OBSL1 was discovered as a previously unrecognized interaction partner of the minor capsid protein L2 and was identified as a proviral host factor required for HPV16 endocytosis into target cells. The findings of this study advance the understanding of a so far less well-characterized endocytic pathway that is used by oncogenic HPV subtypes. 
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contents The human papillomavirus (HPV) capsid protein L2 is essential for viral entry. To gain a deeper understanding of the role of L2, we searched for novel cellular L2-interacting proteins. A yeast two-hybrid analysis uncovered the actin-depolymerizing factor gelsolin, the membrane glycoprotein dysadherin, the centrosomal protein 68 (Cep68), and the cytoskeletal adaptor protein obscurin-like 1 protein (OBSL1) as putative L2 binding molecules. Pseudovirus (PsV) infection assays identified OBSL1 as a host factor required for gene transduction by three oncogenic human papillomavirus types, HPV16, HPV18, and HPV31. In addition, we detected OBSL1 expression in cervical tissue sections and noted the involvement of OBSL1 during gene transduction of primary keratinocytes by HPV16 PsV. Complex formation of HPV16 L2 with OBSL1 was demonstrated in coimmunofluorescence and coimmunoprecipitation studies after overexpression of L2 or after PsV exposure. We observed a strong colocalization of OBSL1 with HPV16 PsV and tetraspanin CD151 at the plasma membrane, suggesting a role for OBSL1 in viral endocytosis. Indeed, viral entry assays exhibited a reduction of viral endocytosis in OBSL1-depleted cells. Our results suggest OBSL1 as a novel L2-interacting protein and endocytosis factor in HPV infection., IMPORTANCE Human papillomaviruses infect mucosal and cutaneous epithelia, and the high-risk HPV types account for 5% of cancer cases worldwide. As recently discovered, HPV entry occurs by a clathrin-, caveolin-, and dynamin-independent endocytosis via tetraspanin-enriched microdomains. At present, the cellular proteins involved in the underlying mechanism of this type of endocytosis are under investigation. In this study, the cytoskeletal adaptor OBSL1 was discovered as a previously unrecognized interaction partner of the minor capsid protein L2 and was identified as a proviral host factor required for HPV16 endocytosis into target cells. The findings of this study advance the understanding of a so far less well-characterized endocytic pathway that is used by oncogenic HPV subtypes.
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spelling Wüstenhagen, Elena VerfasserIn (DE-588)1142544575 (DE-627)1002243122 (DE-576)494841060 aut, The cytoskeletal adaptor obscurin-like 1 interacts with the human papillomavirus 16 (HPV16) capsid protein L2 and is required for HPV16 endocytosis Elena Wüstenhagen, Laura Hampe, Fatima Boukhallouk, Marc A. Schneider, Gilles A. Spoden, Inka Negwer, Kaloian Koynov, W. Martin Kast, Luise Florin, 21 September 2016, 13, Text txt rdacontent, Computermedien c rdamedia, Online-Ressource cr rdacarrier, Gesehen am 27.10.2017, The human papillomavirus (HPV) capsid protein L2 is essential for viral entry. To gain a deeper understanding of the role of L2, we searched for novel cellular L2-interacting proteins. A yeast two-hybrid analysis uncovered the actin-depolymerizing factor gelsolin, the membrane glycoprotein dysadherin, the centrosomal protein 68 (Cep68), and the cytoskeletal adaptor protein obscurin-like 1 protein (OBSL1) as putative L2 binding molecules. Pseudovirus (PsV) infection assays identified OBSL1 as a host factor required for gene transduction by three oncogenic human papillomavirus types, HPV16, HPV18, and HPV31. In addition, we detected OBSL1 expression in cervical tissue sections and noted the involvement of OBSL1 during gene transduction of primary keratinocytes by HPV16 PsV. Complex formation of HPV16 L2 with OBSL1 was demonstrated in coimmunofluorescence and coimmunoprecipitation studies after overexpression of L2 or after PsV exposure. We observed a strong colocalization of OBSL1 with HPV16 PsV and tetraspanin CD151 at the plasma membrane, suggesting a role for OBSL1 in viral endocytosis. Indeed, viral entry assays exhibited a reduction of viral endocytosis in OBSL1-depleted cells. Our results suggest OBSL1 as a novel L2-interacting protein and endocytosis factor in HPV infection., IMPORTANCE Human papillomaviruses infect mucosal and cutaneous epithelia, and the high-risk HPV types account for 5% of cancer cases worldwide. As recently discovered, HPV entry occurs by a clathrin-, caveolin-, and dynamin-independent endocytosis via tetraspanin-enriched microdomains. At present, the cellular proteins involved in the underlying mechanism of this type of endocytosis are under investigation. In this study, the cytoskeletal adaptor OBSL1 was discovered as a previously unrecognized interaction partner of the minor capsid protein L2 and was identified as a proviral host factor required for HPV16 endocytosis into target cells. The findings of this study advance the understanding of a so far less well-characterized endocytic pathway that is used by oncogenic HPV subtypes., Schneider, Marc 1981- VerfasserIn (DE-588)140634401 (DE-627)620239948 (DE-576)319208095 aut, Enthalten in Journal of virology Baltimore, Md. : Soc., 1967 90(2016), 23, Seite 10629-10641 Online-Ressource (DE-627)303614609 (DE-600)1495529-5 (DE-576)08088766X 1098-5514 nnns, volume:90 year:2016 number:23 pages:10629-10641 extent:13, http://dx.doi.org/10.1128/JVI.01222-16 Verlag Resolving-System kostenfrei Volltext, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5110159/ Verlag kostenfrei Volltext, http://dx.doi.org/10.1128/JVI.01222-16 LFER, LFER 2017-11-13T00:00:00Z
spellingShingle Wüstenhagen, Elena, Schneider, Marc, The cytoskeletal adaptor obscurin-like 1 interacts with the human papillomavirus 16 (HPV16) capsid protein L2 and is required for HPV16 endocytosis, The human papillomavirus (HPV) capsid protein L2 is essential for viral entry. To gain a deeper understanding of the role of L2, we searched for novel cellular L2-interacting proteins. A yeast two-hybrid analysis uncovered the actin-depolymerizing factor gelsolin, the membrane glycoprotein dysadherin, the centrosomal protein 68 (Cep68), and the cytoskeletal adaptor protein obscurin-like 1 protein (OBSL1) as putative L2 binding molecules. Pseudovirus (PsV) infection assays identified OBSL1 as a host factor required for gene transduction by three oncogenic human papillomavirus types, HPV16, HPV18, and HPV31. In addition, we detected OBSL1 expression in cervical tissue sections and noted the involvement of OBSL1 during gene transduction of primary keratinocytes by HPV16 PsV. Complex formation of HPV16 L2 with OBSL1 was demonstrated in coimmunofluorescence and coimmunoprecipitation studies after overexpression of L2 or after PsV exposure. We observed a strong colocalization of OBSL1 with HPV16 PsV and tetraspanin CD151 at the plasma membrane, suggesting a role for OBSL1 in viral endocytosis. Indeed, viral entry assays exhibited a reduction of viral endocytosis in OBSL1-depleted cells. Our results suggest OBSL1 as a novel L2-interacting protein and endocytosis factor in HPV infection., IMPORTANCE Human papillomaviruses infect mucosal and cutaneous epithelia, and the high-risk HPV types account for 5% of cancer cases worldwide. As recently discovered, HPV entry occurs by a clathrin-, caveolin-, and dynamin-independent endocytosis via tetraspanin-enriched microdomains. At present, the cellular proteins involved in the underlying mechanism of this type of endocytosis are under investigation. In this study, the cytoskeletal adaptor OBSL1 was discovered as a previously unrecognized interaction partner of the minor capsid protein L2 and was identified as a proviral host factor required for HPV16 endocytosis into target cells. The findings of this study advance the understanding of a so far less well-characterized endocytic pathway that is used by oncogenic HPV subtypes.
swb_id_str 494841443
title The cytoskeletal adaptor obscurin-like 1 interacts with the human papillomavirus 16 (HPV16) capsid protein L2 and is required for HPV16 endocytosis
title_auth The cytoskeletal adaptor obscurin-like 1 interacts with the human papillomavirus 16 (HPV16) capsid protein L2 and is required for HPV16 endocytosis
title_full The cytoskeletal adaptor obscurin-like 1 interacts with the human papillomavirus 16 (HPV16) capsid protein L2 and is required for HPV16 endocytosis Elena Wüstenhagen, Laura Hampe, Fatima Boukhallouk, Marc A. Schneider, Gilles A. Spoden, Inka Negwer, Kaloian Koynov, W. Martin Kast, Luise Florin
title_fullStr The cytoskeletal adaptor obscurin-like 1 interacts with the human papillomavirus 16 (HPV16) capsid protein L2 and is required for HPV16 endocytosis Elena Wüstenhagen, Laura Hampe, Fatima Boukhallouk, Marc A. Schneider, Gilles A. Spoden, Inka Negwer, Kaloian Koynov, W. Martin Kast, Luise Florin
title_full_unstemmed The cytoskeletal adaptor obscurin-like 1 interacts with the human papillomavirus 16 (HPV16) capsid protein L2 and is required for HPV16 endocytosis Elena Wüstenhagen, Laura Hampe, Fatima Boukhallouk, Marc A. Schneider, Gilles A. Spoden, Inka Negwer, Kaloian Koynov, W. Martin Kast, Luise Florin
title_in_hierarchy The cytoskeletal adaptor obscurin-like 1 interacts with the human papillomavirus 16 (HPV16) capsid protein L2 and is required for HPV16 endocytosis / Elena Wüstenhagen, Laura Hampe, Fatima Boukhallouk, Marc A. Schneider, Gilles A. Spoden, Inka Negwer, Kaloian Koynov, W. Martin Kast, Luise Florin,
title_short The cytoskeletal adaptor obscurin-like 1 interacts with the human papillomavirus 16 (HPV16) capsid protein L2 and is required for HPV16 endocytosis
title_sort cytoskeletal adaptor obscurin like 1 interacts with the human papillomavirus 16 hpv16 capsid protein l2 and is required for hpv16 endocytosis
url http://dx.doi.org/10.1128/JVI.01222-16, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5110159/