0000000000123204
AUTHOR
Gilles A. Spoden
showing 13 related works from this author
Inhibition by cellular vacuolar ATPase impairs human papillomavirus uncoating and infection.
2014
ABSTRACT Several viruses, including human papillomaviruses, depend on endosomal acidification for successful infection. Hence, the multisubunit enzyme vacuolar ATPase (V-ATPase), which is mainly responsible for endosome acidification in the cell, represents an attractive target for antiviral strategies. In the present study, we show that V-ATPase is required for human papillomavirus (HPV) infection and that uncoating/disassembly but not endocytosis is affected by V-ATPase inhibition. The infection inhibitory potencies of saliphenylhalamide, a proven V-ATPase inhibitor, and its derivatives, as well as those of other V-ATPase inhibitors, were analyzed on different HPV types in relevant cell l…
The Transcription Factors TBX2 and TBX3 Interact with Human Papillomavirus 16 (HPV16) L2 and Repress the Long Control Region of HPVs
2013
ABSTRACT The minor capsid protein L2 of human papillomaviruses (HPVs) has multiple functions during the viral life cycle. Although L2 is required for effective invasion and morphogenesis, only a few cellular interaction partners are known so far. Using yeast two-hybrid screening, we identified the transcription factor TBX2 as a novel interaction partner of HPV type 16 (HPV16) L2. Coimmunoprecipitations and immunofluorescence analyses confirmed the L2-TBX2 interaction and revealed that L2 also interacts with TBX3, another member of the T-box family. Transcription of the early genes during HPV infection is under the control of an upstream enhancer and early promoter region, the long control r…
An L2 SUMO interacting motif is important for PML localization and infection of human papillomavirus type 16
2014
Summary Human papillomaviruses (HPV) induce warts and cancers on skin and mucosa. The HPV16 capsid is composed of the proteins L1 and L2. After cell entry and virus disassembly, the L2 protein accompanies the viral DNA to promyelocytic leukaemia nuclear bodies (PML-NBs) within the host nuclei enabling viral transcription and replication. Multiple components of PML-NBs are regulated by small ubiquitin-like modifiers (SUMOs) either based on covalent SUMO modification (SUMOylation), or based on non-covalent SUMO interaction via SUMO interacting motifs (SIMs). We show here that the HPV16 L2 comprises at least one SIM, which is crucial for the L2 interaction with SUMO2 in immunoprecipitation and…
The Cytoskeletal Adaptor Obscurin-Like 1 Interacts with the Human Papillomavirus 16 (HPV16) Capsid Protein L2 and Is Required for HPV16 Endocytosis.
2016
ABSTRACT 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 no…
Human Papillomavirus Types 16, 18, and 31 Share Similar Endocytic Requirements for Entry
2013
ABSTRACT Human papillomavirus type 18 (HPV18), one of the HPVs with malignant potential, enters cells by an unknown endocytic mechanism. The key cellular requirements for HPV18 endocytosis were tested in comparison to those for HPV16 and -31 endocytoses. HPV18 (like HPV16 and -31) entry was independent of clathrin, caveolin, dynamin, and lipid rafts but required actin polymerization and tetraspanin CD151, and the viruses were routed to the same LAMP-1-positive compartment. Hence, the viruses shared similar cellular requirements for endocytic entry.
Identification of the dynein light chains required for human papillomavirus infection
2010
Summary Human papillomaviruses (HPVs) are a family of small non-enveloped DNA viruses. Some genital HPV types, including HPV type 16 (HPV16), are the causative agent for the development of cancer at the site of infection. HPVs encode two capsid proteins, L1 and L2. After endocytic cell entry and egress from endosomes, L2 accompanies the viral DNA to the nucleus where replication is initiated. For cytoplasmic transport, L2 interacts with the microtubule network via the motor protein complex dynein. We have performed yeast two-hybrid screening and identified the dynein light chain DYNLT1 (previously called Tctex1) as interaction partner of HPV16 L2. Using co-immunoprecipitation and immunofluo…
Tetraspanin CD63 controls basolateral sorting of organic cation transporter 2 in renal proximal tubules.
2016
CD63 is a ubiquitously expressed member of the tetraspanin superfamily. Using a mating-based split-ubiquitin-yeast 2-hybrid system, pull-down experiments, total internal reflection fluorescence microscopy, Forster resonance energy transfer, and biotinylation assays, we found that CD63 interacts with human organic cation transporter 2 (hOCT2), which transports endogenous and exogenous substrates, such as neurotransmitters and drugs in several epithelial cells. CD63 overexpression affects cellular localization of hOCT2 expressed in human embryonic kidney (HEK)293 cells. Studies with CD63-knockout mice indicate that in renal proximal tubules, CD63 determines the insertion of the mouse ortholog…
Tannins from Hamamelis virginiana Bark Extract: Characterization and Improvement of the Antiviral Efficacy against Influenza A Virus and Human Papill…
2014
Antiviral activity has been demonstrated for different tannin-rich plant extracts. Since tannins of different classes and molecular weights are often found together in plant extracts and may differ in their antiviral activity, we have compared the effect against influenza A virus (IAV) of Hamamelis virginiana L. bark extract, fractions enriched in tannins of different molecular weights and individual tannins of defined structures, including pseudotannins. We demonstrate antiviral activity of the bark extract against different IAV strains, including the recently emerged H7N9, and show for the first time that a tannin-rich extract inhibits human papillomavirus (HPV) type 16 infection. As the …
Identification of the Tetraspanin CD9 as an Interaction Partner of Organic Cation Transporters 1 and 2
2019
Organic cation transporters (OCTs) are membrane proteins with relevant physiological (because they accept neurotransmitters as substrate) and pharmacological (because of their interaction with drugs) roles. The human OCTs hOCT1 (SLC22A1/hOCT1) and hOCT2 (SLC22A2/hOCT2) are highly expressed in hepatic (hOCT1) and in renal and neuronal tissue (hOCT2), suggesting a possible role in modulating neurotransmitter activity in the liver, kidney, and brain, and their clearance from the blood. Even though there are several data demonstrating that OCTs are regulated under various patho-physiological conditions, it remains largely unknown which proteins directly interact with OCTs and thereby influence …
Polyethylenimine is a strong inhibitor of human papillomavirus and cytomegalovirus infection.
2012
ABSTRACT Polyethylenimines are cationic polymers with potential as delivery vectors in gene therapy and with proven antimicrobial activity. However, the antiviral activity of polyethylenimines has not been addressed in detail thus far. We have studied the inhibitory effects of a linear 25-kDa polyethylenimine on infections with human papillomaviruses and human cytomegaloviruses. Preincubation of cells with polyethylenimine blocked primary attachment of both viruses to cells, resulting in a significant reduction of infection. In addition, the dissemination of human cytomegalovirus in culture cells was efficiently reduced by recurrent administration of polyethylenimine. Polyethylenimine conce…
Clathrin- and Caveolin-Independent Entry of Human Papillomavirus Type 16—Involvement of Tetraspanin-Enriched Microdomains (TEMs)
2008
BACKGROUND: Infectious entry of human papillomaviruses into their host cells is an important step in the viral life cycle. For cell binding these viruses use proteoglycans as initial attachment sites. Subsequent transfer to a secondary receptor molecule seems to be involved in virus uptake. Depending on the papillomavirus subtype, it has been reported that entry occurs by clathrin- or caveolin-mediated mechanisms. Regarding human papillomavirus type 16 (HPV16), the primary etiologic agent for development of cervical cancer, clathrin-mediated endocytosis was described as infectious entry pathway. METHODOLOGY/PRINCIPAL FINDINGS: Using immunofluorescence and infection studies we show in contra…
Tetraspanin CD151 Mediates Papillomavirus Type 16 Endocytosis
2013
ABSTRACT Human papillomavirus type 16 (HPV16) is the primary etiologic agent for cervical cancer. The infectious entry of HPV16 into cells occurs via a so-far poorly characterized clathrin- and caveolin-independent endocytic pathway, which involves tetraspanin proteins and actin. In this study, we investigated the specific role of the tetraspanin CD151 in the early steps of HPV16 infection. We show that surface-bound HPV16 moves together with CD151 within the plane of the membrane before they cointernalize into endosomes. Depletion of endogenous CD151 did not affect binding of viral particles to cells but resulted in reduction of HPV16 endocytosis. HPV16 uptake is dependent on the C-termina…
DS_DISC859837 – Supplemental material for Identification of the Tetraspanin CD9 as an Interaction Partner of Organic Cation Transporters 1 and 2
2019
Supplemental material, DS_DISC859837 for Identification of the Tetraspanin CD9 as an Interaction Partner of Organic Cation Transporters 1 and 2 by Beatrice Snieder, Sabine Brast, Alexander Grabner, Sven Buchholz, Rita Schröter, Gilles A. Spoden, Luise Florin, Johanna Salomon, Tobias Albrecht, Vivien Barz, Alex Sparreboom and Giuliano Ciarimboli in SLAS Discovery