{"entity": "researcher", "timestamp": "2026-06-17T04:20:54.536Z", "family": "Lundmark", "given": "Richard", "initials": "R", "orcid": "0000-0001-9104-724X", "affiliations": ["Department of Integrative Medical Biology, Ume\u00e5 University, Ume\u00e5, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/3e1b756caa79468dab0f960e43cd61d3.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/3e1b756caa79468dab0f960e43cd61d3"}}, "publications": [{"entity": "publication", "iuid": "b05f9a8302e1405588f93dc3cb79e0e5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b05f9a8302e1405588f93dc3cb79e0e5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b05f9a8302e1405588f93dc3cb79e0e5"}}, "title": "Proviral NUP153 binding to viral proteins and RNA regulates structural-nonstructural protein ratios in orthoflavivirus infection.", "authors": [{"family": "Peters", "given": "Marie B A", "initials": "MBA", "orcid": "0000-0001-8994-0864", "researcher": {"href": "https://publications.scilifelab.se/researcher/df4733590d054742b732c2028a8f5e8a.json"}}, {"family": "Lindqvist", "given": "Richard", "initials": "R"}, {"family": "Kassa", "given": "Eszter", "initials": "E"}, {"family": "Yau", "given": "Wai-Lok", "initials": "WL"}, {"family": "Sengupta", "given": "Pallabi", "initials": "P", "orcid": "0000-0002-1413-9412", "researcher": {"href": "https://publications.scilifelab.se/researcher/851c95f648f242e0ba67202279725796.json"}}, {"family": "Niedermoser", "given": "Isabell", "initials": "I", "orcid": "0000-0002-5301-3361", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a2b5c11f4f945a5a273c9fd040bee6f.json"}}, {"family": "Gerold", "given": "Gisa", "initials": "G", "orcid": "0000-0002-1326-5038", "researcher": {"href": "https://publications.scilifelab.se/researcher/6353493de47c4ec58831f79ed94045f4.json"}}, {"family": "Sabouri", "given": "Nasim", "initials": "N", "orcid": "0000-0002-4541-7702", "researcher": {"href": "https://publications.scilifelab.se/researcher/4bdc688dc85a4932acfdfffad8bfc443.json"}}, {"family": "Ivarsson", "given": "Ylva", "initials": "Y", "orcid": "0000-0002-7081-3846", "researcher": {"href": "https://publications.scilifelab.se/researcher/f51534acce8c4214a55a3e7387850d53.json"}}, {"family": "Lundmark", "given": "Richard", "initials": "R", "orcid": "0000-0001-9104-724X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e1b756caa79468dab0f960e43cd61d3.json"}}, {"family": "\u00d6verby", "given": "Anna K", "initials": "AK", "orcid": "0000-0001-6553-0940", "researcher": {"href": "https://publications.scilifelab.se/researcher/506b0e2b2d884f868df73c7663b9ffb7.json"}}], "type": "journal article", "published": "2026-04-08", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723"}, "abstract": "Orthoflaviviruses are RNA viruses that cause serious diseases in humans, with currently no antivirals available. Targeting host factors is emerging as an attractive antiviral approach. However, as a first step, there is a need to understand which host proteins are hijacked and for what purpose. Here, using a combination of fluorescence microscopy, knock-down, crosslinking immunoprecipitation sequencing, mass spectrometry, and in vitro and biophysical assays, we identify nucleoporin-153 (NUP153) as a proviral factor during orthoflavivirus infection. We show that NUP153 is recruited to the virus amplification site on the endoplasmic reticulum to impact the structural to nonstructural viral protein ratios. We find that NUP153 interacts with both the viral proteins NS3 and NS5, and a highly conserved G-rich motif on the viral RNA. These interactions specifically promote the production of viral structural proteins, leading to an efficient virion assembly, virus release and spread to new cells. We propose that NUP153 acts as a key regulator in viral protein ratios, a mechanism that appears conserved among orthoflaviviruses.", "doi": "10.1038/s41467-026-71449-1", "pmid": "41951628", "labels": {"NGI Short read": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-026-71449-1"}], "notes": [], "created": "2026-04-10T12:13:07.525Z", "modified": "2026-04-10T12:13:08.280Z"}, {"entity": "publication", "iuid": "2425340e03244da090b07b7a32459592", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2425340e03244da090b07b7a32459592.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2425340e03244da090b07b7a32459592"}}, "title": "The ACBD3 protein coordinates ER-Golgi contacts to enable productive TBEV infection.", "authors": [{"family": "Yau", "given": "Wai-Lok", "initials": "W-L", "orcid": "0009-0007-0386-3919", "researcher": {"href": "https://publications.scilifelab.se/researcher/2044fb19cb8c4ecb94ddb6676da79a7d.json"}}, {"family": "Peters", "given": "Marie B A", "initials": "MBA"}, {"family": "R\u00f6nfeldt", "given": "Sebastian", "initials": "S"}, {"family": "Sorin", "given": "Marie N", "initials": "MN"}, {"family": "Lindqvist", "given": "Richard", "initials": "R"}, {"family": "Pulkkinen", "given": "Lauri I A", "initials": "LIA"}, {"family": "Carlson", "given": "Lars-Anders", "initials": "L-A"}, {"family": "\u00d6verby", "given": "Anna K", "initials": "AK", "orcid": "0000-0001-6553-0940", "researcher": {"href": "https://publications.scilifelab.se/researcher/506b0e2b2d884f868df73c7663b9ffb7.json"}}, {"family": "Lundmark", "given": "Richard", "initials": "R", "orcid": "0000-0001-9104-724X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e1b756caa79468dab0f960e43cd61d3.json"}}], "type": "journal article", "published": "2025-05-20", "journal": {"title": "J. Virol.", "issn": "1098-5514", "volume": "99", "issue": "5", "pages": "e0222424", "issn-l": "0022-538X"}, "abstract": "Flavivirus infection involves extensive remodeling of the endoplasmic reticulum (ER), which is key to both the replication of the viral RNA genome as well as the assembly and release of new virions. However, little is known about how viral proteins and host factors cooperatively facilitate such a vast transformation of the ER, and how this influences the different steps of the viral life cycle. In this study, we screened for host proteins that were enriched in close proximity to the tick-borne encephalitis virus (TBEV) protein NS4B and found that the top candidates were coupled to trafficking between ER exit sites (ERES) and the Golgi. We characterized the role of ACBD3, one of the identified proteins, and showed that it promotes TBEV infection. Depletion of ACBD3 inhibited virus replication and resulted in abnormal transformation of the ER, leading to reduced virion release. ACBD3's proviral mechanism did not involve the recruitment of PI4PK as previously described for enteroviruses. Instead, productive TBEV infection required the full-length ACBD3, which localizes to ER-Golgi contact sites together with NS4B. We propose that NS4B and ACBD3 promote replication by coordinating the transformation of the ER, which is required for RNA replication and particle release. The transformation involves direct coupling to the Golgi which facilitates efficient virion transport.\n\nFlaviviruses like tick-borne encephalitis have significant effects on human health. During flavivirus infection, the viral particles enter the host cells and transform the endoplasmic reticulum (ER), which is a membranous organelle and the main site of cellular protein synthesis. Although this is critical for successful infection, the details of the process are unknown. Here, we found that the viral protein NS4B and the host protein ACBD facilitate this transformation by ensuring that the ER is coupled to the Golgi apparatus, the organelle responsible for transporting material out of the cell. TBEV uses ACBD3 to guarantee that the connection sites between the transformed ER and the Golgi remain functional so that RNA is replicated and the produced viral particles are exported from the cell and can infect further cells. Our work sheds light both on the basic biology of flavivirus infection, and virus-induced remodeling of membranous organelles.", "doi": "10.1128/jvi.02224-24", "pmid": "40207930", "labels": {"Cryo-EM": "Service", "Integrated Microscopy Technologies Ume\u00e5": "Service", "Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12090792"}], "notes": [], "created": "2025-10-30T12:10:36.606Z", "modified": "2025-11-20T18:09:57.678Z"}, {"entity": "publication", "iuid": "3365d1fc9ac7482a996bbeb10f42de8e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3365d1fc9ac7482a996bbeb10f42de8e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3365d1fc9ac7482a996bbeb10f42de8e"}}, "title": "Cryo-electron tomography reveals coupled flavivirus replication, budding and maturation.", "authors": [{"family": "Dahmane", "given": "Selma", "initials": "S", "orcid": "0000-0003-4193-1496", "researcher": {"href": "https://publications.scilifelab.se/researcher/78124ba9dbac444aaee032c91c235a88.json"}}, {"family": "Schexnaydre", "given": "Erin", "initials": "E", "orcid": "0000-0002-2993-8647", "researcher": {"href": "https://publications.scilifelab.se/researcher/f643b7350ed5404aac418ce43d907f27.json"}}, {"family": "Zhang", "given": "Jianguo", "initials": "J", "orcid": "0000-0002-3784-6515", "researcher": {"href": "https://publications.scilifelab.se/researcher/3575f209f0d74bc1b8be39dd68d51fd3.json"}}, {"family": "Rosendal", "given": "Ebba", "initials": "E", "orcid": "0000-0001-8512-0535", "researcher": {"href": "https://publications.scilifelab.se/researcher/dda3f5ae552241eea145e011afdfad20.json"}}, {"family": "Chotiwan", "given": "Nunya", "initials": "N", "orcid": "0000-0003-3214-6605", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba9da05817a4a8ea7037131000d6a7f.json"}}, {"family": "Singh", "given": "Bina Kumari", "initials": "BK", "orcid": "0000-0002-9500-2759", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee00e03259f0463f84802861542cf940.json"}}, {"family": "Yau", "given": "Wai-Lok", "initials": "WL", "orcid": "0009-0007-0386-3919", "researcher": {"href": "https://publications.scilifelab.se/researcher/2044fb19cb8c4ecb94ddb6676da79a7d.json"}}, {"family": "Lundmark", "given": "Richard", "initials": "R", "orcid": "0000-0001-9104-724X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e1b756caa79468dab0f960e43cd61d3.json"}}, {"family": "Barad", "given": "Benjamin", "initials": "B", "orcid": "0000-0002-1016-862X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a118a58f2f140bab794786ac581d3ac.json"}}, {"family": "Grotjahn", "given": "Danielle A", "initials": "DA", "orcid": "0000-0001-5908-7882", "researcher": {"href": "https://publications.scilifelab.se/researcher/e9c2292eb2294f56bcc068a7a01737a8.json"}}, {"family": "Liese", "given": "Susanne", "initials": "S", "orcid": "0000-0001-7420-5488", "researcher": {"href": "https://publications.scilifelab.se/researcher/cb4ed3f41d6946e1a82472041e9a96d6.json"}}, {"family": "Carlson", "given": "Andreas", "initials": "A", "orcid": "0000-0002-3068-9983", "researcher": {"href": "https://publications.scilifelab.se/researcher/39f4cc3bec4747da984c7c382a8ca5ae.json"}}, {"family": "\u00d6verby", "given": "Anna K", "initials": "AK", "orcid": "0000-0001-6553-0940", "researcher": {"href": "https://publications.scilifelab.se/researcher/506b0e2b2d884f868df73c7663b9ffb7.json"}}, {"family": "Carlson", "given": "Lars-Anders", "initials": "LA", "orcid": "0000-0003-2342-6488", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba0e366ce21e49b48212bbed5a0a7bd1.json"}}], "type": "journal article", "published": "2024-10-21", "journal": {"title": "bioRxiv", "issn": "2692-8205", "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": "Flaviviruses replicate their genomes in replication organelles (ROs) formed as bud-like invaginations on the endoplasmic reticulum (ER) membrane, which also functions as the site for virion assembly. While this localization is well established, it is not known to what extent viral membrane remodeling, genome replication, virion assembly, and maturation are coordinated. Here, we imaged tick-borne flavivirus replication in human cells using cryo-electron tomography. We find that the RO membrane bud is shaped by a combination of a curvature-establishing coat and the pressure from intraluminal template RNA. A protein complex at the RO base extends to an adjacent membrane, where immature virions bud. Naturally occurring furin site variants determine whether virions mature in the immediate vicinity of ROs. We further visualize replication in mouse brain tissue by cryo-electron tomography. Taken together, these findings reveal a close spatial coupling of flavivirus genome replication, budding, and maturation.", "doi": "10.1101/2024.10.13.618056", "pmid": "39416041", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11482891"}, {"db": "pii", "key": "2024.10.13.618056"}], "notes": [], "created": "2025-10-29T14:50:30.370Z", "modified": "2025-10-29T14:55:33.629Z"}, {"entity": "publication", "iuid": "a447f029992d4e928ce3e5b703f1cda2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a447f029992d4e928ce3e5b703f1cda2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a447f029992d4e928ce3e5b703f1cda2"}}, "title": "Dynamin2 functions as an accessory protein to reduce the rate of caveola internalization.", "authors": [{"family": "Larsson", "given": "Elin", "initials": "E", "orcid": "0000-0003-4224-8226", "researcher": {"href": "https://publications.scilifelab.se/researcher/c85534a046a4475b93a04bc59537e4d6.json"}}, {"family": "Mor\u00e9n", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0002-4252-6903", "researcher": {"href": "https://publications.scilifelab.se/researcher/582b56871a184c7aa81939b4a6111717.json"}}, {"family": "McMahon", "given": "Kerrie-Ann", "initials": "KA", "orcid": "0000-0002-0833-5708", "researcher": {"href": "https://publications.scilifelab.se/researcher/8231b13620dc48ba869ce529131805fa.json"}}, {"family": "Parton", "given": "Robert G", "initials": "RG", "orcid": "0000-0002-7494-5248", "researcher": {"href": "https://publications.scilifelab.se/researcher/499570ab993a4d0991e93597dc82f32e.json"}}, {"family": "Lundmark", "given": "Richard", "initials": "R", "orcid": "0000-0001-9104-724X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e1b756caa79468dab0f960e43cd61d3.json"}}], "type": "journal article", "published": "2023-04-03", "journal": {"title": "J. Cell Biol.", "issn": "1540-8140", "volume": "222", "issue": "4", "issn-l": "0021-9525"}, "abstract": "Caveolae are small membrane invaginations that generally are stably attached to the plasma membrane. Their release is believed to depend on the GTPase dynamin 2 (Dyn2), in analogy with its role in fission of clathrin-coated vesicles. The mechanistic understanding of caveola fission is, however, sparse. Here, we used microscopy-based tracking of individual caveolae in living cells to determine the role of Dyn2 in caveola dynamics. We report that Dyn2 stably associated with the bulb of a subset of caveolae, but was not required for formation or fission of caveolae. Dyn2-positive caveolae displayed longer plasma membrane duration times, whereas depletion of Dyn2 resulted in shorter duration times and increased caveola fission. The stabilizing role of Dyn2 was independent of its GTPase activity and the caveola stabilizing protein EHD2. Thus, we propose that, in contrast to the current view, Dyn2 is not a core component of the caveolae machinery, but rather functions as an accessory protein that restrains caveola internalization.", "doi": "10.1083/jcb.202205122", "pmid": "36729022", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9929934"}, {"db": "pii", "key": "213853"}], "notes": [], "created": "2023-03-08T09:41:00.089Z", "modified": "2023-03-08T09:41:00.538Z"}, {"entity": "publication", "iuid": "3a155e54460049e4aaec26f48262277f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3a155e54460049e4aaec26f48262277f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3a155e54460049e4aaec26f48262277f"}}, "title": "Membrane insertion mechanism of the caveola coat protein Cavin1.", "authors": [{"family": "Liu", "given": "Kang-Cheng", "initials": "KC"}, {"family": "Pace", "given": "Hudson", "initials": "H"}, {"family": "Larsson", "given": "Elin", "initials": "E"}, {"family": "Hossain", "given": "Shakhawath", "initials": "S", "orcid": "0000-0001-9556-2695", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ca81ff3e4f84f9cbdeffe0b803d8a0c.json"}}, {"family": "Kabedev", "given": "Aleksei", "initials": "A", "orcid": "0000-0003-3429-3713", "researcher": {"href": "https://publications.scilifelab.se/researcher/e624e3f5fb13454296e35755f02cf693.json"}}, {"family": "Shukla", "given": "Ankita", "initials": "A", "orcid": "0000-0003-2824-2709", "researcher": {"href": "https://publications.scilifelab.se/researcher/f232904e8ef046ec87fb86ea95430bd1.json"}}, {"family": "Jerschabek", "given": "Vanessa", "initials": "V"}, {"family": "Mohan", "given": "Jagan", "initials": "J"}, {"family": "Bergstr\u00f6m", "given": "Christel A S", "initials": "CAS"}, {"family": "Bally", "given": "Marta", "initials": "M", "orcid": "0000-0002-5865-8302", "researcher": {"href": "https://publications.scilifelab.se/researcher/923521b36e7746a3979801d0502eb6a9.json"}}, {"family": "Schwieger", "given": "Christian", "initials": "C", "orcid": "0000-0001-8327-1233", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b495d6a11134588b5f2be725d72ed56.json"}}, {"family": "Hubert", "given": "Madlen", "initials": "M", "orcid": "0000-0002-5908-9535", "researcher": {"href": "https://publications.scilifelab.se/researcher/48acd1c7795b45919bba57a5a9817ea7.json"}}, {"family": "Lundmark", "given": "Richard", "initials": "R", "orcid": "0000-0001-9104-724X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e1b756caa79468dab0f960e43cd61d3.json"}}], "type": "journal article", "published": "2022-06-21", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "119", "issue": "25", "pages": "e2202295119", "issn-l": "0027-8424"}, "abstract": "Caveolae are small plasma membrane invaginations, important for control of membrane tension, signaling cascades, and lipid sorting. The caveola coat protein Cavin1 is essential for shaping such high curvature membrane structures. Yet, a mechanistic understanding of how Cavin1 assembles at the membrane interface is lacking. Here, we used model membranes combined with biophysical dissection and computational modeling to show that Cavin1 inserts into membranes. We establish that initial phosphatidylinositol (4, 5) bisphosphate [PI(4,5)P2]-dependent membrane adsorption of the trimeric helical region 1 (HR1) of Cavin1 mediates the subsequent partial separation and membrane insertion of the individual helices. Insertion kinetics of HR1 is further enhanced by the presence of flanking negatively charged disordered regions, which was found important for the coassembly of Cavin1 with Caveolin1 in living cells. We propose that this intricate mechanism potentiates membrane curvature generation and facilitates dynamic rounds of assembly and disassembly of Cavin1 at the membrane.", "doi": "10.1073/pnas.2202295119", "pmid": "35696574", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9231606"}], "notes": [], "created": "2022-11-09T15:49:41.053Z", "modified": "2024-01-16T13:48:36.114Z"}, {"entity": "publication", "iuid": "112965c0f79145bb91da7dfa37d0dd1f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/112965c0f79145bb91da7dfa37d0dd1f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/112965c0f79145bb91da7dfa37d0dd1f"}}, "title": "Lipid accumulation controls the balance between surface connection and scission of caveolae.", "authors": [{"family": "Hubert", "given": "Madlen", "initials": "M"}, {"family": "Larsson", "given": "Elin", "initials": "E"}, {"family": "Vegesna", "given": "Naga Venkata Gayathri", "initials": "NVG"}, {"family": "Ahnlund", "given": "Maria", "initials": "M"}, {"family": "Johansson", "given": "Annika I", "initials": "AI", "orcid": "0000-0001-5000-1288", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b0835b94db946929c1cb0c8f9319068.json"}}, {"family": "Moodie", "given": "Lindon Wk", "initials": "LW"}, {"family": "Lundmark", "given": "Richard", "initials": "R", "orcid": "0000-0001-9104-724X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e1b756caa79468dab0f960e43cd61d3.json"}}], "type": "comparative study", "published": "2020-05-04", "journal": {"title": "Elife", "issn": "2050-084X", "issn-l": "2050-084X", "volume": "9", "issue": null, "pages": null}, "abstract": "Caveolae are bulb-shaped invaginations of the plasma membrane (PM) that undergo scission and fusion at the cell surface and are enriched in specific lipids. However, the influence of lipid composition on caveolae surface stability is not well described or understood. Accordingly, we inserted specific lipids into the cell PM via membrane fusion and studied their acute effects on caveolae dynamics. We demonstrate that sphingomyelin stabilizes caveolae to the cell surface, whereas cholesterol and glycosphingolipids drive caveolae scission from the PM. Although all three lipids accumulated specifically in caveolae, cholesterol and sphingomyelin were actively sequestered, whereas glycosphingolipids diffused freely. The ATPase EHD2 restricts lipid diffusion and counteracts lipid-induced scission. We propose that specific lipid accumulation in caveolae generates an intrinsically unstable domain prone to scission if not restrained by EHD2 at the caveolae neck. This work provides a mechanistic link between caveolae and their ability to sense the PM lipid composition.", "doi": "10.7554/eLife.55038", "pmid": "32364496", "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Collaborative", "Swedish Metabolomics Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "55038"}, {"db": "pmc", "key": "PMC7239661"}], "notes": [], "created": "2020-12-11T12:02:15.906Z", "modified": "2025-10-17T13:03:16.859Z"}, {"entity": "publication", "iuid": "d9748ddcdd2c4bf9b89662bb4627add9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d9748ddcdd2c4bf9b89662bb4627add9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d9748ddcdd2c4bf9b89662bb4627add9"}}, "title": "Model System for the Formation of Tick-Borne Encephalitis Virus Replication Compartments without Viral RNA Replication.", "authors": [{"family": "Yau", "given": "Wai-Lok", "initials": "WL"}, {"family": "Nguyen-Dinh", "given": "Van", "initials": "V"}, {"family": "Larsson", "given": "Elin", "initials": "E"}, {"family": "Lindqvist", "given": "Richard", "initials": "R"}, {"family": "\u00d6verby", "given": "Anna K", "initials": "AK", "orcid": "0000-0001-6553-0940", "researcher": {"href": "https://publications.scilifelab.se/researcher/506b0e2b2d884f868df73c7663b9ffb7.json"}}, {"family": "Lundmark", "given": "Richard", "initials": "R", "orcid": "0000-0001-9104-724X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e1b756caa79468dab0f960e43cd61d3.json"}}], "type": "journal article", "published": "2019-09-15", "journal": {"volume": "93", "issn": "1098-5514", "issue": "18", "pages": null, "title": "J. Virol.", "issn-l": "0022-538X"}, "abstract": "Flavivirus is a positive-sense, single-stranded RNA viral genus, with members causing severe diseases in humans such as tick-borne encephalitis, yellow fever, and dengue fever. Flaviviruses are known to cause remodeling of intracellular membranes into small cavities, where replication of the viral RNA takes place. Nonstructural (NS) proteins are not part of the virus coat and are thought to participate in the formation of these viral replication compartments (RCs). Here, we used tick-borne encephalitis virus (TBEV) as a model for the flaviviruses and developed a stable human cell line in which the expression of NS proteins can be induced without viral RNA replication. The model system described provides a novel and benign tool for studies of the viral components under controlled expression levels. We show that the expression of six NS proteins is sufficient to induce infection-like dilation of the endoplasmic reticulum (ER) and the formation of RC-like membrane invaginations. The NS proteins form a membrane-associated complex in the ER, and electron tomography reveals that the dilated areas of the ER are closely associated with lipid droplets and mitochondria. We propose that the NS proteins drive the remodeling of ER membranes and that viral RNA, RNA replication, viral polymerase, and TBEV structural proteins are not required.IMPORTANCE TBEV infection causes a broad spectrum of symptoms, ranging from mild fever to severe encephalitis. Similar to other flaviviruses, TBEV exploits intracellular membranes to build RCs for viral replication. The viral NS proteins have been suggested to be involved in this process; however, the mechanism of RC formation and the roles of individual NS proteins remain unclear. To study how TBEV induces membrane remodeling, we developed an inducible stable cell system expressing the TBEV NS polyprotein in the absence of viral RNA replication. Using this system, we were able to reproduce RC-like vesicles that resembled the RCs formed in flavivirus-infected cells, in terms of morphology and size. This cell system is a robust tool to facilitate studies of flavivirus RC formation and is an ideal model for the screening of antiviral agents at a lower biosafety level.", "doi": "10.1128/JVI.00292-19", "pmid": "31243132", "labels": {"Cryo-EM": "Service", "Integrated Microscopy Technologies Ume\u00e5": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "JVI.00292-19"}, {"db": "pmc", "key": "PMC6714791"}], "notes": [], "created": "2020-01-08T09:05:19.109Z", "modified": "2024-01-16T13:48:43.870Z"}, {"entity": "publication", "iuid": "085fe36254ea4ac48b90a73f69608482", "links": {"self": {"href": "https://publications.scilifelab.se/publication/085fe36254ea4ac48b90a73f69608482.json"}, "display": {"href": "https://publications.scilifelab.se/publication/085fe36254ea4ac48b90a73f69608482"}}, "title": "Photoactivated Colibactin Probes Induce Cellular DNA Damage.", "authors": [{"family": "Moodie", "given": "Lindon W K", "initials": "LWK", "orcid": "0000-0002-9500-4535", "researcher": {"href": "https://publications.scilifelab.se/researcher/d9377be68ffc416690153f44ab45de21.json"}}, {"family": "Hubert", "given": "Madlen", "initials": "M"}, {"family": "Zhou", "given": "Xin", "initials": "X"}, {"family": "Albers", "given": "Michael F", "initials": "MF"}, {"family": "Lundmark", "given": "Richard", "initials": "R", "orcid": "0000-0001-9104-724X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e1b756caa79468dab0f960e43cd61d3.json"}}, {"family": "Wanrooij", "given": "Sjoerd", "initials": "S", "orcid": "0000-0001-6126-4382", "researcher": {"href": "https://publications.scilifelab.se/researcher/84c9ac1e1b8f4cf68ae25766bc8dfa0e.json"}}, {"family": "Hedberg", "given": "Christian", "initials": "C", "orcid": "0000-0002-0832-8276", "researcher": {"href": "https://publications.scilifelab.se/researcher/1340d53342924ebcaf8de25ea64650b4.json"}}], "type": "journal article", "published": "2019-01-28", "journal": {"volume": "58", "issn": "1521-3773", "issue": "5", "pages": "1417-1421", "title": "Angew. Chem. Int. Ed. Engl.", "issn-l": "1433-7851"}, "abstract": "Colibactin is a small molecule produced by certain bacterial species of the human microbiota that harbour the pks genomic island. Pks + bacteria induce a genotoxic phenotype in eukaryotic cells and have been linked with colorectal cancer progression. Colibactin is produced in a benign, prodrug form which, prior to export, is enzymatically matured by the producing bacteria to its active form. Although the complete structure of colibactin has not been determined, key structural features have been described including an electrophilic cyclopropane motif, which is believed to alkylate DNA. To investigate the influence of the putative \"warhead\" and the prodrug strategy on genotoxicity, a series of photolabile colibactin probes were prepared that upon irradiation induced a pks+ like phenotype in HeLa cells. Furthermore, results from DNA cross-linking and imaging studies of clickable analogues enforce the hypothesis that colibactin effects its genotoxicity by directly targeting DNA.", "doi": "10.1002/anie.201812326", "pmid": "30506956", "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Service"}, "xrefs": [], "notes": [], "created": "2020-02-12T14:06:26.224Z", "modified": "2021-06-21T13:40:51.208Z"}, {"entity": "publication", "iuid": "1efc9e8a5f12496091a749b6a455d5b0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1efc9e8a5f12496091a749b6a455d5b0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1efc9e8a5f12496091a749b6a455d5b0"}}, "title": "Endocytic turnover of Rab8 controls cell polarization.", "authors": [{"family": "Vidal-Quadras", "given": "Maite", "initials": "M"}, {"family": "Holst", "given": "Mikkel R", "initials": "MR"}, {"family": "Francis", "given": "Monika K", "initials": "MK", "orcid": "0000-0002-6806-0515", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbfa343ff09d4e7095fced73be91df51.json"}}, {"family": "Larsson", "given": "Elin", "initials": "E"}, {"family": "Hachimi", "given": "Mariam", "initials": "M"}, {"family": "Yau", "given": "Wai-Lok", "initials": "WL"}, {"family": "Per\u00e4nen", "given": "Johan", "initials": "J"}, {"family": "Mart\u00edn-Belmonte", "given": "Fernando", "initials": "F"}, {"family": "Lundmark", "given": "Richard", "initials": "R", "orcid": "0000-0001-9104-724X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e1b756caa79468dab0f960e43cd61d3.json"}}], "type": "journal article", "published": "2017-03-15", "journal": {"title": "J. Cell. Sci.", "issn": "1477-9137", "volume": "130", "issue": "6", "pages": "1147-1157", "issn-l": "0021-9533"}, "abstract": "Adaptation of cell shape and polarization through the formation and retraction of cellular protrusions requires balancing of endocytosis and exocytosis combined with fine-tuning of the local activity of small GTPases like Rab8. Here, we show that endocytic turnover of the plasma membrane at protrusions is directly coupled to surface removal and inactivation of Rab8. Removal is induced by reduced membrane tension and mediated by the GTPase regulator associated with focal adhesion kinase-1 (GRAF1, also known as ARHGAP26), a regulator of clathrin-independent endocytosis. GRAF1-depleted cells were deficient in multi-directional spreading and displayed elevated levels of GTP-loaded Rab8, which was accumulated at the tips of static protrusions. Furthermore, GRAF1 depletion impaired lumen formation and spindle orientation in a 3D cell culture system, indicating that GRAF1 activity regulates polarity establishment. Our data suggest that GRAF1-mediated removal of Rab8 from the cell surface restricts its activity during protrusion formation, thereby facilitating dynamic adjustment of the polarity axis.", "doi": "10.1242/jcs.195420", "pmid": "28137756", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "jcs.195420"}, {"db": "pmc", "key": "PMC5358338"}], "notes": [], "created": "2020-01-23T16:36:50.803Z", "modified": "2021-06-21T15:44:32.527Z"}]}