{"entity": "journal", "iuid": "8465c8ae5cf04623af7e4ba6b4206a05", "timestamp": "2026-07-11T13:53:30.980Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/J.%20Virol..json"}, "display": {"href": "https://publications.scilifelab.se/journal/J.%20Virol."}}, "title": "J. Virol.", "issn": "1098-5514", "issn-l": "0022-538X", "publications_count": 8, "publications": [{"entity": "publication", "iuid": "467584c1e0774aef801f14804cc86726", "links": {"self": {"href": "https://publications.scilifelab.se/publication/467584c1e0774aef801f14804cc86726.json"}, "display": {"href": "https://publications.scilifelab.se/publication/467584c1e0774aef801f14804cc86726"}}, "title": "Influence of the pre-membrane and envelope proteins on structure, pathogenicity, and tropism of tick-borne encephalitis virus.", "authors": [{"family": "Rosendal", "given": "Ebba", "initials": "E", "orcid": "0000-0001-8512-0535", "researcher": {"href": "https://publications.scilifelab.se/researcher/dda3f5ae552241eea145e011afdfad20.json"}}, {"family": "Bisikalo", "given": "Kyrylo", "initials": "K"}, {"family": "Willekens", "given": "Stefanie M A", "initials": "SMA"}, {"family": "Lindgren", "given": "Marie", "initials": "M"}, {"family": "Holoubek", "given": "Ji\u0159\u00ed", "initials": "J"}, {"family": "Svoboda", "given": "Pavel", "initials": "P"}, {"family": "Lappalainen", "given": "Amanda", "initials": "A"}, {"family": "K\u00f6nighofer", "given": "Ebba", "initials": "E"}, {"family": "Mirgorodskaya", "given": "Ekaterina", "initials": "E"}, {"family": "Nord\u00e9n", "given": "Rickard", "initials": "R"}, {"family": "Morini", "given": "Federico", "initials": "F"}, {"family": "Rosenbaum", "given": "William", "initials": "W"}, {"family": "R\u016f\u017eek", "given": "Daniel", "initials": "D"}, {"family": "Ahlgren", "given": "Ulf", "initials": "U"}, {"family": "Anastasina", "given": "Maria", "initials": "M"}, {"family": "Merits", "given": "Andres", "initials": "A", "orcid": "0000-0001-8193-0071", "researcher": {"href": "https://publications.scilifelab.se/researcher/f77e550339464de88e94f9aa9a91e324.json"}}, {"family": "Butcher", "given": "Sarah J", "initials": "SJ", "orcid": "0000-0001-7060-5871", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7076e70172b45d7ab9de4ab86775ae9.json"}}, {"family": "Nilsson", "given": "Emma", "initials": "E"}, {"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": "2025-09-23", "journal": {"title": "J. Virol.", "issn": "1098-5514", "volume": "99", "issue": "9", "pages": "e0087025", "issn-l": "0022-538X"}, "abstract": "Tick-borne encephalitis virus (TBEV) is a neurotropic flavivirus that causes thousands of human infections annually. Viral tropism in the brain is determined by the presence of necessary receptors, entry factors, and the ability of the virus to overcome host defenses. The viral structural proteins, pre-membrane (prM), and envelope (E) play an important role in receptor binding, membrane fusion, particle maturation, and antibody neutralization. To understand how these proteins influence virus distribution and tropism in the brain, we generated a chimeric virus harboring the prM and ectodomain of E from TBEV in the background of the low-pathogenic Langat virus (LGTV). We solved the atomic structures of both the chimeric virus and LGTV to compare them to the known TBEV structure. We show that this chimeric virus remains low-pathogenic, while being structurally and antigenically similar to TBEV. Using 3D optical whole brain imaging combined with immunohistochemistry, we found that both LGTV and the chimeric virus primarily infect the cerebral cortex, with no significant differences in their localization or tropism. In contrast, TBEV shows high infection of the cerebellum and a strong preference toward Purkinje cells, indicating that factors other than the prM and E proteins are important for determining TBEV tropism in the brain. Together, this provides new insights into the roles of the structural and non-structural proteins of tick-borne flaviviruses.\n\nAlthough an effective vaccine exists, there is no treatment for those infected by the tick-borne encephalitis virus (TBEV). This study aimed to better understand how the virus's surface proteins influence viral tropism and pathogenicity. We created a chimeric virus with prM and E proteins of TBEV in the genetic background of the low-pathogenic Langat virus (LGTV). The chimeric virus remained low pathogenic, similar to LGTV. Both viruses infected similar brain regions, while TBEV showed a strong preference for the cerebellum and Purkinje cells. This means that other parts of the virus, such as non-structural proteins or NCR, likely decide how the virus behaves in the brain. This study also presents the first cryogenic electron microscopy structure of LGTV, the first whole-brain imaging of TBEV infection in mouse brain, and a new model system to study surface proteins in tick-borne flaviviruses-laying groundwork for future studies on viral tropism, antibody cross-reactivity, and virus-receptor interaction.", "doi": "10.1128/jvi.00870-25", "pmid": "40827915", "labels": {"Glycoproteomics and MS Proteomics": "Collaborative", "Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12456022"}], "notes": [], "created": "2025-10-22T19:22:15.679Z", "modified": "2025-11-13T09:31:25.575Z"}, {"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": "15fcc6be822e4aa68cd5cbc970867939", "links": {"self": {"href": "https://publications.scilifelab.se/publication/15fcc6be822e4aa68cd5cbc970867939.json"}, "display": {"href": "https://publications.scilifelab.se/publication/15fcc6be822e4aa68cd5cbc970867939"}}, "title": "Structure of the T=13 capsid of infectious pancreatic necrosis virus (IPNV)-a salmonid birnavirus.", "authors": [{"family": "Munke", "given": "Anna", "initials": "A", "orcid": "0000-0002-5510-2245", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fd6d8030171420190aa65f3eb1ac4bd.json"}}, {"family": "Ahmed Abdelrahim Gamil", "given": "Amr", "initials": "A"}, {"family": "Mikalsen", "given": "Aase B", "initials": "AB", "orcid": "0000-0001-6367-9629", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3f7fbaf8774430ba38bb79a66e40a77.json"}}, {"family": "Wang", "given": "Han", "initials": "H"}, {"family": "Evensen", "given": "\u00d8ystein", "initials": "\u00d8", "orcid": "0000-0003-3538-3657", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd35b9aea23f463787ed9a78ae800906.json"}}, {"family": "Okamoto", "given": "Kenta", "initials": "K", "orcid": "0000-0002-4858-1196", "researcher": {"href": "https://publications.scilifelab.se/researcher/9302e76f16a04afdbb72f00c805bffa4.json"}}], "type": "journal article", "published": "2025-02-25", "journal": {"title": "J. Virol.", "issn": "1098-5514", "pages": "e0145424", "volume": "99", "issue": "2", "issn-l": "0022-538X"}, "abstract": "Birnaviruses infect a broad range of vertebrate hosts, including fish and birds, and cause substantial economic losses in the fishery and livestock industries. The infectious pancreatic necrosis virus (IPNV), an aquabirnavirus, specifically infects salmonids. While structures on T=1 subviral particles of the birnaviruses, including IPNV, have been studied, structural insights into the infectious T=13 particles have been limited to the infectious bursal disease virus (IBDV), an avibirnavirus. Determining the capsid structure of the T=13 particle of IPNV is crucial for advancing knowledge of its antigenicity, capsid assembly, and possible functional structures. Here, the capsid structure of the IPNV L5 strain has been determined at a resolution of 2.75 \u00c5. The overall structure resembles the T=13 IBDV structure, with notable differences in the surface loops on the P domain of the VP2 capsid protein essential for antigenicity and virulence. Additionally, previously undescribed structural features have been identified, including the C-terminal regions of the VP2 subunits within the pentagonal assembly unit at each 5-fold axis, which interlock with adjacent VP2 subunits. This interlocking, together with class-averaged projections of triangular and pentagonal units, suggests that the pentagonal unit formation could be important for a correct T=13 particle assembly, preventing the formation of T=1 subviral particles. Furthermore, positively charged residues in obstructed capsid pores at each 5-fold axis are speculated to facilitate intraparticle genome synthesis of IPNV.IMPORTANCEAquabirnaviruses cause deadly infectious diseases in salmonid fish, posing significant challenges for both wild and farmed fish populations. The most prevalent aquabirnavirus worldwide is the infectious pancreatic necrosis virus, whose multifunctional capsid is critical to its infection, replication, and maturation. Previously, research has focused on the structure of the virus' non-infectious subviral capsid. In this study, however, the first structure of the large, infectious, and functional form of the capsid has been determined. This new capsid structure reveals functional motifs that were previously unclear in the non-infectious capsid. These motifs are believed to be essential for the virus' replication and particle assembly, making them promising targets for developing strategies to control virus proliferation.", "doi": "10.1128/jvi.01454-24", "pmid": "39817769", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11853034"}], "notes": [], "created": "2025-01-20T09:02:04.842Z", "modified": "2025-11-13T10:40:54.346Z"}, {"entity": "publication", "iuid": "350219f82d404eac946e2608b61d2b2d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/350219f82d404eac946e2608b61d2b2d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/350219f82d404eac946e2608b61d2b2d"}}, "title": "Human AdV-20-42-42, a Promising Novel Adenoviral Vector for Gene Therapy and Vaccine Product Development.", "authors": [{"family": "Ballmann", "given": "M\u00f3nika Z", "initials": "MZ"}, {"family": "Raus", "given": "Svjetlana", "initials": "S"}, {"family": "Engelhart", "given": "Ruben", "initials": "R"}, {"family": "Kaj\u00e1n", "given": "Gy\u0151z\u0151 L", "initials": "GL"}, {"family": "Beqqali", "given": "Abdelaziz", "initials": "A"}, {"family": "Hadoke", "given": "Patrick W F", "initials": "PWF"}, {"family": "van der Zalm", "given": "Chantal", "initials": "C"}, {"family": "Papp", "given": "Tibor", "initials": "T"}, {"family": "John", "given": "Lijo", "initials": "L"}, {"family": "Khan", "given": "Selina", "initials": "S"}, {"family": "Boedhoe", "given": "Satish", "initials": "S"}, {"family": "Danskog", "given": "Katarina", "initials": "K"}, {"family": "Fr\u00e4ngsmyr", "given": "Lars", "initials": "L"}, {"family": "Custers", "given": "Jerome", "initials": "J"}, {"family": "Bakker", "given": "Wilfried A M", "initials": "WAM", "orcid": "0000-0001-8731-6689", "researcher": {"href": "https://publications.scilifelab.se/researcher/0705915bcd1645dea78d781280a55854.json"}}, {"family": "van der Schaar", "given": "Hilde M", "initials": "HM"}, {"family": "Arnberg", "given": "Niklas", "initials": "N"}, {"family": "Lemckert", "given": "Angelique A C", "initials": "AAC"}, {"family": "Havenga", "given": "Menzo", "initials": "M"}, {"family": "Baker", "given": "Andrew H", "initials": "AH", "orcid": "0000-0003-1441-5576", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa8e8281602342e1906459c5c8df4fe6.json"}}], "type": "journal article", "published": "2021-10-27", "journal": {"title": "J. Virol.", "issn": "1098-5514", "volume": "95", "issue": "22", "pages": "e0038721", "issn-l": "0022-538X"}, "abstract": "Preexisting immune responses toward adenoviral vectors limit the use of a vector based on particular serotypes and its clinical applicability for gene therapy and/or vaccination. Therefore, there is a significant interest in vectorizing novel adenoviral types that have low seroprevalence in the human population. Here, we describe the discovery and vectorization of a chimeric human adenovirus, which we call HAdV-20-42-42. Full-genome sequencing revealed that this virus is closely related to human serotype 42, except for the penton base, which is derived from serotype 20. The HAdV-20-42-42 vector could be propagated stably to high titers on existing E1-complementing packaging cell lines. Receptor-binding studies revealed that the vector utilized both CAR and CD46 as receptors for cell entry. Furthermore, the HAdV-20-42-42 vector was potent in transducing human and murine cardiovascular cells and tissues, irrespective of the presence of blood coagulation factor X. In vivo characterizations demonstrate that when delivered intravenously (i.v.) in mice, HAdV-20-42-42 mainly targeted the lungs, liver, and spleen and triggered robust inflammatory immune responses. Finally, we demonstrate that potent T-cell responses against vector-delivered antigens could be induced upon intramuscular vaccination in mice. In summary, from the data obtained we conclude that HAdV-20-42-42 provides a valuable addition to the portfolio of adenoviral vectors available to develop efficacious products in the fields of gene therapy and vaccination. IMPORTANCE Adenoviral vectors are under investigation for a broad range of therapeutic indications in diverse fields, such as oncology and gene therapy, as well as for vaccination both for human and veterinary use. A wealth of data shows that preexisting immune responses may limit the use of a vector. Particularly in the current climate of global pandemic, there is a need to expand the toolbox with novel adenoviral vectors for vaccine development. Our data demonstrate that we have successfully vectorized a novel adenovirus type candidate with low seroprevalence. The cell transduction data and antigen-specific immune responses induced in vivo demonstrate that this vector is highly promising for the development of gene therapy and vaccine products.", "doi": "10.1128/JVI.00387-21", "pmid": "34469243", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8549523"}], "notes": [], "created": "2021-11-24T13:30:33.454Z", "modified": "2021-11-24T13:30:33.542Z"}, {"entity": "publication", "iuid": "d505916802d745ffaee823c537c2cad6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d505916802d745ffaee823c537c2cad6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d505916802d745ffaee823c537c2cad6"}}, "title": "The Human Adenovirus Type 2 Transcriptome: An Amazing Complexity of Alternatively Spliced mRNAs.", "authors": [{"family": "Westergren Jakobsson", "given": "Amanda", "initials": "A"}, {"family": "Segerman", "given": "Bo", "initials": "B"}, {"family": "Wallerman", "given": "Ola", "initials": "O"}, {"family": "Lind", "given": "Sara Bergstr\u00f6m", "initials": "SB"}, {"family": "Zhao", "given": "Hongxing", "initials": "H"}, {"family": "Rubin", "given": "Carl-Johan", "initials": "CJ"}, {"family": "Pettersson", "given": "Ulf", "initials": "U"}, {"family": "Akusj\u00e4rvi", "given": "G\u00f6ran", "initials": "G", "orcid": "0000-0003-2961-5060", "researcher": {"href": "https://publications.scilifelab.se/researcher/e61349b53aba497288dd44f3e643fdf8.json"}}], "type": "journal article", "published": "2020-11-25", "journal": {"title": "J. Virol.", "issn": "1098-5514", "issn-l": "0022-538X"}, "abstract": "We have used the Nanopore long-read sequencing platform to demonstrate how amazingly complex the human adenovirus type 2 (Ad2) transcriptome is with a flexible splicing machinery producing a range of novel mRNAs both from the early and late transcription units. In total we report more than 900 alternatively spliced mRNAs produced from the Ad2 transcriptome whereof more than 850 are novel mRNAs. A surprising finding was that more than 50% of all E1A transcripts extended upstream of the previously defined transcriptional start site. The novel start sites mapped close to the inverted terminal repeat (ITR) and within the E1A enhancer region. We speculate that novel promoters or enhancer driven transcription, so-called eRNA transcription, is responsible for producing these novel mRNAs. Their existence was verified by a peptide in the Ad2 proteome that was unique for the E1A ITR mRNA. Although we show a high complexity of alternative splicing from most early and late regions, the E3 region was by far the most complex when expressed at late times of infection. More than 400 alternatively spliced mRNAs were observed in this region alone. These mRNAs included extended L4 mRNAs containing E3 and L5 sequences and readthrough mRNAs combining E3 and L5 sequences. Our findings demonstrate that the virus has a remarkable capacity to produce novel exon combinations, which will offer the virus an evolutionary advantage to change the gene expression repertoire and protein production in an evolving environment.IMPORTANCE Work in the adenovirus system led to the groundbreaking discovery of RNA splicing and alternative RNA splicing in 1977. These mechanisms are essential in mammalian evolution by increasing the coding capacity of a genome. Here, we have used a long-read sequencing technology to characterize the complexity of human adenovirus pre-mRNA splicing in detail. It is mindboggling that the viral genome, which only houses around 36,000 bp, not being much larger than a single cellular gene, generates more than 900 alternatively spliced mRNAs. Recently, adenoviruses have been used as the backbone in several promising SARS-CoV-2 vaccines. Further improvement of adenovirus-based vaccines demands that the virus can be tamed into an innocent carrier of foreign genes. This requires a full understanding of the components that govern adenovirus replication and gene expression.", "doi": "10.1128/JVI.01869-20", "pmid": "33239457", "labels": {"Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "JVI.01869-20"}, {"db": "pmc", "key": "PMC7851563"}], "notes": [], "created": "2021-12-02T14:21:44.993Z", "modified": "2021-12-02T14:21:45.035Z"}, {"entity": "publication", "iuid": "b330828d9ccb481c88ca0ae89faaa9b1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b330828d9ccb481c88ca0ae89faaa9b1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b330828d9ccb481c88ca0ae89faaa9b1"}}, "title": "Capsid Structure of a Marine Algal Virus of the Order Picornavirales.", "authors": [{"family": "Munke", "given": "Anna", "initials": "A", "orcid": "0000-0002-5510-2245", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fd6d8030171420190aa65f3eb1ac4bd.json"}}, {"family": "Kimura", "given": "Kei", "initials": "K"}, {"family": "Tomaru", "given": "Yuji", "initials": "Y", "orcid": "0000-0002-8164-6991", "researcher": {"href": "https://publications.scilifelab.se/researcher/85835893ee10481aafee34223ece859e.json"}}, {"family": "Okamoto", "given": "Kenta", "initials": "K", "orcid": "0000-0002-4858-1196", "researcher": {"href": "https://publications.scilifelab.se/researcher/9302e76f16a04afdbb72f00c805bffa4.json"}}], "type": "journal article", "published": "2020-04-16", "journal": {"title": "J. Virol.", "issn": "1098-5514", "volume": "94", "issue": "9", "pages": null, "issn-l": "0022-538X"}, "abstract": "The order Picornavirales includes viruses that infect different kinds of eukaryotes and that share similar properties. The capsid proteins (CPs) of viruses in the order that infect unicellular organisms, such as algae, presumably possess certain characteristics that have changed little over the course of evolution, and thus these viruses may resemble the Picornavirales ancestor in some respects. Herein, we present the capsid structure of Chaetoceros tenuissimus RNA virus type II (CtenRNAV-II) determined using cryo-electron microscopy at a resolution of 3.1 \u00c5, the first alga virus belonging to the family Marnaviridae of the order Picornavirales A structural comparison to related invertebrate and vertebrate viruses revealed a unique surface loop of the major CP VP1 that had not been observed previously, and further, revealed that another VP1 loop obscures the so-called canyon, which is a host-receptor binding site for many of the mammalian Picornavirales viruses. VP2 has an N-terminal tail, which has previously been reported as a primordial feature of Picornavirales viruses. The above-mentioned and other critical structural features provide new insights on three long-standing theories about Picornavirales: (i) the canyon hypothesis, (ii) the primordial VP2 domain swap, and (iii) the hypothesis that alga Picornavirales viruses could share characteristics with the Picornavirales ancestor.IMPORTANCE Identifying the acquired structural traits in virus capsids is important for elucidating what functions are essential among viruses that infect different hosts. The Picornavirales viruses infect a broad spectrum of hosts, ranging from unicellular algae to insects and mammals and include many human pathogens. Those viruses that infect unicellular protists, such as algae, are likely to have undergone fewer structural changes during the course of evolution compared to those viruses that infect multicellular eukaryotes and thus still share some characteristics with the Picornavirales ancestor. This article describes the first atomic capsid structure of an alga Marnavirus, CtenRNAV-II. A comparison to capsid structures of the related invertebrate and vertebrate viruses identified a number of structural traits that have been functionally acquired or lost during the course of evolution. These observations provide new insights on past theories on the viability and evolution of Picornavirales viruses.", "doi": "10.1128/JVI.01855-19", "pmid": "32024776", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "JVI.01855-19"}, {"db": "pmc", "key": "PMC7163153"}], "notes": [], "created": "2020-05-07T09:32:06.291Z", "modified": "2023-12-04T10:14:40.858Z"}, {"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": "7670a9f949074cf49d2c78aad1523b49", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7670a9f949074cf49d2c78aad1523b49.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7670a9f949074cf49d2c78aad1523b49"}}, "title": "Human Adenovirus Infection Causes Cellular E3 Ubiquitin Ligase MKRN1 Degradation Involving the Viral Core Protein pVII.", "authors": [{"family": "Inturi", "given": "Raviteja", "initials": "R"}, {"family": "Mun", "given": "Kwangchol", "initials": "K"}, {"family": "Singethan", "given": "Katrin", "initials": "K"}, {"family": "Schreiner", "given": "Sabrina", "initials": "S"}, {"family": "Punga", "given": "Tanel", "initials": "T"}], "type": "journal article", "published": "2018-02-01", "journal": {"title": "J. Virol.", "issn": "1098-5514", "volume": "92", "issue": "3", "issn-l": "0022-538X"}, "abstract": "Human adenoviruses (HAdVs) are common human pathogens encoding a highly abundant histone-like core protein, VII, which is involved in nuclear delivery and protection of viral DNA as well as in sequestering immune danger signals in infected cells. The molecular details of how protein VII acts as a multifunctional protein have remained to a large extent enigmatic. Here we report the identification of several cellular proteins interacting with the precursor pVII protein. We show that the cellular E3 ubiquitin ligase MKRN1 is a novel precursor pVII-interacting protein in HAdV-C5-infected cells. Surprisingly, the endogenous MKRN1 protein underwent proteasomal degradation during the late phase of HAdV-C5 infection in various human cell lines. MKRN1 protein degradation occurred independently of the HAdV E1B55K and E4orf6 proteins. We provide experimental evidence that the precursor pVII protein binding enhances MKRN1 self-ubiquitination, whereas the processed mature VII protein is deficient in this function. Based on these data, we propose that the pVII protein binding promotes MKRN1 self-ubiquitination, followed by proteasomal degradation of the MKRN1 protein, in HAdV-C5-infected cells. In addition, we show that measles virus and vesicular stomatitis virus infections reduce the MKRN1 protein accumulation in the recipient cells. Taken together, our results expand the functional repertoire of the HAdV-C5 precursor pVII protein in lytic virus infection and highlight MKRN1 as a potential common target during different virus infections. IMPORTANCE Human adenoviruses (HAdVs) are common pathogens causing a wide range of diseases. To achieve pathogenicity, HAdVs have to counteract a variety of host cell antiviral defense systems, which would otherwise hamper virus replication. In this study, we show that the HAdV-C5 histone-like core protein pVII binds to and promotes self-ubiquitination of a cellular E3 ubiquitin ligase named MKRN1. This mutual interaction between the pVII and MKRN1 proteins may prime MKRN1 for proteasomal degradation, because the MKRN1 protein is efficiently degraded during the late phase of HAdV-C5 infection. Since MKRN1 protein accumulation is also reduced in measles virus- and vesicular stomatitis virus-infected cells, our results signify the general strategy of viruses to target MKRN1.", "doi": "10.1128/JVI.01154-17", "pmid": "29142133", "labels": {"PLA and Single Cell Proteomics": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "JVI.01154-17"}, {"db": "pmc", "key": "PMC5774890"}], "notes": [], "created": "2020-01-07T14:48:05.440Z", "modified": "2023-04-14T13:56:07.328Z"}], "created": "2020-01-07T14:48:05.446Z", "modified": "2020-11-27T13:14:01.405Z"}