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BETA
Lindberg, A. MichaelORCID iD iconorcid.org/0000-0003-3841-4826
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Publications (10 of 96) Show all publications
Zell, R., Delwart, E., Gorbalenya, A. E., Hovi, T., King, A. M., Knowles, N. J., . . . Yamashita, T. (2017). ICTV Virus Taxonomy Profile: Picornaviridae. Journal of General Virology, 98(10), 2421-2422
Open this publication in new window or tab >>ICTV Virus Taxonomy Profile: Picornaviridae
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2017 (English)In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 98, no 10, p. 2421-2422Article in journal (Refereed) Published
Abstract [en]

The family Picornaviridae comprises small non-enveloped viruses with RNA genomes of 6.7 to 10.1 kb, and contains > 30 genera and > 75 species. Most of the known picornaviruses infect mammals and birds, but some have also been detected in reptiles, amphibians and fish. Many picornaviruses are important human and veterinary pathogens and may cause diseases of the central nervous system, heart, liver, skin, gastrointestinal tract or upper respiratory tract. Most picornaviruses are transmitted by the faecal-oral or respiratory routes. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Picornaviridae, which is available at www. ictv. global/report/picornaviridae.

Keywords
Picornaviridae, ICTV, taxonomy, poliovirus, foot-and-mouth disease virus, rhinovirus, enterovirus
National Category
Microbiology
Research subject
Biomedical Sciences, Virology
Identifiers
urn:nbn:se:lnu:diva-69753 (URN)10.1099/jgv.0.000911 (DOI)000417310000004 ()28884666 (PubMedID)
Available from: 2018-01-12 Created: 2018-01-12 Last updated: 2018-01-12Bibliographically approved
Mullapudi, E., Novacek, J., Palkova, L., Kulich, P., Lindberg, A. M., van Kuppeveld, F. J. M. & Plevka, P. (2016). Structure and Genome Release Mechanism of the Human Cardiovirus Saffold Virus 3. Journal of Virology, 90(17), 7628-7639
Open this publication in new window or tab >>Structure and Genome Release Mechanism of the Human Cardiovirus Saffold Virus 3
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2016 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 90, no 17, p. 7628-7639Article in journal (Refereed) Published
Abstract [en]

In order to initiate an infection, viruses need to deliver their genomes into cells. This involves uncoating the genome and transporting it to the cytoplasm. The process of genome delivery is not well understood for nonenveloped viruses. We address this gap in our current knowledge by studying the uncoating of the nonenveloped human cardiovirus Saffold virus 3 (SAFV-3) of the family Picornaviridae. SAFVs cause diseases ranging from gastrointestinal disorders to meningitis. We present a structure of a native SAFV-3 virion determined to 2.5 angstrom by X-ray crystallography and an 11-angstrom-resolution cryo-electron microscopy reconstruction of an "altered" particle that is primed for genome release. The altered particles are expanded relative to the native virus and contain pores in the capsid that might serve as channels for the release of VP4 subunits, N termini of VP1, and the RNA genome. Unlike in the related enteroviruses, pores in SAFV-3 are located roughly between the icosahedral 3- and 5-fold axes at an interface formed by two VP1 and one VP3 subunit. Furthermore, in native conditions many cardioviruses contain a disulfide bond formed by cysteines that are separated by just one residue. The disulfide bond is located in a surface loop of VP3. We determined the structure of the SAFV-3 virion in which the disulfide bonds are reduced. Disruption of the bond had minimal effect on the structure of the loop, but it increased the stability and decreased the infectivity of the virus. Therefore, compounds specifically disrupting or binding to the disulfide bond might limit SAFV infection. IMPORTANCE A capsid assembled from viral proteins protects the virus genome during transmission from one cell to another. However, when a virus enters a cell the virus genome has to be released from the capsid in order to initiate infection. This process is not well understood for nonenveloped viruses. We address this gap in our current knowledge by studying the genome release of Human Saffold virus 3. Saffold viruses cause diseases ranging from gastrointestinal disorders to meningitis. We show that before the genome is released, the Saffold virus 3 particle expands, and holes form in the previously compact capsid. These holes serve as channels for the release of the genome and small capsid proteins VP4 that in related enteroviruses facilitate subsequent transport of the virus genome into the cell cytoplasm.

National Category
Microbiology
Research subject
Biomedical Sciences, Virology
Identifiers
urn:nbn:se:lnu:diva-57044 (URN)10.1128/JVI.00746-16 (DOI)000382306800004 ()27279624 (PubMedID)2-s2.0-84983560201 (Scopus ID)
Available from: 2016-10-05 Created: 2016-10-04 Last updated: 2017-11-30Bibliographically approved
Sabin, C., Fuzik, T., Skubnik, K., Palkova, L., Lindberg, A. M. & Plevka, P. (2016). Structure of Aichi Virus 1 and Its Empty Particle: Clues to Kobuvirus Genome Release Mechanism. Journal of Virology, 90(23), 10800-10810
Open this publication in new window or tab >>Structure of Aichi Virus 1 and Its Empty Particle: Clues to Kobuvirus Genome Release Mechanism
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2016 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 90, no 23, p. 10800-10810Article in journal (Refereed) Published
Abstract [en]

Aichi virus 1 (AiV-1) is a human pathogen from the Kobuvirus genus of the Picornaviridae family. Worldwide, 80 to 95% of adults have antibodies against the virus. AiV-1 infections are associated with nausea, gastroenteritis, and fever. Unlike most picornaviruses, kobuvirus capsids are composed of only three types of subunits: VP0, VP1, and VP3. We present here the structure of the AiV-1 virion determined to a resolution of 2.1 angstrom using X-ray crystallography. The surface loop puff of VP0 and knob of VP3 in AiV-1 are shorter than those in other picornaviruses. Instead, the 42-residue BC loop of VP0 forms the most prominent surface feature of the AiV-1 virion. We determined the structure of AiV-1 empty particle to a resolution of 4.2 angstrom using cryo-electron microscopy. The empty capsids are expanded relative to the native virus. The N-terminal arms of capsid proteins VP0, which mediate contacts between the pentamers of capsid protein protomers in the native AiV-1 virion, are disordered in the empty capsid. Nevertheless, the empty particles are stable, at least in vitro, and do not contain pores that might serve as channels for genome release. Therefore, extensive and probably reversible local reorganization of AiV-1 capsid is required for its genome release. IMPORTANCE Aichi virus 1 (AiV-1) is a human pathogen that can cause diarrhea, abdominal pain, nausea, vomiting, and fever. AiV-1 is identified in environmental screening studies with higher frequency and greater abundance than other human enteric viruses. Accordingly, 80 to 95% of adults worldwide have suffered from AiV-1 infections. We determined the structure of the AiV-1 virion. Based on the structure, we show that antiviral compounds that were developed against related enteroviruses are unlikely to be effective against AiV-1. The surface of the AiV-1 virion has a unique topology distinct from other related viruses from the Picornaviridae family. We also determined that AiV-1 capsids form compact shells even after genome release. Therefore, AiV-1 genome release requires large localized and probably reversible reorganization of the capsid.

National Category
Microbiology
Research subject
Biomedical Sciences, Virology
Identifiers
urn:nbn:se:lnu:diva-59721 (URN)10.1128/JVI.01601-16 (DOI)000389904500030 ()2-s2.0-85000963069 (Scopus ID)
Available from: 2017-01-10 Created: 2017-01-10 Last updated: 2017-11-29Bibliographically approved
Sävneby, A., Luthman, J., Nordenskjold, F., Andersson, B. & Lindberg, A. M. (2016). The Transcriptome of Rhabdomyosarcoma Cells Infected with Cytolytic and Non-Cytolytic Variants of Coxsackievirus B2 Ohio-1. PLoS ONE, 11(10), Article ID e0164548.
Open this publication in new window or tab >>The Transcriptome of Rhabdomyosarcoma Cells Infected with Cytolytic and Non-Cytolytic Variants of Coxsackievirus B2 Ohio-1
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 10, article id e0164548Article in journal (Refereed) Published
Abstract [en]

The transcriptomes of cells infected with lytic and non-lytic variants of coxsackievirus B2 Ohio-1 (CVB2O) were analyzed using next generation sequencing. This approach was selected with the purpose of elucidating the effects of lytic and non-lytic viruses on host cell transcription. Total RNA was extracted from infected cells and sequenced. The resulting reads were subsequently mapped against the human and CVB2O genomes. The amount of intracellular RNA was measured, indicating lower proportions of human RNA in the cells infected with the lytic virus compared to the non-lytic virus after 48 hours. This may be explained by reduced activity of the cellular transcription/translation machinery in lytic enteroviral replication due to activities of the enteroviral proteases 2A and/or 3C. Furthermore, differential expression in the cells infected with the two virus variants was identified and a number of transcripts were singled out as possible answers to the question of how the viruses interact with the host cells, resulting in lytic or non-lytic infections.

National Category
Microbiology
Research subject
Biomedical Sciences, Virology
Identifiers
urn:nbn:se:lnu:diva-58203 (URN)10.1371/journal.pone.0164548 (DOI)000386204000039 ()2-s2.0-84992035054 (Scopus ID)
Available from: 2016-11-18 Created: 2016-11-18 Last updated: 2018-11-01Bibliographically approved
Jonsson, N., Sävneby, A., Gullberg, M., Evertsson, K., Klingel, K. & Lindberg, A. M. (2015). Efficient replication of recombinant Enterovirus B types, carrying different P1 genes in the coxsackievirus B5 replicative backbone. Virus genes, 50(3), 351-357
Open this publication in new window or tab >>Efficient replication of recombinant Enterovirus B types, carrying different P1 genes in the coxsackievirus B5 replicative backbone
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2015 (English)In: Virus genes, ISSN 0920-8569, E-ISSN 1572-994X, Vol. 50, no 3, p. 351-357Article in journal (Refereed) Published
Abstract [en]

Recombination is an important feature in theevolution of the Enterovirus genus. Phylogenetic studies ofenteroviruses have revealed that the capsid genomic region(P1) is type specific, while the parts of the genome codingfor the non-structural proteins (P2–P3) are species specific.Hence, the genome may be regarded as consisting of twomodules that evolve independently. In this study, it wasinvestigated whether the non-structural coding part of thegenome in one type could support replication of a virus witha P1 region from another type of the same species. A cas-sette vector (pCas) containing a full-length cDNA copy ofcoxsackievirus B5 (CVB5) was used as a replicative back-bone. The P1 region of pCas was replaced with the corre-sponding part from coxsackievirus B3Nancy(CVB3N),coxsackievirus B6Schmitt(CVB6S), and echovirus 7Wal-lace(E7W), all members of theEnterovirus Bspecies. Thereplication efficiency after transfection with clone-derivedin vitro transcribed RNA was studied and compared withthat of pCas. All the recombinant viruses replicated with similar efficiencies and showed threshold cycle (Ct) values,tissue culture infectivity dose 50 %, and plaque-forming unittiters comparable to viruses generated from the pCas con-struct. In addition to this, a clone without the P1 region wasalso constructed, and Western Blot and immunofluorescencestaining analysis showed that the viral genome could betranslated and replicated despite the lack of the structuralprotein-coding region. To conclude, the replicative back-bone of the CVB5 cassette vector supports replication ofintraspecies constructs with P1 regions derived from othermembers of theEnterovirus Bspecies. In addition to this,the replicative backbone can be both translated and repli-cated without the presence of a P1 region.

National Category
Biochemistry and Molecular Biology
Research subject
Biomedical Sciences, Virology
Identifiers
urn:nbn:se:lnu:diva-41538 (URN)10.1007/s11262-015-1177-x (DOI)000355233000001 ()25663145 (PubMedID)2-s2.0-84929956418 (Scopus ID)
Available from: 2015-04-01 Created: 2015-04-01 Last updated: 2017-12-04Bibliographically approved
Zhu, L., Wang, X., Ren, J., Porta, C., Wenham, H., Ekström, J.-O., . . . Stuart, D. I. (2015). Structure of Ljungan virus provides insight into genome packaging of this picornavirus. Nature Communications, 6, Article ID 8316.
Open this publication in new window or tab >>Structure of Ljungan virus provides insight into genome packaging of this picornavirus
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2015 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, article id 8316Article in journal (Refereed) Published
Abstract [en]

Picornaviruses are responsible for a range of human and animal diseases, but how their RNA genome is packaged remains poorly understood. A particularly poorly studied group within this family are those that lack the internal coat protein, VP4. Here we report the atomic structure of one such virus, Ljungan virus, the type member of the genus Parechovirus B, which has been linked to diabetes and myocarditis in humans. The 3.78-angstrom resolution cryo-electron microscopy structure shows remarkable features, including an extended VP1 C terminus, forming a major protuberance on the outer surface of the virus, and a basic motif at the N terminus of VP3, binding to which orders some 12% of the viral genome. This apparently charge-driven RNA attachment suggests that this branch of the picornaviruses uses a different mechanism of genome encapsidation, perhaps explored early in the evolution of picornaviruses.

Keywords
Biological sciences, Biophysics, Virology
National Category
Microbiology
Research subject
Biomedical Sciences, Virology
Identifiers
urn:nbn:se:lnu:diva-47715 (URN)10.1038/ncomms9316 (DOI)000364920600001 ()26446437 (PubMedID)2-s2.0-84943631507 (Scopus ID)
Available from: 2015-12-04 Created: 2015-12-04 Last updated: 2017-12-01Bibliographically approved
Israelsson, S., Sävneby, A., Ekström, J.-O., Jonsson, N., Edman, K. & Lindberg, A. M. (2014). Improved replication efficiency of echovirus 5 after transfection of colon cancer cells using an authentic 5' RNA genome end methodology. Investigational new drugs, 32(6), 1063-1070
Open this publication in new window or tab >>Improved replication efficiency of echovirus 5 after transfection of colon cancer cells using an authentic 5' RNA genome end methodology
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2014 (English)In: Investigational new drugs, ISSN 0167-6997, E-ISSN 1573-0646, Vol. 32, no 6, p. 1063-1070Article in journal (Refereed) Published
Abstract [en]

Oncolytic virotherapy is a promising novel form of cancer treatment, but the therapeutic efficiency needs improvement. A potential strategy to enhance the therapeutic effect of oncolytic viruses is to use infectious nucleic acid as therapeutic agent to initiate an oncolytic infection, without administrating infectious viral particles. Here we demonstrate improved viral replication activation efficiency when transfecting cells with 5’ end authentic in vitro transcribed enterovirus RNA as compared to genomic RNA with additional non-genomic 5’ nucleotides generated by conventional cloning methods. We used echovirus 5 (E5) as an oncolytoc model virus due to its ability to replicate in and completely destroy five out of six colon cancer cell lines and kill artificial colon cancer tumors (HT29 spheroids), as shown here. An E5 infectious cDNA clone including a hammerhead ribozyme sequence was used to generate in vitro transcripts with native 5’ genome ends. In HT29 cells, activation of virus replication is approximately 20-fold more efficient for virus genome transcripts with native 5’ genome ends compared to E5 transcripts generated from a standard cDNA clone. This replication advantage remains when viral progeny release starts by cellular lysis 22 h post transfection. Hence, a native 5’ genomic end improves infection activation efficacy of infectious nucleic acid, potentially enhancing its therapeutic effect when used for cancer treatment. The clone design with a hammerhead ribozyme is likely to be applicable to a variety of oncolytic positive sense RNA viruses for the purpose of improving the efficacy of oncolytic virotherapy.

Keywords
Picornavirus, RNA virus, Enterovirus, Oncolytic virotherapy, Hammerhead ribozyme, Infectious nucleic acid
National Category
Biochemistry and Molecular Biology
Research subject
Biomedical Sciences, Virology
Identifiers
urn:nbn:se:lnu:diva-41541 (URN)10.1007/s10637-014-0136-z (DOI)000345142300002 ()2-s2.0-84938677294 (Scopus ID)
Available from: 2015-04-01 Created: 2015-04-01 Last updated: 2017-12-04Bibliographically approved
Jääskeläinen, A. J., Kolehmainen, P., Voutilainen, L., Hauffe, H. C., Kallio-Kokko, H., Lappalainen, M., . . . Vapalahti, O. (2013). Evidence of ljungan virus specific antibodies in humans and rodents, Finland.. Journal of Medical Virology, 85(11), 2001-2008
Open this publication in new window or tab >>Evidence of ljungan virus specific antibodies in humans and rodents, Finland.
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2013 (English)In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 85, no 11, p. 2001-2008Article in journal (Refereed) Published
Abstract [en]

Ljungan virus (LV, genus Parechovirus, family Picornaviridae) is considered currently to be a rodent-borne virus. Despite suggested human disease associations, its zoonotic potential remains unclear. To date, LV antibody prevalence in both humans and rodents has not been studied. In this study, two different LV immunofluorescence assays (LV IFAs) were developed with LV genotypes 1 (LV strain 87-012G) and 2 (LV strain 145SLG), and cross-neutralization and -reaction studies were carried out with LV strain 145SLG. Finally, a panel of 37 Finnish sera was screened for anti-LV antibodies using two different LV IFAs (LV 145SLG and LV 87-012G) and a neutralization (NT) assay (LV 145SLG), and 50 samples from Myodes glareolus by LV IFA (LV 145SLG). The LV seroprevalence study showed 38% and 18% positivity in humans and M. glareolus, respectively. LV IFAs and NT assays were compared, and the results were in good agreement. The data are the first evidence of humans and rodents coming into contact with LV in Finland. Additional studies are required in order to acquire a better understanding of the prevalence, epidemiological patterns and possible disease association of LV infections.

National Category
Microbiology Infectious Medicine
Research subject
Biomedical Sciences, Virology
Identifiers
urn:nbn:se:lnu:diva-30618 (URN)10.1002/jmv.23681 (DOI)000329198500020 ()23852812 (PubMedID)2-s2.0-84883055074 (Scopus ID)
Available from: 2013-11-20 Created: 2013-11-20 Last updated: 2017-12-06Bibliographically approved
Persson, M., Gullberg, M., Tolf, C., Lindberg, A. M., Månsson, A. & Kocer, A. (2013). Transportation of Nanoscale Cargoes by Myosin Propelled Actin Filaments. PLoS ONE, 8(2), Article ID e55931.
Open this publication in new window or tab >>Transportation of Nanoscale Cargoes by Myosin Propelled Actin Filaments
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 2, article id e55931Article in journal (Refereed) Published
Abstract [en]

Myosin II propelled actin filaments move ten times faster than kinesin driven microtubules and are thus attractive candidates as cargo-transporting shuttles in motor driven lab-on-a-chip devices. In addition, actomyosin-based transportation of nanoparticles is useful in various fundamental studies. However, it is poorly understood how actomyosin function is affected by different number of nanoscale cargoes, by cargo size, and by the mode of cargo-attachment to the actin filament. This is studied here using biotin/fluorophores, streptavidin, streptavidin-coated quantum dots, and liposomes as model cargoes attached to monomers along the actin filaments ("side-attached") or to the trailing filament end via the plus end capping protein CapZ. Long-distance transportation (> 100 mu m) could be seen for all cargoes independently of attachment mode but the fraction of motile filaments decreased with increasing number of side-attached cargoes, a reduction that occurred within a range of 10-50 streptavidin molecules, 1-10 quantum dots or with just 1 liposome. However, as observed by monitoring these motile filaments with the attached cargo, the velocity was little affected. This also applied for end-attached cargoes where the attachment was mediated by CapZ. The results with side-attached cargoes argue against certain models for chemomechanical energy transduction in actomyosin and give important insights of relevance for effective exploitation of actomyosin-based cargo-transportation in molecular diagnostics and other nanotechnological applications. The attachment of quantum dots via CapZ, without appreciable modulation of actomyosin function, is useful in fundamental studies as exemplified here by tracking with nanometer accuracy.

National Category
Biochemistry and Molecular Biology
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-24860 (URN)10.1371/journal.pone.0055931 (DOI)000315186000012 ()2-s2.0-84874337312 (Scopus ID)
Available from: 2013-03-22 Created: 2013-03-22 Last updated: 2017-12-06Bibliographically approved
Jonsson, N., Wahlström, K., Svensson, L., Serrander, L. & Lindberg, A. M. (2012). Aichi virus infection in elderly people in Sweden.. Archives of Virology, 157(7), 1365-1369
Open this publication in new window or tab >>Aichi virus infection in elderly people in Sweden.
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2012 (English)In: Archives of Virology, ISSN 0304-8608, E-ISSN 1432-8798, Vol. 157, no 7, p. 1365-1369Article in journal (Refereed) Published
Abstract [en]

Aichi virus (AiV), genus Kobuvirus, family Picornaviridae, is associated with gastroenteritis in humans. Previous studies have shown high seroprevalence but low incidence (0.9-4.1%) in clinical samples. We report here the first detection of AiV in Sweden. Two hundred twenty-one specimens from hospitalized patients with diarrhea, who were negative for other enteric viruses, were included in the study. AiV were detected in three specimens, all from elderly patients. Phylogenetic analysis revealed that the three Swedish isolates belonged to genotype A and were genetically closest to European and Asian strains of AiV.

National Category
Microbiology
Research subject
Biomedical Sciences, Virology
Identifiers
urn:nbn:se:lnu:diva-22833 (URN)10.1007/s00705-012-1296-9 (DOI)22466255 (PubMedID)2-s2.0-84863086885 (Scopus ID)
Available from: 2012-12-14 Created: 2012-12-12 Last updated: 2017-12-06Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0003-3841-4826

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