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  • 1. Alksnis, M.
    et al.
    Lindberg, A Michael
    Department of Medical Genetics, Uppsala University.
    Stålhanske, POK
    Hultberg, H.
    Pettersson, U.
    Use of synthetic oligodeoxyribonucleotides for type-specific identification of coxsackie B viruses1989In: Molecular and Cellular Probes, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 3, no 2, p. 103-108Article in journal (Refereed)
    Abstract [en]

    Synthetic oligodeoxyribonucleotides were used for type-specific identification of members of the coxsackie B virus group by nucleic acid hybridization. Two pairs of oligonucleotide chains were constructed based on nucleotide sequences in the VP1 regions of coxsackieviruses B3 and B4. Each labelled probe had a length of 24 nucleotides. The results showed that the oligonucleotide hybridized in a type-specific manner when assayed with extracts from cells infected with all different coxsackie B viruses. A method based on similar principles may thus be used for enterovirus typing.

  • 2. Andersson, P
    et al.
    Edman, Kjell
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Lindberg, A. Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Molecular analysis of the echovirus 18 prototype2002In: Virus research, Vol. 85, p. 71-83Article in journal (Refereed)
  • 3.
    Au, Gough G
    et al.
    The University of Newcastle.
    Lindberg, A Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Barry, Richard D
    The University of Newcastle.
    Shafren, Darren R
    The University of Newcastle.
    Oncolysis of vascular malignant human melanoma tumors by Coxsackievirus A21.2005In: International Journal of Oncology, ISSN 1019-6439, Vol. 26, no 6, p. 1471-6Article in journal (Refereed)
    Abstract [en]

    Cultured melanoma cell lines despite exhibiting similar in vitro morphology, display significant phenotypic and growth rate differences when propagated as in vivo xenografts. Previously we have shown that Coxsackievirus A21 (CVA21) lytically infects in vitro cultures of malignant melanoma cells and is efficient at reducing the tumor burden of mice bearing slow-growing SK-Mel-28 melanoma xenografts. The oncolytic activity of CVA21 against in vivo melanoma xenografts, which possess rapid growth rates and more extensive vascular structure than SK-Mel-28 xenografts warrants further investigation. In the present study we evaluated the oncolytic action of CVA21 against rapidly growing melanoma xenografts (ME4405) which exhibit a highly vascular phenotype. Flow cytometric analysis indicated that in vitro cultures of ME4405 cells expressed comparable levels of the CVA21 cellular receptors, ICAM-1 (intercellular adhesion molecules-1) and DAF (decay accelerating factor) to SK-Mel-28 cells. Despite similar levels of CVA21 receptor expression, SK-Mel-28 cells appear to be more susceptible to viral lysis than ME4405 cells, even though the kinetics of virus replication in both lines was comparable. Intratumoral, intraperitoneal or intravenous administration of CVA21 were equally effective in reducing the tumor volume of ME4405 xenografts in immunodeficient mice, and provides further evidence for the use of CVA21 as a novel oncolytic agent against varying phenotypes of malignant melanoma.

  • 4. Carlsson, Beatrice
    et al.
    Lindberg, A. Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Rodrigues-Díaz, Jesus
    Hedlund, Kjell-Olof
    Persson, Bengt
    Svensson, Lennart
    Quasispecies dynamics and molecular evolution of human norovirus capsid P region during chronic infection2009In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 90, no 2, p. 432-441Article in journal (Refereed)
    Abstract [en]

    In this novel study, we have for the first time identified evolutionarily conserved capsid residues in an individual chronically infected with norovirus (GGII.3). From 2000 to 2003, a total of 147 P1-1 and P2 capsid sequences were sequenced and investigated for evolutionarily conserved and functionally important residues by the evolutionary trace (ET) algorithm. The ET algorithm revealed more absolutely conserved residues (ACR) in the P1-1 domain (47/53, 88 %) as compared with the P2 domain (86/133, 64 %). The capsid P1-1 and P2 domains evolved in time-dependent manner, with a distinct break point observed between autumn/winter of year 2000 (isolates P1, P3 and P5) and spring to autumn of year 2001 (isolates P11, P13 and P15), which presumably coincided with a change of clinical symptoms. Furthermore, the ET analysis revealed a similar receptor-binding pattern as reported for Norwalk and VA387 strains, with the CS-4 and CS-5 patch (Norwalk strain) including residues 329 and 377 and residues 306 and 310, respectively, all being ACR in all partitions. Most interesting was that residues 343, 344, 345, 374, 390 and 391 of the proposed receptor A and B trisaccharide binding site (VA387 strain) within the P2 domain remained ACR in all partitions, presumably because there was no selective advantage to alter the histo blood group antigens (HBGA) receptor binding specificity. In conclusion, this study provides novel insights to the evolutionary process of norovirus during chronic infection.

  • 5.
    Ekström, Jens-Ola
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Andersson, P
    Edman, Kjell
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Widell, A
    Lindberg, A. Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Genetic and phylogenetic analyses of a coxsackievirus B (CVB) clinical isolate that can be neutralized by CVB4 and CVB5 monospecific antisera2003In: Infection, genetics and evolution, Vol. 2, p. 218-219Article in journal (Refereed)
  • 6.
    Ekström, Jens-Ola
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Tolf, Conny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Edman, Kjell
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Lindberg, A Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Physicochemical properties of the Ljungan virus virion in different environments: inactivated by heat but resistant th acidic pH, detergents, and non-physiological environments such as Virkon® containing soulutions2007In: Microbiology and immunology, ISSN 0385-5600, E-ISSN 1348-0421, Vol. 51, p. 841-850Article in journal (Refereed)
  • 7.
    Ekström, Jens-Ola
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Tolf, Conny
    Edman, Kjell
    Lindberg, Michael
    A novel mechanism for maturation of the VP1 protein of Ljungan virusManuscript (preprint) (Other (popular science, discussion, etc.))
  • 8.
    Ekström, Jens-Ola
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Tolf, Conny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Fahlgren, Camilla
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Johansson, Susanne
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Arbrandt, Gustav
    Apodemus, Stockholm.
    Niklasson, Bo
    Apodemus, Stockholm.
    Edman, Kjell
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Lindberg, A. Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Replication of Ljungan virus in cell culture: The genomic 5'-end, infectious cDNA clones and host cell response to viral infections2007In: Virus Research, ISSN 0168-1702, E-ISSN 1872-7492, Vol. 130, no December 2007, p. 129-139Article in journal (Refereed)
    Abstract [en]

    Ljungan virus (LV) is a picornavirus recently isolated from bank voles (Clethrionomys glareolus). The previously uncharacterised 5'-end sequence of the LV genome was determined. Infectious cDNA clones were constructed of the wild type LV prototype strain 87-012 and of the cytolytically replicating cell cultureadapted variant 87-012G. Virus generated from cDNA clones showed identical growth characteristics as uncloned virus stocks. Cell culture adapted LV, 87-012G, showed a clear cytopathic effect (CPE) at 3-4 days post-infection (p.i.). Virus titers, determined by plaque titration, increased however only within the first 18 h p.i. Replication of LV (+) strand RNA was determined by real-time PCR and corresponded in time with increasing titers. In contrast, the amounts of thereplication intermediate, the (-) strand, continued to increase until the cells showed CPE. This indicates separate controlling mechanisms for replication of LV (+) and (-) genome strands. Replication was also monitored by immunofluorescence (IF) staining. IF staining of both prototype 87-012 and the CPE causing 87-012G showed groups of 5-25 infected cells at 48 h p.i., suggesting a, for picornaviruses, not previously described direct cell-to-cell transmission.

  • 9. EL Hiar, Raida
    et al.
    Haddad, Samir
    Jaidane, Hela
    Hober, Didier
    Ben M'hadheb-Gharbi, Manel
    Gullberg, Maria
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Neji-Guediche, Mohamed
    Lindberg, A. Michael
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Gharbi, Jawhar
    Aouni, Mahjoub
    Enteroviral Central Nervous System Infections in Children of the Region of Monastir, Tunisia: Diagnosis, Laboratory Findings of Cerebrospinal Fluid and Clinical Manifestations2012In: Indian Journal of Virology, ISSN 0970-2822, Vol. 23, no 3, p. 294-302Article in journal (Refereed)
    Abstract [en]

    Human enteroviruses (HEV) are one of the major causes of central nervous system (CNS) infections in pediatrics. A prospective study was conducted to assess the epidemiological, clinical, and laboratory characteristics of enterovirus (EV) infections of the CNS in children under 15-years-old, suspected of having viral CNS infections and admitted to the Pediatric Department of Monastir University Hospital, Tunisia. Enteroviral RNA was detected by 5' NCR nested RT-PCR assay in 33 % (20 out of 60) of cerebrospinal fluid specimens, whereas only six samples (10 %) were EV positive in cell culture. EV-positive patients were clustered according to their clinical manifestations, predominantly diagnosed as aseptic meningitis (65 %) and meningoencephalitis (20 %). Fever, headache, vomiting, and neck stiffness were the most pronounced symptoms. Pleocytosis with the predominance of lymphocytes was observed in 60 % of EV positive specimens. Although patients suffering from EV infections were encountered throughout the year, most occurred during spring and summer months. Using VP1-2A nested RT-PCR and sequence analysis, three of the 20 positive HEV were identified as Echovirus (E)-9. This is the first report of a cluster of aseptic meningitis cases caused by E-9 in Monastir.

  • 10. Frisk, G
    et al.
    Lindberg, A Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Diderholm, H
    Persistence of Coxsackievirus B4 infection in rhabdomyosarcoma cells for 30 months1999In: Archives of Virology, Vol. 144, p. 2239-2245Article in journal (Refereed)
  • 11.
    Gullberg, Maria
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Tolf, Conny
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Jonsson, Nina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Mulders, Mick N
    Savolainen-Kopra, Carita
    Hovi, Tapani
    Van Ranst, Marc
    Lemey, Philippe
    Hafenstein, Susan
    Lindberg, A. Michael
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Characterization of a putative ancestor of coxsackievirus B5.2010In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 84, p. 9695-9708Article in journal (Refereed)
    Abstract [en]

    Like other RNA viruses, coxsackievirus B5 (CVB5) exists as circulating heterogeneous populations of genetic variants. In this study, we present the reconstruction and characterization of a probable ancestral virion of CVB5. Phylogenetic analyses based on capsid protein encoding regions (the VP1 gene of 41 clinical isolates and the entire P1 region of eight clinical isolates) of CVB5 revealed two major co-circulating lineages. Ancestral capsid sequences were inferred from sequences of these contemporary CVB5 isolates using maximum likelihood methods. By using Bayesian phylodynamic analysis, the inferred VP1 ancestral sequence was dated back to 1854 (1807-1898). In order to study the properties of the putative ancestral capsid, the entire ancestral P1 sequence was synthesized de novo and inserted into the replicative backbone of an infectious CVB5 cDNA clone. Characterization of the recombinant virus in cell culture showed that fully functional infectious virus particles were assembled and that these viruses displayed properties similar to those of modern isolates, in terms of receptor preferences, plaque phenotype, growth characteristics and cell tropism. This is the first report describing resurrection and characterization of a picornavirus with a putative ancestral capsid. Our approach, including phylogenetics-based reconstruction of viral predecessors, could serve as a starting point for experimental studies of viral evolution and might also provide an alternative strategy in the development of vaccines.

  • 12.
    Gullberg, Maria
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Tolf, Conny
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Jonsson, Nina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Polacek, Charlotta
    Precechtelova, Jana
    Badurova, Miriam
    Sojka, Martin
    Mohlin, Camilla
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Israelsson, Stina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Johansson, Kjell
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Bopegamage, Shubhada
    Hafenstein, Susan
    Lindberg, A. Michael
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    A single coxsackievirus B2 capsid residue controls cytolysis and apoptosis in rhabdomyosarcoma cells.2010In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 84, no 12, p. 5868-5879Article in journal (Refereed)
    Abstract [en]

    Coxsackievirus B2 (CVB2), one of six human pathogens of the group B coxsackieviruses within the enterovirus genus of Picornaviridae, causes a wide spectrum of human diseases ranging from mild upper respiratory illnesses to myocarditis and meningitis. The CVB2 prototype strain Ohio-1 (CVB2O) was originally isolated from a patient with summer grippe in the 1950s. Later on, CVB2O was adapted to cytolytic replication in rhabdomyosarcoma (RD) cells. Here, we present analyses of the correlation between the adaptive mutations of this RD variant and the cytolytic infection in RD cells. Using reverse genetics, we identified a single amino acid change within the exposed region of the VP1 protein (glutamine to lysine at position 164) as the determinant for the acquired cytolytic trait. Moreover, this cytolytic virus induced apoptosis, including caspase activation and DNA degradation, in RD cells. These findings contribute to our understanding of the host cell adaptation process of CVB2O and provide a valuable tool for further studies of virus-host interactions.

  • 13.
    Israelsson, Stina
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Ekström, Jens-Ola
    Department of Molecular Biology, Umeå University.
    Göransson, Anna
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Jonsson, Nina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Lindberg, A Michael
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Significance of an authentic 5´ genomic end for activation of viral replication using in vitro transcripts of echovirus 5 and its implication for the efficacy of oncolytic infectious nucleic acidManuscript (preprint) (Other academic)
  • 14.
    Israelsson, Stina
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Gullberg, Maria
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Jonsson, Nina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Roivainen, Merja
    Edman, Kjell
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Lindberg, A. Michael
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Studies of Echovirus 5 interactions with the cell surface: Heparan sulfate mediates attachment to the host cell.2010In: Virus Research, ISSN 0168-1702, E-ISSN 1872-7492, Vol. 151, no 2, p. 170-176Article in journal (Refereed)
    Abstract [en]

    Infections caused by Echovirus 5 (E5), an enterovirus of the Picornaviridae family, have been associated with fever, rashes and sporadic cases of aseptic meningitis. To elucidate the receptor usage of this virus, the significance of a previously proposed integrin binding arginine-glycine-aspartic acid (RGD) motif found in the VP3 capsid protein was investigated, as well as the capacity of E5 to interact with heparan sulfate on the cell surface. Using the prototype strain E5 Noyce (E5N), an E5N mutant where the aspartic acid of the RGD motif has been substituted to a glutamic acid and clinical E5 isolates, the RGD motif of VP3 was found to be non-essential and hence not involved in integrin receptor binding. However, E5N and clinical E5 isolates interact with heparan sulfate at the cell surface, as demonstrated by virus replication inhibition assays using heparin and heparinase III, and studies of E5 interactions at the cell surface measured by real-time PCR analysis. In conclusion, E5 utilizes heparan sulfate as a cellular receptor, but the RGD motif of VP3 is not essential for E5 infectivity.

  • 15.
    Israelsson, Stina
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Jonsson, Nina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Gullberg, Maria
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. Technical University of Denmark, Denmark.
    Lindberg, A. Michael
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Cytolytic replication of echoviruses in colon cancer cell lines2011In: Virology Journal, ISSN 1743-422X, E-ISSN 1743-422X, Vol. 8, article id e473Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Colorectal cancer is one of the most common cancers in the world, killing nearly 50% of patients afflicted. Though progress is being made within surgery and other complementary treatments, there is still need for new and more effective treatments. Oncolytic virotherapy, meaning that a cancer is cured by viral infection, is a promising field for finding new and improved treatments. We have investigated the oncolytic potential of several low-pathogenic echoviruses with rare clinical occurrence. Echoviruses are members of the enterovirus genus within the family Picornaviridae.

    METHODS: Six colon cancer cell lines (CaCo-2, HT29, LoVo, SW480, SW620 and T84) were infected by the human enterovirus B species echovirus 12, 15, 17, 26 and 29, and cytopathic effects as well as viral replication efficacy were investigated. Infectivity was also tested in spheroids grown from HT29 cells.

    RESULTS: Echovirus 12, 17, 26 and 29 replicated efficiently in almost all cell lines and were considered highly cytolytic. The infectivity of these four viruses was further evaluated in artificial tumors (spheroids), where it was found that echovirus 12, 17 and 26 easily infected the spheroids.

    CONCLUSIONS: We have found that echovirus 12, 17 and 26 have potential as oncolytic agents against colon cancer, by comparing the cytolytic capacity of five low-pathogenic echoviruses in six colon cancer cell lines and in artificial tumors.

  • 16.
    Israelsson, Stina
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Sävneby, Anna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Ekström, Jens-Ola
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science. Umeå universitet.
    Jonsson, Nina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Edman, Kjell
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Lindberg, A. Michael
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Improved replication efficiency of echovirus 5 after transfection of colon cancer cells using an authentic 5' RNA genome end methodology2014In: Investigational new drugs, ISSN 0167-6997, E-ISSN 1573-0646, Vol. 32, no 6, p. 1063-1070Article in journal (Refereed)
    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.

  • 17.
    Johannesson, Per
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Israelsson, Stina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Edman, Kjell
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Lindberg, A Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    A novel and rapid method to quantify cytolytic replication of picornaviruses in cell culture2005In: Journal of virological methods, Vol. 130, p. 117-123Article in journal (Refereed)
    Abstract [en]

    Determining viral titers is a key issue in a wide variety of studies regarding different aspects of virology. The standard methods used for determining picornavirus titers are endpoint titration assay and plaque assay, both time consuming and laborious. The method described uses the tetrazolium salt MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide) that is reduced to formazane by cellular dehydrogenase, genes shown to be down-regulated during picornavirus infection. The amount formazane produced correlates with the viral titers obtained and can easily be measured using an ELISA plate reader. The colorimetric method has been evaluated using virus types from different genera of the Picornaviridae family. The MTT method reduces the time spent on determining the viral titers and still maintains a reliable accuracy.

  • 18. Johansson, E S
    et al.
    Niklasson, B
    Tesh, R B
    R Shafren, Darren
    Travassos da Rosa, A P A
    Lindberg, A Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Molecular characterization of M1146, an American isolate of Ljungan virus (LV) reveals the presence of a new LV genotype2003In: Journal of general virology, Vol. 84, p. 837-844Article in journal (Refereed)
  • 19.
    Johansson, S
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Lindberg, Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Molecular characterization of Ljungan virus2001Conference paper (Refereed)
  • 20.
    Johansson, S
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Lindberg, Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Kinnunen, L
    University of Helsinki, Finland.
    Hyypiä, T
    University of Helsinki, Finland.
    Niklasson, B
    Uppsala University, Sweden.
    Ljungan virus: Genome analysis, genetic diversity and phylogenetic relationship to members of Picornaviridae1998Conference paper (Refereed)
  • 21.
    Johansson, S
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Niklasson, B
    Svensson, B
    Elfström, T
    Tesh, RB
    University of Texas, Galveston, USA.
    Lindberg, Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Molecular characterization of Ljungan virus strains - "new" members of the Picornaviridae2000In: EUROPIC 2000: XIth Meeting, Baia delle Zagare, Italy, 2000Conference paper (Refereed)
  • 22.
    Johansson, S
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nilsson, A
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Ohlson, S
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Lindberg, AM
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Towards studies of interactions between echovirus 7 and the receptor on human cells: sequence analysis of an infectious full-length clone1997In: 12th International Symposium on Affinity Interactions: Fundamentals and Applications of Biomolecular Recognition, Kalmar, Sweden, 1997Conference paper (Refereed)
  • 23.
    Johansson, Susanne
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Ekström, Jens-Ola
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Shafren, Darren
    Frisk, Gun
    Hyypiä, Timo
    Edman, Kjell
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Lindberg, Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Cell culture propagation and biochemical analysis of the Ljungan virus prototype strain2004In: Biochemical and Biophysical Research Communication, Vol. 317, no 4, p. 1023-1029Article in journal (Refereed)
    Abstract [en]

    Ljungan virus (LV) is proposed as a potentially important rodent harbored viral human pathogen. Little is known about the biophysical nature of the virus and despite being molecularly characterized, progress in epidemiological and basic biological studies of LV has been hampered by the lack of a robust and reliable cell culture propagation system. Here we report the first description of an efficient lytic multi-cycle cell culture propagation of the LV prototype strain (87-012). Biophysical analysis of gradient purified LV virions generated by this system identified mature infectious virions to possess a sedimentation coefficient of 160S and in agreement with previous molecular prediction, polyprotein analysis suggests that the native virion is composed of only three major structural proteins. The nucleotide composition of the complete genome of the LV cell culture adapted virus was determined and compared to that of the parental prototype LV. Numerous mutations were observed scattered throughout the viral genome and particularly in VP1. The development of this cell culture system for LV should open new avenues in the study of LV biology, structure, pathogenesis, and prevalence of natural infection in the wider community.

  • 24.
    Johansson, Susanne
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Niklasson, Bo
    Maizel, Jacob
    Gorbalenya, Alexander
    Lindberg, Michael
    Molecular analysis of three Ljungan virus isolates reveals a new, close-to-root lineage of the Picornaviridae with a cluster of two unrelated 2A proteins2002In: Journal of Virology, ISSN 0022-538X (print) 1098-5514 (online), Vol. 76, no 17, p. 8920-8930Article in journal (Refereed)
  • 25.
    Johansson, Susanne
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Polacek, Charlotta
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nilsson, Anne
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Ohlson, Sten
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Lindberg, A. Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Studies of weak-to-moderate virus-receptor interactions using uncloned viruses as well as an infectious cDNA clone of echovirus 7 strain Wallace1996Conference paper (Refereed)
  • 26.
    Jonsson, Nina
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Gullberg, Maria
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Israelsson, Stina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Lindberg, A. Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    A rapid and efficient method for studies of virus interaction at the host cell surface using enteroviruses and real-time PCR2009In: Virology Journal, ISSN 1743-422X, E-ISSN 1743-422X, Vol. 6, no Article ID: 217Article in journal (Refereed)
    Abstract [en]

    Background: Measuring virus attachment to host cells is of great importance when trying to identify novel receptors. The presence of a usable receptor is a major determinant of viral host range and cell tropism. Furthermore, identification of appropriate receptors is central for the understanding of viral pathogenesis and gives possibilities to develop antiviral drugs. Attachment is presently measured using radiolabeled and subsequently gradient purified viruses. Traditional methods are expensive and time-consuming and not all viruses are stable during a purification procedure; hence there is room for improvement. Real-time PCR (RT-PCR) has become the standard method to detect and quantify virus infections, including enteroviruses, in clinical samples. For instance, primers directed to the highly conserved 5' untranslated region (5'UTR) of the enterovirus genome enable detection of a wide spectrum of enteroviruses. Here, we evaluate the capacity of the RT-PCR technology to study enterovirus host cell interactions at the cell surface and compare this novel implementation with an established assay using radiolabeled viruses. Results: Both purified and crude viral extracts of CVB5 generated comparable results in attachment studies when analyzed with RT-PCR. In addition, receptor binding studies regarding viruses with coxsackie- nd adenovirus receptor (CAR) and/or decay accelerating factor (DAF) affinity, further demonstrated the possibility to use RT-PCR to measure virus attachment to host cells. Furthermore, the RT-PCR technology and crude viral extracts was used to study attachment with low multiplicity of infection (0.05 x 10(-4)TCID(50)/cell) and low cell numbers (250), which implies the range of potential implementations of the presented technique. Conclusion: We have implemented the well-established RT-PCR technique to measure viral attachment to host cells with high accuracy and reproducibility, at low cost and with less effort than traditional methods. Furthermore, replacing traditional methods with RT-PCR offers the opportunity to use crude virus containing extracts to investigate attachment, which could be considered as a step towards viral attachment studies in a more natural state.

  • 27.
    Jonsson, Nina
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Gullberg, Maria
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Lindberg, A. Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Real-time polymerase chain reaction as a rapid and efficient alternative to estimation of picornavirus titers by tissue culture infectious dose 50% or plaque forming units2009In: Microbiology and immunology, ISSN 0385-5600, E-ISSN 1348-0421, Vol. 53, no 3, p. 149-154Article in journal (Refereed)
    Abstract [en]

    Quantification of viral infectious units is traditionally measured by methods based on forming plaques in semisolid media (PFU) or endpoint dilution of a virus-containing solution (TCID(50)), methods that are laborious, time-consuming and take on average 3-7 days to carry out. Quantitative real-time PCR is an established method to quantify nucleic acids at high accuracy and reproducibility, routinely used for virus detection and identification. In the present study, a procedure was developed using a two-step real-time PCR and the SYBR Green detection method to study whether there are correlations between TCID(50)/ml, PFU/ml and Ct values generated by real-time PCR enabling rapid and efficient calculation of titer equivalents when working with viruses in the research laboratory. In addition, an external standard with known concentrations was included using in vitro transcribed viral RNA, thus allowing the calculation of the amount of RNA copies needed for various applications (i.e. per plaque or TCID(50)).The results show that there is a correlation between the three quantification methods covering a wide range of concentration of viruses. Furthermore, a general regression line between TCID(50) and Ct values was obtained for all viruses included in the study, which enabled recording titer equivalents using real-time PCR. Finally, by including an external standard, the amount of RNA genomes generating one TCID(50) or PFU for each enterovirus serotype included was determined.

  • 28.
    Jonsson, Nina
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Sävneby, Anna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Gullberg, Maria
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Evertsson, Kim
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Klingel, Karin
    University of Tübingen, Germany.
    Lindberg, A. Michael
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Efficient replication of recombinant Enterovirus B types, carrying different P1 genes in the coxsackievirus B5 replicative backbone2015In: Virus genes, ISSN 0920-8569, E-ISSN 1572-994X, Vol. 50, no 3, p. 351-357Article in journal (Refereed)
    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.

  • 29.
    Jonsson, Nina
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Wahlström, Kristin
    Svensson, Lennart
    Serrander, Lena
    Lindberg, A. Michael
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Aichi virus infection in elderly people in Sweden.2012In: Archives of Virology, ISSN 0304-8608, E-ISSN 1432-8798, Vol. 157, no 7, p. 1365-1369Article in journal (Refereed)
    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.

  • 30. Jääskeläinen, Anne J
    et al.
    Kolehmainen, Pekka
    Voutilainen, Liina
    Hauffe, Heidi C
    Kallio-Kokko, Hannimari
    Lappalainen, Maija
    Tolf, Conny
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Lindberg, A. Michael
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Henttonen, Heikki
    Vaheri, Antti
    Tauriainen, Sisko
    Vapalahti, Olli
    Evidence of ljungan virus specific antibodies in humans and rodents, Finland.2013In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 85, no 11, p. 2001-2008Article in journal (Refereed)
    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.

  • 31. Kim, MC
    et al.
    Kim, M-J
    Kwon, Y-K
    Lindberg, A. Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Joh, S-J
    Kwon, H-M
    Lee, Y-J
    Kwon, J-H
    Development of duck hepatitis A virus type 3 vaccine and its use to protect ducklings against infections2009In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 27, no 8, p. 6688-6694Article in journal (Refereed)
    Abstract [en]

    A variant type of duck hepatitis A virus (DHAV), DHAV-3 was recently discovered in South Korea and China. Sequence analyses verified that the variant is genetically or serologically different from the DHAV-1 and DHAV-2 types. Duck hepatitis had been reported in South Korea since 1985 and an attenuated DHAV-1 vaccine had efficiently prevented epidemics of DHAV-1 until 2002. Despite the DHAV-1 based vaccine in use the novel DHAV-3 circulating in South Korea remains to be a threat to duckling farming. To develop a live attenuated vaccine against DHAV-3, a representative isolate, AP-04203, was therefore attenuated by repeated passages in SPF chicken embryos 100 times. The 100th passaged virus, AP-04203P100, did not cause clinical sign and mortality in 1-day-old ducklings as well as reversion of virulence capacity. The ducklings vaccinated with AP-04203P100 virus (10(3.0) ELD(50)/0.2 ml) on 1-day-old age via the intramuscular injection were well protected from 2 days after challenge with pathogenic AP04203P1 virus via the intramuscular route. In addition, the vaccine candidate also exhibited complete protection against currently circulating pathogenic DHAV-3 isolates. In conclusion, we demonstrate that the live attenuated virus, AP-04203P100, is a promising vaccine candidate facilitating the prevention of duck hepatitis caused by DHAV-3 around East Asia including South Korea.

  • 32. Kim, M-C
    et al.
    Kwon, Y-K
    Joh, S-J
    Kim, S-J
    Tolf, Conny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Kim, J-H
    Sung, H-W
    Lindberg, A Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Kwon, J-H
    Recent Korean isolates of duck hepatitis virus reveal the presence of a novel geno- and serotype comparing to duck hepatitis virus type 1 strains2007In: Archives of Virology, ISSN 0304-8608, E-ISSN 1432-8798, Vol. 152, p. 2059-2072Article in journal (Refereed)
  • 33. Kim, M-C
    et al.
    Kwon, Y-K
    Joh, S-J
    Kwon, J-H
    Lindberg, A Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Differential diganosis between type-specific DHV-1 and recent Korean DHV-1 like isolates using a multiplex polymerase chain reaction2008In: Avian Pathology, ISSN 0307-9457, E-ISSN 1465-3338, Vol. 37, p. 171-177Article in journal (Refereed)
  • 34. Kim, M-C
    et al.
    Kwon, Y-K
    Joh, S-J
    Lindberg, A Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Kwon, J-H
    Kim, S-J
    Molecular analysis of duck hepatitis virus type 1 reveals a novel lineage close to the genus Parechovirus in the family Picornaviridae2006In: Journal of general virology, Vol. 87, p. 3307-3316Article in journal (Refereed)
  • 35. Knowles, N J
    et al.
    Hovi, T
    Hyypiä, T
    King, A M Q
    Lindberg, A. Michael
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Pallansch, M A
    Palmenberg, A C
    Simmonds, P
    Skern, T
    Stanway, G
    Yamashita, T
    Zell, R
    Family - Picornaviridae2012In: Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses / [ed] Andrew M.Q. King, Elliot Lefkowitz, Michael J. Adams and Eric B. Carstens, San Diego - London: Elsevier, 2012, p. 855-881Chapter in book (Refereed)
    Abstract [en]

    This chapter focuses on Picornaviridae family whose member genuses includeEnterovirus, Cardiovirus, Aphthovirus, Hepatovirus, and Parechovirus. The virions of this family consist of a capsid with no envelope and surrounds a core of ssRNA. Hydrated native particles are 30 nm in diameter, but vary from 22 to 30 nm in electron micrographs due to drying and flattening during preparation. The virions contain one molecule of positive sense, ssRNA, and possess a single long ORF. The UTRs at both termini contain regions of secondary structure, which are essential to genome function. In addition to the major CPs, 1A, 1B, 1C and 1D, and 3B (VPg), small amounts of 1AB (VP0) are commonly seen in lieu of one or more copies of 1A and 1B. Protein 1A is small in hepatoviruses, and 1AB is uncleaved in avihepatoviruses, kobuviruses, parechoviruses, and a number of unclassified picornaviruses. Some picornaviruses carry a sphingosine-like molecule in a cavity located inside 1D, and protein 1A generally has a molecule of myristic acid covalently attached to the amino terminal glycine. The virion RNA is infectious and serves as both the genome and the viral mRNA. Infection is generally cytolytic, but persistent infections are common with some species and reported with others. Poliovirus infected cells undergo extensive vacuolation as membranes are reorganized into viral replication complexes.

  • 36. Liljas, L.
    et al.
    Lindberg, A Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Pettersson, U.
    Modelling of the tertiary Structure of Coxsackievirus B3 from the Structure of Poliovirus and Rhinovirus1993In: Scandinavian journal of infectious diseases, Vol. Supplement 88, p. 15-24Article in journal (Refereed)
  • 37.
    Lindberg, A Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Generation of full-length single stranded cDNAs from various types of enteroviruses1994In: EUROPIC 94: VIIIth Meeting, Korpilampi, Finland, 1994Conference paper (Refereed)
  • 38.
    Lindberg, A Michael
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Molecular analysis of the group B coxsackievirus genomes2001In: Infectious disease reviews, Vol. 2, p. 232-233Article in journal (Refereed)
  • 39.
    Lindberg, A. Michael
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Andersson, A.
    Purification of full-length enterovirus cDNA by solid phase hybridization capture facilitates amplification of complete genomes1999In: Journal of virological methods, Vol. 77, p. 131-137Article in journal (Refereed)
  • 40.
    Lindberg, A. Michael
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Andersson, P
    Savolainen, C
    Mulders, M N
    Hovi, T
    Evolution of Human Enterovirus B genomes: incongruence between phylogenies of the VP1 and 3CD regions indicates frequent recombination within the species2003In: Journal of general virology, Vol. 84, p. 1223-1235Article in journal (Refereed)
  • 41.
    Lindberg, A Michael
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Crowell, R.L.
    Zell, R.
    Kandolf, R.
    Pettersson, U.
    Mapping of the RD phenotype of the Nancy strain of coxsackievirus B31992In: Virus research, Vol. 24, p. 187-196Article in journal (Refereed)
  • 42.
    Lindberg, A Michael
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Gräslund, T.
    Nilsson, J.
    Uhlén, M.
    Nygren, P.-Å.
    Production of a Thermostable DNA Polymerase by Site-Specific Cleavage of a Heat-Eluted Affinity Fusion Protein1997In: Protein expression and purification, Vol. 9, p. 125-132Article in journal (Refereed)
  • 43.
    Lindberg, A. Michael
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Johansson, Susanne
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Andersson, Anne
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Echovirus 5: infectious transcripts and complete nucleotide sequence from uncloned cDNA1999In: Virus Research, ISSN 0168-1702, Vol. 59, no 1, p. 75-87Article in journal (Refereed)
    Abstract [en]

    Echovirus 5 (EV5) may be isolated from various neurological and exanthematic diseases. To determine the relationship of EV5 to other enteroviruses and for studies of its interactions with the target cell, the complete nucleotide sequence of EV5 was determined. Three overlapping fragments, collectively representing the complete genome, were amplified with RT–PCR and sequenced. Analysis of the EV5 sequence revealed a typical enterovirus-like organization of the genome. To verify that the cDNA generated sequence was derived from infectious viruses, complete EV5 genomes were amplified in one amplicon by long distance PCR. Transfection of in vitro transcribed RNA from these amplicons into cell cultures resulted in replicating EV5. Comparison of the overall nucleotide and amino acid sequences demonstrates that EV5 can be regarded as a coxsackievirus B-like enterovirus. Variable sequences between EV5 and the well characterized coxsackievirus B3 (CVB3) are for the most part observed for amino acid residues that correspond to exposed sequences in the CVB3 capsid. This observation indicates that the reported EV5 strain recently diverged from group B coxsackieviruses.

  • 44.
    Lindberg, A. Michael
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nilsson, Anne
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Complete amplification of enterovirus genomes by long distance enterovirus-specific PCR (LDE-PCR) and the "Kalmar Collection" of infectious cDNA clones1996Conference paper (Refereed)
  • 45.
    Lindberg, A Michael
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Polacek, C
    Molecular analysis of the prototype coxsackievirus B5 genome2000In: Archives of Virology, Vol. 145, p. 205-221Article in journal (Refereed)
  • 46.
    Lindberg, A Michael
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Polacek, C
    Johansson, Susanne
    Amplification and cloning of complete enterovirus by long distance PCR1997In: Journal of virological methods, Vol. 65, p. 191-199Article in journal (Refereed)
  • 47.
    Lindberg, A. Michael
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Polacel, Charlotta
    University of Kalmar, School of Pure and Applied Natural Sciences.
    An efficient strategy for RT-PCR cloning of complete enterovirus sequences1995Conference paper (Refereed)
  • 48.
    Lindberg, A Michael
    et al.
    Department of Medical Genetics and Microbiology, Biomedical Center, University of Uppsala.
    Stålhanske, POK
    Pettersson, U.
    Genome of Coxsackievirus B31987In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 156, no 1, p. 50-63Article in journal (Refereed)
    Abstract [en]

    The entire nucleotide sequence of the coxsackievirus B3 strain Nancy (CB3) genome has been determined from cDNA. The genome is 7396 nucleotides long, and encodes a 2185 amino acid long polyprotein. It exhibits the same gene organization as other enterovirus genomes. A detailed comparison was carried out between the proteins encoded by the CB3 and poliovirus type 1 strain Mahoney (PVI) genomes. The genes encoding the VPg polypeptide and the viral polymerase are the most conserved regions. The structural polypeptides VP1, VP2, and VP3 are less well conserved although proline and tryptophan residues frequently are found in identical positions. The VP1 protein of CB3 shows a particularly limited homology in those regions which have been found to induce neutralizing antibodies against PV1. The 5′ noncoding region of CB3 is closely related to that of PV1, with regard to both length and sequence organization, whereas the 3′ noncoding region of CB3 exhibits some unique features. 

  • 49.
    Lindberg, Anders Michael
    et al.
    Uppsala University, Sweden.
    Alksnis, Marianne
    Uppsala University, Sweden.
    Stålhandske, Per
    Uppsala University, Sweden.
    Pettersson, Ulf
    Uppsala University, Sweden.
    Molecular biology of coxsackievirus1987Conference paper (Refereed)
  • 50.
    Lindberg, Anders Michael
    et al.
    Uppsala University, Sweden.
    Pettersson, Ulf
    Uppsala University, Sweden.
    Correlation between amino acid conservation in the P1 region of coxsackievirus type B and a model of the three dimensional structure of coxsackievirus B31989Conference paper (Refereed)
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