| 1. |
- Au, Gough G, et al.
(författare)
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Oncolysis of vascular malignant human melanoma tumors by Coxsackievirus A21.
- 2005
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 26:6, s. 1471-6
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
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| 3. |
- Johansson, Susanne, et al.
(författare)
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Cell culture propagation and biochemical analysis of the Ljungan virus prototype strain
- 2004
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Ingår i: Biochemical and Biophysical Research Communication. - : Elsevier BV. - 0006-291X. ; 317:4, s. 1023-1029
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Newcombe, Nicole G, et al.
(författare)
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Cellular receptor interactions of C-cluster human group A coxsackieviruses.
- 2003
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Ingår i: Journal of General Virology. - London : Society for General Microbiology. - 0022-1317 .- 1465-2099. ; 84:Pt 11, s. 3041-3050
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Tidskriftsartikel (refereegranskat)abstract
- The cellular receptor complex of coxsackievirus A21 (CVA21), a C-cluster human enterovirus, is formed by the subtle interaction of individual cellular receptors, decay accelerating factor (DAF) and intercellular adhesion molecule-1 (ICAM-1). In this receptor complex, DAF functions in the membrane sequestration of the virus, while the role of ICAM-1 is as the functional cellular internalization receptor. However, despite the elucidation of the CVA21-cell receptor interactions, there have been few definite investigations into cellular receptor usage of other coxsackie A viruses (CVAs) belonging to the C-cluster. In the present study, radiolabelled virus-binding assays demonstrated that CVA13, -15, -18 and -20, a subset of the human enterovirus C-cluster, bind directly to surface-expressed ICAM-1, but not to surface-expressed DAF. Furthermore, lytic infection of ICAM-1-expressing rhabdomyosarcoma (RD) cells by this C-cluster subset of viruses was inhibited by specific ICAM-1 monoclonal antibody blockade, except for that of CVA20. Despite possessing ICAM-1-binding capabilities, CVA20 employed an as yet unidentified internalization receptor for cell entry and subsequent productive lytic infection of ICAM-1-negative RD cells. In a further example of C-cluster cellular receptor heterogeneity, CVA13 exhibited significant binding to the surface of CHO cells expressing neither DAF nor ICAM-1. Despite a common receptor usage of ICAM-1 by this subset of C-cluster CVAs, the amino acid residues postulated to represent the ICAM-1-receptor footprint were not conserved.
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| 7. |
- Newcombe, Nicole G, et al.
(författare)
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Enterovirus capsid interactions with decay-accelerating factor mediate lytic cell infection
- 2004
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Ingår i: Journal of Virology. - London : Society for General Microbiology. - 0022-538X .- 1098-5514. ; 78:3, s. 1431-9
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Tidskriftsartikel (refereegranskat)abstract
- The cellular receptor usage of numerous human enteroviruses can differ significantly between low-cell-culture-passaged clinical isolates and highly laboratory-passaged prototype strains. The prototype strain of coxsackievirus A21 (CVA21) displays a dual-receptor specificity as determined with a receptor complex consisting of decay-accelerating factor (DAF) and intercellular adhesion molecule 1 (ICAM-1). In this study, the cellular receptor interactions of low-cell-passage CVA21 clinical isolates with respect to their interactions with cell surface-expressed DAF and ICAM-1 were compared to those of the CVA21 prototype (Kuykendall) strain. Dual-receptor usage of DAF and ICAM-1 by CVA21 clinical isolates was confirmed by cell transfection and radiolabeled binding assays. The cellular attachment of clinical and prototype CVA21 strains to cells that coexpressed DAF and ICAM-1 was not additive compared to the viral binding to cells expressing one or other receptor. In fact, the binding data suggest there is an inhibition of CVA21 cellular attachment in environments where high-level coexpression of both DAF and ICAM-1 occurs. Antibody cross-linking of DAF rendered cells susceptible to lytic infection by the CVA21 clinical isolates. In a novel finding, three clinical isolates could, to various degrees, infect and lyse DAF-expressing cells in the absence of DAF-antibody cross-linking and ICAM-1 expression. Sequence analysis of the P1 region of clinical and prototype virus genomes identified a number of coding changes that may contribute to the observed enhanced DAF usage phenotype of the clinical CVA21 isolates. None of the amino acid changes was located in the previously postulated ICAM-1 footprint, a receptor-binding environment that was conserved on the capsid surface of all CVA21 clinical isolates. Taken together, the data suggest that community-circulating strains of CVA21 can infect target cells expressing either ICAM-1 or DAF alone and that such interactions extend tissue tropism and impact directly on viral pathogenesis.
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