<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Point Mutations in Nonstructural Coding Sequences of Rat \r\nH-1 Parvovirus and Consequences for Virus Fitness"^^ . "Some rodent parvoviruses including rat H-1PV virus are of particular importance for cancer\r\ntherapy because of their intrinsic oncotropism owing to strict dependence on DNA replication\r\nmachinery and other cellular factors that are provided by cells only when going through S phase\r\nof the cell cycle, a hallmark of transformed cells. Isolation of mutant viruses that replicate more\r\nefficiently in cancer cells has been used as a strategy to improve oncolytic properties of viruses.\r\nPreviously in our lab, a fully infectious H-1PV mutant containing a 114 nt in-frame deletion in NS\r\ncoding sequences (DelH-1PV) was analyzed by Weiss et al. This mutant exhibited key fitness\r\nfeatures including enhanced infectivity in vitro and stronger anti-tumor activity in vivo compared\r\nto wt virus. Significant improvements in both early and late steps of the virus cycle were\r\nobserved including a more efficient virus binding and uptake by host cells leading to earlier viral\r\nDNA replication, and earlier/faster nuclear export of infectious virions. In the current study, the\r\neffects of the above-mentioned deletion on virus fitness was further investigated by introducing\r\npoint mutations in this region. The mutations clustered in the NS1/2-coding DNA sequence\r\ncorresponding to the deletion sequence in DelH-1PV. Four mutants (H1-PM-I, H1-PM-II, H1-PM-III\r\nand H1-DM) were generated in which either NS2 (PM-II and PM-III) or NS1 and NS2(PM-I and\r\nDM) were modified and analyzed for their fitness phenotype. Our results show that the\r\nmutations PM-I, PM-II and DM improved some early steps of the infection cycle indicated by\r\nmore efficient cell uptake of the virus particles. Viral DNA replication was stimulated by these\r\nmutations leading to higher production of progeny virions and better spread of the virus. To\r\nanalyze the fitness effects of NS1 mutation (Y595H) independently of NS2, NS2-null derivatives\r\nwere created. Our data showed that the NS1Y595H mutation stimulates viral DNA replication and\r\nspread in the absence of NS2. In contrast, PM-III mutation in NS2 (L153M) compromised virus\r\nreplication and spread, indicated by a small plaque phenotype, lower yield and infectivity of the\r\nprogeny particles. However, cellular binding and uptake of the virus particles were not impaired\r\nby this mutation. A strong cis effect of PM-III mutation on capsid production was observed at a\r\npost-transcriptional level. Altogether our results suggest that PM-III mutation may interfere with\r\nefficient translation of downstream open reading frame (capsid ORF) and efficient splicing of\r\nVP1/VP2 pre-mRNA leading to decreased and imbalanced production of the capsid proteins and\r\nconsequently inefficient generation of pre-assembled capsids."^^ . "2017" . . . . . . . "Hamidreza"^^ . "Hashemi"^^ . "Hamidreza Hashemi"^^ . . . . . . "Point Mutations in Nonstructural Coding Sequences of Rat \r\nH-1 Parvovirus and Consequences for Virus Fitness (PDF)"^^ . . . "Thesis PDF.pdf"^^ . . . "Point Mutations in Nonstructural Coding Sequences of Rat \r\nH-1 Parvovirus and Consequences for Virus Fitness (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Point Mutations in Nonstructural Coding Sequences of Rat \r\nH-1 Parvovirus and Consequences for Virus Fitness (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Point Mutations in Nonstructural Coding Sequences of Rat \r\nH-1 Parvovirus and Consequences for Virus Fitness (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Point Mutations in Nonstructural Coding Sequences of Rat \r\nH-1 Parvovirus and Consequences for Virus Fitness (Other)"^^ . . . . . . "small.jpg"^^ . . . "Point Mutations in Nonstructural Coding Sequences of Rat \r\nH-1 Parvovirus and Consequences for Virus Fitness (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #22702 \n\nPoint Mutations in Nonstructural Coding Sequences of Rat \nH-1 Parvovirus and Consequences for Virus Fitness\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .