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Delivery of genomes of nonenveloped DNA viruses into the cell nucleus
Bílková, Eva ; Forstová, Jitka (advisor) ; Hatáková, Ladislava (referee)
The majority of DNA viruses have to deliver their genome to the cell nucleus, which provi- des factors required for their replication and transcription. This work is focused on this proces of small nonenveloped DNA viruses. It describes delivery of the adenovirus, parvovirus, pa- pillomavirus and polyomavirus genomes into the cell nucleus. These viruses are endocyted by the cell and travel to the enveloped compartments. Viral particle undergoes changes afffected by surrounding environment and activity of cellular enzymes, which results in its escape from enveloped vesicle mediated by the viral proteins. Some viruses use direct interactions with cytos- keletal transport components for travelling to the cell nucleus. In most cases, viral DNA enters cell nucleus via nuclear pore complex, although the evidence of alternative mechanisms exists as well. This work focuses on early phases of the life cycle of the selected viruses and the nucleus targeting of their genomes. Understanding the mechanisms of viral DNA nuclear import may contribute to discovery of new anti-viral therapies.
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Rous sarcoma virus replication blocks in mammalian cells
Koslová, Anna ; Hejnar, Jiří (advisor) ; Ruml, Tomáš (referee) ; Weber, Jan (referee)
One of the important tasks of virology and immunology is to explore the species- and cell-barriers preventing virus horizontal transmission and reveal the ways how viruses overcome these barriers and "adapt" to different species. This work is based on a well- established retroviral model - avian Rous sarcoma virus (RSV) and studies virus replication blocks in mammalian cells at both pre- and post-integration level. Interaction of the viral envelope glycoprotein (Env) with a specific cellular receptor mediates virus entry into cells. Although mammalian orthologues of specific chicken receptors do not support RSV entry, it was observed that some RSV strains are able to enter mammalian cells. Several RSV-transformed rodent cells lines were described and analysis of provirus H20- RSV in one these cells lines (hamster H-20 tumor cell line) showed multiple mutations including two crucial amino acid substitutions in different regions of Env. Substitutions D32G and L378S confer virus transmission to hamster, human and also chicken cells lacking the appropriate receptor. Altered conformation of H20-RSV Env is similar to a receptor-primed (activated) state of Env. This observation indicates that virus can circumvent the need of original cell receptor because of spontaneous Env activation caused by single...
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Delivery of genomes of nonenveloped DNA viruses into the cell nucleus
Bílková, Eva ; Forstová, Jitka (advisor) ; Hatáková, Ladislava (referee)
The majority of DNA viruses have to deliver their genome to the cell nucleus, which provi- des factors required for their replication and transcription. This work is focused on this proces of small nonenveloped DNA viruses. It describes delivery of the adenovirus, parvovirus, pa- pillomavirus and polyomavirus genomes into the cell nucleus. These viruses are endocyted by the cell and travel to the enveloped compartments. Viral particle undergoes changes afffected by surrounding environment and activity of cellular enzymes, which results in its escape from enveloped vesicle mediated by the viral proteins. Some viruses use direct interactions with cytos- keletal transport components for travelling to the cell nucleus. In most cases, viral DNA enters cell nucleus via nuclear pore complex, although the evidence of alternative mechanisms exists as well. This work focuses on early phases of the life cycle of the selected viruses and the nucleus targeting of their genomes. Understanding the mechanisms of viral DNA nuclear import may contribute to discovery of new anti-viral therapies.
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