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Interaction of retroviral env glycoproteins with receptors and virus entry into the cell
Přikryl, David ; Pečenka, Vladimír (advisor) ; Horníková, Lenka (referee)
Humankind has adjusted many animals, plants and bacteria to serve their needs. Now the time has come to exploit also viruses. The most significant applications for them seem to lie in the sphere of human health. Particularly the family of retroviruses represent a perfekt vectors for gene delivery to cure genetic diseases or to destroy undesirable, e.g. cancer cells. In order to efficiently use these vehicles, a series of problems must be overcome and some segments of retroviral life cycle must be more deeply explored. This work describes some of them along with possible ways to solve them. The first described area is nonspecific adsorption of virions on the cell surface, the second is securing effective interaction between envelope glycoproteins and receptors highly specific for the targeted cell type and finally driven fusion of membranes. Key words: retrovirus, adsorption, env, receptor, phusion
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Identification of genes responsible for tumor induction with avian retroviruses subgroup J
Gašpareková, Mária ; Pečenka, Vladimír (advisor) ; Španielová, Hana (referee)
Retroviruses are viruses which are able to integrate to genome of host cell. Nonrandom integration of provirus near or inside some cellular genes may result in their deregulation, activation or silencing. This can later lead to cell transformation and tumor formation. This thesis discusses identification of viral integration sites (VIS) and common integration sites (CIS) in tumors originating from different organs (mostly kidneys, lungs and liver) with using mostly avian retroviruses subgroup J, specifically first natural isolate HPRS-103 and laboratory made virus MAV-J, which was made by replacing gene envB by envJ. Infection was made in ovo using chicken breeds Brown Leghorn and White Leghorn and tumors were isolated from 8 to 28 weeks after infection. For molecular analyses was used inverse PCR method and sequencing. From 74 molecularly analyzed tumors there was detected 373 VIS and 6 CIS with statistical significance over 2.10-2 . Gene with the highest number of hits was FRK (14 times), then TERT (5 times), CTDSPL (5 times), EGFR/ERBB1 (3 times), MYB (3 times) and MYC (3 times). Except 6 CIS there were other genes found, which had smaller statistical significance. Keywords: retrovirus, insertional mutagenesis, subgroup J, oncogenesis, oncogenes, MAV-J, HPRS-103, proviral integration sites, tumors
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Interaction of retroviral env glycoproteins with receptors and virus entry into the cell
Přikryl, David ; Pečenka, Vladimír (advisor) ; Horníková, Lenka (referee)
Humankind has adjusted many animals, plants and bacteria to serve their needs. Now the time has come to exploit also viruses. The most significant applications for them seem to lie in the sphere of human health. Particularly the family of retroviruses represent a perfekt vectors for gene delivery to cure genetic diseases or to destroy undesirable, e.g. cancer cells. In order to efficiently use these vehicles, a series of problems must be overcome and some segments of retroviral life cycle must be more deeply explored. This work describes some of them along with possible ways to solve them. The first described area is nonspecific adsorption of virions on the cell surface, the second is securing effective interaction between envelope glycoproteins and receptors highly specific for the targeted cell type and finally driven fusion of membranes. Key words: retrovirus, adsorption, env, receptor, phusion
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Study of replication and pathogenesis of retroviruses with extended host range.
Přikryl, David ; Pečenka, Vladimír (advisor) ; Horníková, Lenka (referee)
Coevolution of pathogens and their hosts leads to selection of series mutations. From the hosts point of view we can these accumulated mutations characterize as restriction factors preventing effecive replication of target pathogen, for example retrovirus. These factors acts on level of virion entry into cell, its intergation, expression and maturation. On the other hand, from the viruses point of view these mutations manifests the ability to overcome restriction factors mentioned earlier. One of the mechanizms is for example shift in receptor specifity, which allows to virus infect hosts in case, where original specific receptor is for some reason unavailable. This thesis focus on effect point mutation L154S in envelope glycoprotein of virus MAV-B and its influence in replication and pathogenesis in vitro and in vivo. For this purpose we infected and analyzed chicken breed of white and brown leghorns and different cell cultures. Results of infection of chickens displayed increased incidence of osteopetrosis, disease displaying the hyperthrophy of bone matter. In consistence with literature, we shown polyclonal origin of this neoplasia. With series of experiments we discovered abnormal behavior of envelope glycoprotein coded by virus causing this disease. Abnormality lies in termal lability and...
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