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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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Retroviral variants and their relationship to nonpermisive cells
Přikryl, David ; Hejnar, Jiří (advisor) ; Hirsch, Ivan (referee) ; Rumlová, Michaela (referee)
In my doctoral thesis, I focused on studying the envelope glycoprotein of ALV (Avian Leukosis Viruses), a group of retroviruses infecting Galliformes and inducing a variety of diseases. Eradication of these viruses in the farming industry is in progress and information about the virus spread, namely corresponding receptors, is needed to successfully accomplish this feat. Furthermore, many variants of retroviruses infect cells regardless of the absence of the corresponding receptor, and understanding of this phenomenon is also crucial. We analyzed a newly emerged subgroup of ALV, termed K for its sequence divergence from other subgroups, and determined its host range, interference, and receptor usage, to confirm whether this group deserves a new letter for its designation. We identified a receptor of ALV-K that proved to be Tva, the receptor also used by ALV-A. However, since the K subgroup differs from the A subgroup by its host range and inhibition by the soluble form of Tva, we expect the two subgroups use different epitopes of the Tva receptor. We also analyzed a variant of ALV-C exhibiting an extended host range as it successfully infected hamster cells. We found that the extended host range correlates with the ability of the envelope glycoprotein to acquire activated prefusion state...
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Virus translocation from cytoplasm to the cell nucleus
Išler, Lukáš ; Forstová, Jitka (advisor) ; Přikryl, David (referee)
Replication cycles of most DNA and some RNA viruses require translocation of these viruses into the host cell nucleus. In this step viruses must cross the nuclear membrane. In the cell cycle interphase, it can be exceeded only by passing through nuclear pores. Individual virus families have developed different strategies to efficiently translocate through the nuclear pore. In this paper, summarizing the knowledge of viral penetration through the nuclear pore, it is shown that in addition to the interaction with transport receptors, viral particles interact directly with some proteins of the nuclear pore complex, called nucleoporins (NUPs). Especially, one group of nucleoporins, so-called FG NUPs, interacts with viral particles. Their sequence contains naturally disordered domains rich in phenylalanine-glycine (FG) repeats which create selective barrier of the nuclear pore complex. These are mainly nucleoporins NUP153, NUP214 and NUP358. Interaction of viral particles with these nucleoporins allow them to cross this barrier and deliver their viral genome to the host cell nucleus. It is therefore an essential step in the early phase of the viral infection cycle. Keywords: cell nucleus, nuclear transport, nuclear pore complex, nucleoporins, virus nuclear entry, NUP153, NUP214, NUP358
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Polioviruses and poliovirus vaccines
Špika, Ondřej ; Drda Morávková, Alena (advisor) ; Přikryl, David (referee)
Polio is one of the diseases that humanity has been successfully fighting for more than half a century. The poliomyelitis virus that causes the disease can in some cases attack the nerve cells controlling the limbs and cause their paralysis. Especially dangerous are then the cases of infections of the respiratory neurons, which can lead to death without help. Mainly thanks to the scientists Salk and Sabin, two vaccines were created which, despite their disadvantages, successfully reduced the worldwide incidence of polio by 99%. However, there are still places where no vaccine is commonly available and where the virus is still endemic. The Salk vaccine, which was used first, uses an inactivated virus to prompt an immune response. However, its disadvantage is lower efficiency. Several years later, Sabin came with his live attenuated vaccine, unable to destroy human nerve cells. Sabin's vaccine conquered the world with simple oral administration and high efficacy. The disadvantage, which arises especially today, is the possibility of reverse mutation of the virus and the formation of pathogenic forms. This vaccine- derived virus can cause local outbreaks at low vaccination sites. Therefore, the use of the Sabine vaccine is being abandoned in favor of the Salk vaccine, possibly along with boosters. But...
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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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