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Proteins mimicking epitopes of broadly neutralizing HIV-1 antibodies
Zosinčuková, Tereza ; Malý, Petr (advisor) ; Osička, Radim (referee)
HIV-1 is a dangerous retrovirus which represents one of the world's leading health problems. HIV-1 infection is incurable and without proper treatment by antiretroviral therapy it leads to death within several years. Despite intensive research, no HIV vaccine is currently available. This thesis presents a new and unique approach which has not been used for vaccine development yet. The promising strategy is based on small binding proteins that can elicit broadly neutralizing HIV-1 antibodies by mimicking their epitopes. The aim of this project was to select and characterize small binding proteins that can successfully mimic the surface of viral envelope glycoproteins that is recognized by the broadly neutralizing HIV-1 antibodies PGT121 and PGT126. Proteins were selected from a highly complex combinatorial protein library derived from a new type of scaffold called Myomedin. Firstly, the extent of the protein library was narrowed down using the ribosome display. Then the direct sandwich ELISA screening was applied to select scaffold variants that interact with the target antibodies. In total over 200 variants were tested and several promising candidates were found. These Myomedin variants were purified, biochemically and biophysically characterised and the best ones were used to immunize mice....
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Properties and functions of agnoprotein of polyomaviruses
Zosinčuková, Tereza ; Forstová, Jitka (advisor) ; Vinšová, Barbora (referee)
Polyomaviridae family includes small DNA viruses with simple structure and a small genome encoding only a few proteins. These proteins include large T and small T antigens, as well as 2 to 3 structural proteins known as VP1, VP2 and VP3. In addition, some members of the Polyomaviridae family encode in their genome a small non-structural protein called agnoprotein. Among human polyomaviruses, agnoprotein is present in BK polyomavirus and JC polyomavirus. These viruses are the causative agents of some serious diseases in immunocompromised humans and therefore, they are the subject of intensive research. Simian vacuolating virus 40 is another example of a virus which encodes the agnoprotein. Agnoprotein is capable to manipulate its host cell, disrupt vesicle transport and is also crucial for viral replication and transcription. It appears to play an important role in the morphogenesis of virions and/or in their release from the cell. This paper comprehensively summarizes the latest insights into the properties and functions of the agnoprotein BK polyomavirus, JC polyomavirus and SV40 virus, focusing on the production of this protein during infection, its structure, posttranslational modifications, cell localization, interaction partners and the overall importance of this enigmatic protein for the...
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