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Study of the assembly and budding of mouse mammary tumor virus MMTV
Hoboth, Peter ; Zábranský, Aleš (advisor) ; Forstová, Jitka (referee)
Mouse mammary tumor virus (MMTV) is a prototypical member of the Betaretrovirus genus characterized by the ability to preassemble viral particles in the cytoplasm of the host cells. Intracellularly preassembled particles are subsequently transported to the plasma membrane being enveloped by a lipid bilayer and released from the cell in the process referred to as budding. Retrovirus particle assembly is driven by the Gag polyprotein precursor, which is cleaved in the maturation process by virus-encoded protease to liberate multiple structural proteins. The matrix (MA), capsid (CA) and nucleocapsid (NC) protein domains that are common to all retroviruses and in the case of MMTV, also the noncanonical domains, pp21, p3, p8 and "n", located between MA and CA domain are present. The role of these specific domains remains undefined. The retroviral budding is stimulated by short peptide motifs, so-called late (L) domains, located within Gag sequence. These L domains mediate interactions with cellular proteins normally involved in the biogenesis of the multivesicular bodies and protein sorting. Three types of the L domains have been identified to date, with the consensus of the amino acid sequences (i) P(T/S)AP, (ii) YP(x)nL (where x represents any amino acid and n≤3) and (iii) PPxY. Disruption of the L domain...
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Effect of HBV protein HBx on activation of MEK1/2 signaling and inhibition of type I IFN in hepatoma cell line Huh7
Berehovska, Olena ; Hirsch, Ivan (advisor) ; Zábranský, Aleš (referee)
Hepatitis B virus (HBV) infection is one of the major causes of chronic and cancerous liver disease. Elimination of HBV from chronically infected patients by recombinant interferon α (IFNα) monotherapy shows that the mechanisms of the innate immunity play an important role in suppressing viral infection. However, the mechanisms of recognition of the HBV genome and its escape from the mechanisms of natural immunity are still little known. One of the principal factors enabling the virus to escape from cellular restriction mechanisms is the HBx viral protein. HBx is a 154 amino acid pleiotropic multifunctional protein affecting transcription, signal transduction, cell cycle, protein degradation, apoptosis, and chromosomal stability in the host cell. Previous results from our laboratory have shown that activation of the MEK1/2-ERK signaling pathway in plasmacytoid dendritic cells leads to inhibition of IFNα production. The aim of my work was to determine whether HBx activates the MEK1/2-ERK pathway and thus inhibits IFN type I production also in hepatocytes. For this purpose, I monitored HBx production in the Huh7 hepatoma cell line by transfecting the bicistronic plasmid pHBx- IRES-EGFP and Western blotting. Using the same method, I monitored activation of the MEK1/2-ERK signaling pathway by ERK...
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Study of the assembly and budding of mouse mammary tumor virus MMTV
Hoboth, Peter ; Zábranský, Aleš (advisor) ; Forstová, Jitka (referee)
Mouse mammary tumor virus (MMTV) is a prototypical member of the Betaretrovirus genus characterized by the ability to preassemble viral particles in the cytoplasm of the host cells. Intracellularly preassembled particles are subsequently transported to the plasma membrane being enveloped by a lipid bilayer and released from the cell in the process referred to as budding. Retrovirus particle assembly is driven by the Gag polyprotein precursor, which is cleaved in the maturation process by virus-encoded protease to liberate multiple structural proteins. The matrix (MA), capsid (CA) and nucleocapsid (NC) protein domains that are common to all retroviruses and in the case of MMTV, also the noncanonical domains, pp21, p3, p8 and "n", located between MA and CA domain are present. The role of these specific domains remains undefined. The retroviral budding is stimulated by short peptide motifs, so-called late (L) domains, located within Gag sequence. These L domains mediate interactions with cellular proteins normally involved in the biogenesis of the multivesicular bodies and protein sorting. Three types of the L domains have been identified to date, with the consensus of the amino acid sequences (i) P(T/S)AP, (ii) YP(x)nL (where x represents any amino acid and n≤3) and (iii) PPxY. Disruption of the L domain...
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