Cellular and molecular basis of the host-pathogen relationships

Cellular and molecular basis of the host-pathogen relationships

Research is focused on characterization of mechanisms that participate in transmission of infectious agents, establishment/progress of infection in the host body, and pathogenesis. Virology research aims at the cell defense against infections caused by small DNA viruses (polyomavirus and hepatitis B virus) and HIV virus, particularly at the processes linked with restriction of virus infection by mechanisms of innate immunity; these mechanisms are operational during the early phase of virus‑cell interaction, i.e., during the transport of virus particles into the cell nucleus. Also, the mechanisms of cell defense evasion by viruses are analyzed. As for the most important results, epigenetic control via methylation of virus promotor has been disclosed in HIV replication. Bacteriology research is focused on proteins that modulate immune response; also secondary metabolites exhibiting diverse functions are studied, e.g., their influence on cell physiology including characterization of cytoskeleton, membraneous organelles, energy metabolism, production of oxygen radicals and regulation of cell cycle. In cooperation with the Institute of Microbiology ASCR, adenylate cyclase toxin produced by Bordetella pertussis and having immunomodulatory effects is intensively studied as a model protein. Among the most important results, influence of the toxin on endocytosis has been disclosed. Helminthology research deals with avian schistosomes that may attack humans as accidental hosts and cause cercarial dermatitis. Among the main research topics, the role of parasite peptidases and other enzymes in skin and tissue invasions, cellular and humoral immune response of the host, immune evasion of parasites, and pathogenesis linked with schistosome migration in the host tissues are in focus. Characterization of important parasite proteins is facilitated by recent genomic and transcriptomic projects. As for the most important results, morphological and biochemical characterization of penetration glands and cathepsins B1/B2 of schistosome larvae has been performed, and neuropathogenicity of Trichobilharzia regenti disclosed.

Selected outputs

  • Horák P., Mikeš L., Lichtenbergová L., Skála V., Soldánová M., Brant S. V. (2015): Avian schistosomes and outbreaks of cercarial dermatitis. Clinical Microbiology Reviews 28: 165-190.

  • Žíla V., Difato F., Klímová L., Huerfano S., Forstová J. (2014): Involvement of microtubular network and its motors in productive endocytic trafficking of mouse polyomavirus. PLOS ONE 9: e96922.

  • Fišer R., Mašín J., Bumba L., Pospíšilová E., Fayolle C., Basler M., Sadílková L., Adkins I., Kamanová J., Černý J., Konopásek I., Osička R., Leclerc C., Šebo P. (2012): Calcium influx rescues adenylate cyclase-hemolysin from rapid cell membrane removal and enables phagocyte permeabilization by toxin pores. PLOS Pathogens 8: e1002580.

  • Zona L., Lupberger J., Sidahmed-Adrar N., Thumann C., Harris H..J., Barnes A., Florentin J., Tawar R. G., Xiao F., Turek M., Durand S. C., Duong F. H., Heim M. H., Cosset F. L., Hirsch I., Samuel D., Brino L., Zeisel M. B., Le Naour F., McKeating J. A., Baumert T.F. (2013): HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex. Cell Host Microbe 13: 302-13.


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