Prehľad oddelení / Departments summary

Zelník V, Lapuníková B, Kúdelová M. Marek΄s disease: rapid progress in research with unclear biological implementations. Acta Virol. 2013;57(2):265-70.

Over the past few years, we have been focused on 4 major research topics:

• ECOLOGY OF ARBOVIRUSES, molecular determinants of TBEV virus transmission and adaptation to vectors, tick saliva factors involved in tick-borne pathogen transmission

• HANTAVIRUSES, molecular epidemiology, evolution, and pathogenesis

• EUROPEAN VIRUS ARCHIVE, establishment and maintenance of the European virus archive (supported by the FP EU project), biological and molecular characterization of the deposited viruses, collection and identification of new viruses

• BIOACTIVE MOLECULES IN TICK SALIVA, tick evasion mechanisms to circumvent the immune control of the hosts

Arbovirus (Arthropode-borne virus) and rodent-borne virus infections represent serious health problem for both human and animal populations. Research on arboviruses, particularly on the tick-borne encephalitis virus (TBEV) and on hantaviruses belong to the profiling topics of the institute and have been present since its founding. Our current research interests benefit from and extend the previous work. In the field of arboviruses, our focus lies on further elucidation of the non-viraemic transmission of tick-borne pathogens between co-feeding ticks in the TBEV-tick-mouse model developed in our group. Our interests in the field of hantavirus molecular epidemiology, led to the identification of several new hantaviruses, not only in the Central Europe but also in Africa and Russia. Experiences and achievements in these two scientific fields allowed us to become a member of the European Virus Archive, an EU supported infrastructure focused on the collection, maintenance, characterization, and distribution of viruses for research and development. Our research focused on bioactive molecules in tick saliva includes the identification and characterization of cytokine- and growth factor-binding proteins.

ecology-bsl3

Klempa B, Radosa L, Kruger DH. The broad spectrum of hantaviruses and their hosts in Central Europe. Acta Virol. 2013;57(2):130-7.

Over the past few years, we have been focused on 4 major research topics:

• CARBONIC ANHYDRASE IX (CA IX), a functional component of tumor hypoxia, its regulation and role in cancer, and its diagnostic and therapeutic application

• LYMPHOCYTIC CHORIOMENINGITIS VIRUS (LCMV), persistent infection, mechanisms of spread and reactivation, and its medical importance

• S100P CALCIUM-BINDING PROTEIN, its transcriptional regulation and interacting partners

• ENDOSIALIN (TEM1), a marker of tumor vasculature, its regulation and biological function

Our research interests represent a continuation of previous work that included cloning, characterization of molecular parameters, elucidation of several regulatory pathways and biological roles of the CA IX protein in cancer, as well as molecular characterization of the novel MX strain of LCMV persistently infecting human cells. We also generated antibodies for detection and targeting of CA IX as well as the nucleoprotein of MX LCMV, and contributed to the development of the translational aspects on both topics. Our recent investigations include hypoxia as an important physiological factor that considerably affects both tumor development and virus infection, in order to clarify its relationship with regulation and the biological roles in pathology.

medicine migration

Sedlakova O, Svastova E, Takacova M, Kopacek J, Pastorek J, Pastorekova S. Carbonic anhydrase IX, a hypoxia-induced catalytic component of the pH regulating machinery in tumors. Front Physiol. 2014 Jan 8;4:400.

In the past few years, we have been focused on 5 major research topics:

• HERPES SIMPLEX VIRUS, namely pathogenesis of attenuated strains of HSV1, immune response and cytokine production following immunization with recombinant protein/s and DNA vaccines containing either selected domain/s or full-length glycoprotein D (gD) in the experimental model of Balb/c mice; the role of UL27.5 counterpart of HSV-1 gB in the virus life cycl;, preparation and characterization of recombinant HSV-1 viruses; mechanisms of the antiviral action of some antiviral drugs against acute and latent infections caused by HSV-1 strains in vitro and in vivo

• HUMAN HERPESVIRUSES (HSV-1, HSV-2, HCMV, EBV, VZV), novel diagnostics of mixed herpetic infection

• MURINE GAMMAHERPESVIRUS (MuHV-4), as a model for investigating human gammaherpesvirus infections (EBV, KSHV), persistent infections, mechanisms of reactivation from latency, interaction between M3 and K3 during acute infection, genetic diversity and virulence-determining factors of MuHV-4 strains in vitro and in vivo, the role of ticks in MuHV-4 circulation in nature, the properties and therapeutic usefulness of immunomodulatory MuHV M3 protein

• INFLUENZA A, B, AND C VIRUSES, function of extracellular and intracellular domains of M2 protein, characterization of ion channel activity of BM2 and CM2, antiviral activity of siRNAs directed against different genes of influenza A virus, antiviral effects of interferons lambda

• PREVALENCE OF AVIAN INFLUENZA VIRUSES AND OTHER PATHOGENS IN BIRDS, surveillance of avian influenza viruses and other pathogens in migratory birds, waterfowl and terrestrial birds in Slovakia

Herpesviruses remain for the most part of lifecycle latent but under stimuli they may at any time be recalled into activity and provoke a visible herpetic infection. Chronic infection with some of them causes lymphoproliferative diseases and cancer. Understanding the adaptive strategies that allowed all herpesviruses to be transmitted efficiently and persist so successfully in the human population is the permanent aim of herpes-virologists. Our research represents the continuation of previous studies on interaction of Herpes simplex virus with host, effectiveness of vaccination and treatment with antiviral drugs against HSV-1 infection, and reactivation of herpesviruses from latency, on diagnostics of human herpesviruses and on Murine gammaherpesvirus serving as a model for the study of the human gammaherpesvirus pathogenesis. Our current efforts are aimed at better understanding the reactivation mechanisms of herpesviruses from latency and finding proteins supporting the virus escape from the host immune response, as tools for immunomodulating therapies.

Influenza virus is a common respiratory pathogen that represents constant threat for humans. Our research interests include comparison of the activities of BM2 protein of influenza B virus and CM2 protein of influenza C virus with M2 protein of influenza A virus, study of the roles of N- and C-domain of M2 protein in activity and replication of influenza A virus, surveillance of zoonotic pathogens transmissible to humans in Slovakia, and the development of siRNAs against different genes of influenza virus and evaluation of their inhibition potential towards virus replication in vitro and in vivo, as well as exploration of the biological activities of type I IFN-λs against replication of influenza A virus.

pathogenesis-model

Lopušná K, Režuchová I, Betáková T, Skovranová L, Tomašková J, Lukáčiková L, Kabát P. Interferons lambda, new cytokines with antiviral activity. Acta Virol. 2013;57(2):171-9.

Influenza viruses have been the subject of basic and applied research at the Institute of Virology since its establishment in 1953. Recently, at the Department of Orthomyxoviruses, the research has been focused on the study of immunology and pathogenesis of influenza A viruses (IAV), putting emphasis on the role of antigenically conserved proteins. The development of influenza diagnostics utilizing our monoclonal antibodies is primary target of applied research. Immunological studies are predominantly focused on antibody response against the HA2gp – conserved part of the major influenza antigen haemagglutinin. Research on the pathogenesis of the influenza infection has extended our knowledge concerning the spread of virus in various organs in mice with respect to different pathogenicity of particular virus strains. The determination of molecular changes connected with the adaptation of various avian influenza viruses in mice or other mammalian host is ongoing. Studies of the role of newly discovered influenza protein PB1-F2 in pathogenesis of infection are also being carried out. The effect of particular amino acid substitutions in PB1-F2 is studied using the reverse-genetics approach.

orthomyxoviruses-pathway

Košík I, Práznovská M, Košíková M, Bobišová Z, Hollý J, Varečková E, Kostolanský F, Russ G. The ubiquitination of the influenza A virus PB1-F2 protein is crucial for its biological function. PLoS One. 2015 Apr 13;10(4):e0118477.

In recent years, we have been focused on the following major research topics:

• PLUM POX VIRUS, the most important pathogen of stone fruits, its molecular variability, and virus-host interactions at the molecular level

• INFECTIOUS CLONE AND VIRAL VECTOR based on the PPV genome

• DETECTION AND CHARACTERIZATION OF ECONOMICALLY IMPORTANT VIRUSES of cucurbits, cereals, and grapevines

Epidemiologically and economically important plant viruses, particularly the RNA viruses of the stone fruits, grapevine, cucurbits, and cereals, were studied based on four basic aspects: (1) molecular characterization of these viruses in order to obtain the original data on their genetic diversity and evolutionary relationships (for example these results led to the discovery and/or the first characterization of four of eight presently recognized virus strains of the Plum pox virus and provided new insight into the evolution of this potyvirus); (2) development and optimization of molecular tools for a sensitive and specific detection of pathogens; (3) analysis of biological and molecular factors influencing the spread, epidemiology, and adaptation of plant viruses, including diagnostic evaluation of their capability to break the resistance of host plants; (4) functional genomics to study genetic determinants involved in the pathogenesis. Moreover, the epidemiological studies of the cucurbit, cereal and grapevine viruses were carried out for the first time on the territory of Slovakia. The results of these studies have thus direct implications for agricultural practice with the potential to improve the phytosanitary measures aimed at controlling plant viruses.

plant-regeneration

García JA, Glasa M, Cambra M, Candresse T. Plum pox virus and sharka: a model potyvirus and a major disease. Mol Plant Pathol. 2014 Apr;15(3):226-41.

In the recent years, we have been focused on 4 major research topics:

• ECOLOGY OF RICKETTSIAL AGENTS, monitoring of rickettsial agents in natural loci, isolation of new species and their characterization in relation to their vectors and reservoirs (ticks, lice, mites, wild and domestic animals) including the elucidation of mechanisms of their spread and circulation in nature

• HOST-PATHOGEN INTERACTIONS, detection and molecular characterization of pathogens (Rickettsiae, Coxiella burnetii and other rickettsia-like organisms) by the methods of molecular biology, serology, and immunology in order to improve diagnosis of these re-emerging rickettsial infections

• PROTEOMICS, systematic identification of protein biomarkers, surface-associated, virulence-related, and immunoreactive proteins with the aim of fishing for protein candidates involved in virulence, pathogenesis, and immunity

• GLYCOMICS, structure/function relationship studies of lipopolysaccharides that appear to be one of the major factors of virulence of intracellular bacteria and play an important role in host-pathogen interactions. Search for biomarkers and specific glycoimmunogens to improve detection and prophylaxis of Q fever and other infections

Our research interests represent a continuation of the preceding work that has been focused on medical, biological, molecular, and epizootological aspects of ontogenesis of the intracellular pathogens that certainly contribute to a better understanding of the pathogenesis, diagnosis, and prophylaxis of the re-emerging diseases they cause. Recent molecular and biochemical/immunological advances, along with an improved instrumentation, have provided unique insight into the host-parasite interrelationship and revealed previously unknown virulence strategies of the microorganisms under study. Noticeable progress has also been achieved in a better understanding of the role of 2 major outer membrane components – a lipopolysaccharide (LPS) and proteins in the life and pathobiology of these bacteria. Detailed glycomic studies have brought indispensable structural and functional information on LPS and its role in pathogenesis and immunity. In addition, recent proteomic studies have brought a deeper insight into the pathogen`s physiology, virulence and development, and offered new possibilities in investigations of inter/intra-species variation.

rickettsiology-coxiella

Bohácsová M, Filipčík P, Opattová A, Valáriková J, Quevedo Diaz M, Škultéty L, Novák M, Sekeyová Z. Survival of rat cerebrocortical neurons after rickettsial infection. Microbes Infect. 2015 Nov-Dec;17(11-12):845-9.