Characterization and targetint virus-host interaction

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00567308" target="_blank" >RIV/61388963:_____/22:00567308 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.ccsss.cz/index.php/ccsss/issue/view/37/67" target="_blank" >http://www.ccsss.cz/index.php/ccsss/issue/view/37/67</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Characterization and targetint virus-host interaction

Popis výsledku v původním jazyce

Chronic hepatitis is a life-long liver disease caused by infection of Hepatitis B virus (HBV). Despite the existence of preventive vaccine, more than 250 million people worldwide suffer from chronic hepatitis. Current treatment, involving nucleos(t)ide analogs or pegylated interferon-alpha, has many adverse side effects and does not provide functional cure because it is unable to clear HBV from infected cells. HBV is a small enveloped virus that encodes only few viral genes. The replication of the virus entirely relies on host environment and the viral proteins evolved to perform multiple functions. The HBc protein is a perfect example of virus-host interaction that is critical for the establishment and maintenance of persistent infections. While HBc is the main structural component of the viral nucleocapsid, additional regulatory roles of HBc in the viral life cycle and pathogenesis have been described (Fig. 1).The research of Jan Weber’s group is focused on identification of novel core-host interactions and characterization of cellular pathways that play role in HBV-associated pathogenesis1. Another important aspect of the research is to elucidate how various posttranslational modifications, e.g. serine phosphorylation, arginine methylation, ubiquitination or sumoylation, affect the HBc protein stability, intracellular trafficking or interaction with other proteins2,3. Using affinity purification/mass spectrometry assay we identified a pool of potential HBc interacting proteins. Among them, we selected three groups of promising candidates with potential effect on HBV replication: i) host factors with E3 ubiquitin ligase or kinase activities that may regulate HBc posttranslational modifications, e.g. serine phosphorylation or ubiquitin-like modifications, ii) proteins involved in epigenetic modifications, transcriptional control and nucleosome assembly that may affect viral cccDNA formation, activity and maintenance, iii) host chaperone proteins with potential role in viral nucleocapsid formation, pgRNA encapsidation and reverse transcription. The results generated by proposed comprehensive analysis of HBc –host interaction pathways would bring novel knowledge into HBV field and eventually lead to development of new promising anti-HBV therapies.In addition, our group is interested in characterization and targeting coronavirus attachment and entry. The emergence of third coronavirus causing severe acute respiratory syndrome in less than two decades transformed emerging coronaviruses in a new public health concern. Since SARS-CoV-2 detection in Wuhan in late 2019, the virus spread in almost every country, totaling so far 5 million deaths. It became obvious that we need a broad-spectrum intervention, that would halt this and future coronavirus pandemic. One of the best measures is to block virus before it establishes new infection in the cells, thus inhibition of viral attachment and entry are self-evident choices. Many viruses use abundant adhesion molecules such as heparan sulfate proteoglycan at surface for initial attachment to the cells4. We plan to characterize and target this interaction with sulfated nanoparticles that mimic heparan sulfate. Following successful attachment, coronaviruses can enter the cells via direct fusion or by endocytosis. Using mass-spectrometry-based proteomics, we will search for common host proteins involved in coronavirus entry and characterize their interactions with viral proteins. Our results will broaden the knowledge about coronavirus usage of heparan sulfate for attachment to the cells and characterize complex host cell network in coronavirus entry pathways. Furthermore, it can lead to development of heparan sulfate mimicking nanoparticles with virucidal activity and their application as a preventive measure to curb the coronavirus infection.

Název v anglickém jazyce

Characterization and targetint virus-host interaction

Popis výsledku anglicky

Chronic hepatitis is a life-long liver disease caused by infection of Hepatitis B virus (HBV). Despite the existence of preventive vaccine, more than 250 million people worldwide suffer from chronic hepatitis. Current treatment, involving nucleos(t)ide analogs or pegylated interferon-alpha, has many adverse side effects and does not provide functional cure because it is unable to clear HBV from infected cells. HBV is a small enveloped virus that encodes only few viral genes. The replication of the virus entirely relies on host environment and the viral proteins evolved to perform multiple functions. The HBc protein is a perfect example of virus-host interaction that is critical for the establishment and maintenance of persistent infections. While HBc is the main structural component of the viral nucleocapsid, additional regulatory roles of HBc in the viral life cycle and pathogenesis have been described (Fig. 1).The research of Jan Weber’s group is focused on identification of novel core-host interactions and characterization of cellular pathways that play role in HBV-associated pathogenesis1. Another important aspect of the research is to elucidate how various posttranslational modifications, e.g. serine phosphorylation, arginine methylation, ubiquitination or sumoylation, affect the HBc protein stability, intracellular trafficking or interaction with other proteins2,3. Using affinity purification/mass spectrometry assay we identified a pool of potential HBc interacting proteins. Among them, we selected three groups of promising candidates with potential effect on HBV replication: i) host factors with E3 ubiquitin ligase or kinase activities that may regulate HBc posttranslational modifications, e.g. serine phosphorylation or ubiquitin-like modifications, ii) proteins involved in epigenetic modifications, transcriptional control and nucleosome assembly that may affect viral cccDNA formation, activity and maintenance, iii) host chaperone proteins with potential role in viral nucleocapsid formation, pgRNA encapsidation and reverse transcription. The results generated by proposed comprehensive analysis of HBc –host interaction pathways would bring novel knowledge into HBV field and eventually lead to development of new promising anti-HBV therapies.In addition, our group is interested in characterization and targeting coronavirus attachment and entry. The emergence of third coronavirus causing severe acute respiratory syndrome in less than two decades transformed emerging coronaviruses in a new public health concern. Since SARS-CoV-2 detection in Wuhan in late 2019, the virus spread in almost every country, totaling so far 5 million deaths. It became obvious that we need a broad-spectrum intervention, that would halt this and future coronavirus pandemic. One of the best measures is to block virus before it establishes new infection in the cells, thus inhibition of viral attachment and entry are self-evident choices. Many viruses use abundant adhesion molecules such as heparan sulfate proteoglycan at surface for initial attachment to the cells4. We plan to characterize and target this interaction with sulfated nanoparticles that mimic heparan sulfate. Following successful attachment, coronaviruses can enter the cells via direct fusion or by endocytosis. Using mass-spectrometry-based proteomics, we will search for common host proteins involved in coronavirus entry and characterize their interactions with viral proteins. Our results will broaden the knowledge about coronavirus usage of heparan sulfate for attachment to the cells and characterize complex host cell network in coronavirus entry pathways. Furthermore, it can lead to development of heparan sulfate mimicking nanoparticles with virucidal activity and their application as a preventive measure to curb the coronavirus infection.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10607 - Virology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů