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The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion


Hepatitis B virus (HBV) is an important human pathogen. Chronic infection with HBV can lead to cirrhosis and liver cancer. While HBV infection is treatable, it remains a challenge to eradicate the virus in patients. HBV can produce various particles with different sizes and morphologies. Virions are complete particles with both nucleocapsids and surface antigen (HBsAg) envelope. In addition to DNA-containing virions, HBV produced incomplete particles, including HBsAg particles without nucleocapsids, naked capsid particles without the HBsAg envelope, and empty virions containing both HBsAg envelope and empty capsids. It remains unclear how these various HBV particles are exported from the liver. We identified many host factors known to be involved in a membrane trafficking machinery (so-called ESCRT), as well as required for HBV replication. Interestingly, aberrant expression of HGS (an ESCRT-0 factor) can inhibit HBV replication. However, unexpectedly, HGS could boost the release of naked capsids, while concurrently reduced the extracellular virions and HBsAg particles. HGS can associate and co-localize with HBV capsid protein. In summary, our work demonstrated that an appropriate level of HGS is important for HBV propagation. We entertain the possibility that HGS and other ESCRT factors may be further developed into a therapeutic treatment for hepatitis B.


Vyšlo v časopise: The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005123
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005123

Souhrn

Hepatitis B virus (HBV) is an important human pathogen. Chronic infection with HBV can lead to cirrhosis and liver cancer. While HBV infection is treatable, it remains a challenge to eradicate the virus in patients. HBV can produce various particles with different sizes and morphologies. Virions are complete particles with both nucleocapsids and surface antigen (HBsAg) envelope. In addition to DNA-containing virions, HBV produced incomplete particles, including HBsAg particles without nucleocapsids, naked capsid particles without the HBsAg envelope, and empty virions containing both HBsAg envelope and empty capsids. It remains unclear how these various HBV particles are exported from the liver. We identified many host factors known to be involved in a membrane trafficking machinery (so-called ESCRT), as well as required for HBV replication. Interestingly, aberrant expression of HGS (an ESCRT-0 factor) can inhibit HBV replication. However, unexpectedly, HGS could boost the release of naked capsids, while concurrently reduced the extracellular virions and HBsAg particles. HGS can associate and co-localize with HBV capsid protein. In summary, our work demonstrated that an appropriate level of HGS is important for HBV propagation. We entertain the possibility that HGS and other ESCRT factors may be further developed into a therapeutic treatment for hepatitis B.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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