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Heparin at physiological concentration can enhance PEG-free in vitro infection with human hepatitis B virus.

ABSTRACT: Hepatitis B virus (HBV) is a blood-borne pathogen responsible for chronic hepatitis, cirrhosis, and liver cancer. The mechanism of HBV entry into hepatocytes remains to be investigated. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was discovered as a major HBV receptor based on an in vitro infection system using NTCP-reconstituted HepG2 cells. However, this infection system relies on the compound polyethylene glycol (4% PEG), which is not physiologically relevant to human infection. High concentration of heparin has been commonly used as an inhibitor control for in vitro infection in the field. Surprisingly, we found that heparin at physiological concentration can enhance HBV infection in a PreS1-peptide sensitive, NTCP-dependent manner in both HepaRG and HepG2-NTCP-AS cells. O-sulfation of heparin is more important for the infection enhancement than N-sulfation. This system based on the HepG2-NTCP-AS cells can support in vitro infection with HBV genotypes B and C, as well as using serum samples from HBeAg positive and negative chronic carriers. In summary, our study provides a PEG-free infection system closely resembling human natural infection. In addition, it points to a future research direction for heparin and heparin-binding host factor(s) in the blood, which are potentially involved in viral entry. To our knowledge, this is the first soluble and circulatory host factor which can enhance HBV in vitro infection.

SUBMITTER: Choijilsuren G

PROVIDER: S-EPMC5663848 | biostudies-other | 2017 Oct

REPOSITORIES: biostudies-other

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Heparin at physiological concentration can enhance PEG-free in vitro infection with human hepatitis B virus.

Choijilsuren Gansukh G Jhou Ren-Shiang RS Chou Shu-Fan SF Chang Ching-Jen CJ Yang Hwai-I HI Chen Yang-Yuan YY Chuang Wan-Long WL Yu Ming-Lung ML Shih Chiaho C

Scientific reports 20171031 1

Hepatitis B virus (HBV) is a blood-borne pathogen responsible for chronic hepatitis, cirrhosis, and liver cancer. The mechanism of HBV entry into hepatocytes remains to be investigated. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was discovered as a major HBV receptor based on an in vitro infection system using NTCP-reconstituted HepG2 cells. However, this infection system relies on the compound polyethylene glycol (4% PEG), which is not physiologically relevant to human infe ...[more]

PMID: 29089529

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Dataset Information

Heparin at physiological concentration can enhance PEG-free in vitro infection with human hepatitis B virus.

Publications

Heparin at physiological concentration can enhance PEG-free in vitro infection with human hepatitis B virus.

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