Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The liver is a target for many infectious agents, most notably hepatitis viruses. However, several receptor molecules identified so far for hepatitis viruses were found to be ubiquitously expressed and can thus not account for efficient liver targeting. Using a model hepatitis B virus, the duck hepatitis B virus (DHBV), we have obtained data indicating that scavenging liver sinusoidal endothelial cells (LSEC), rather than hepatocytes themselves, play the key role in the initial uptake of viral pathogens into the liver. Experiments with fluorescent viral particles and coated gold particles in test animals, as well as in primary liver cell culture, demonstrated a preferential uptake of the viral substrates into LSEC. Intracellularly, fluorescent virus particles internalized by LSEC colocalized with the DHBV receptor, carboxypeptidase D, suggesting receptor-mediated rescue from lysosomal degradation. To comply with the high efficiency by which hepatitis B viruses infect hepatocytes in vivo, we propose that viruses initially scavenged by LSEC are thereafter released to infect adjacent hepatocytes, the only cells capable of replicating these viruses. Such a model of primary uptake into LSEC may illustrate a general mechanism by which blood-borne hepatotropic agents are targeted to the hepatocytes in the liver.
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PMID:Endothelial cell-mediated uptake of a hepatitis B virus: a new concept of liver targeting of hepatotropic microorganisms. 1158 79

Hepatitis B virus (HBV) is the prototype of hepatotropic DNA viruses (hepadnaviruses) infecting a wide range of human and non-human hosts. Previous studies with duck hepatitis B virus (DHBV) identified duck carboxypeptidase D (dCPD) as a host specific binding partner for full-length large envelope protein, and p120 as a binding partner for several truncated versions of the large envelope protein. p120 is the P protein of duck glycine decarboxylase (dGLDC) with restricted expression in DHBV infectible tissues. Several lines of evidence suggest the importance of dCPD, and especially p120, in productive DHBV infection, although neither dCPD nor p120 cDNA could confer susceptibility to DHBV infection in any cell line. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a binding partner for the N-terminus of HBV large envelope protein. Importantly, knock down and reconstitution experiments unequivocally demonstrated that NTCP is both necessary and sufficient for in vitro infection by HBV and hepatitis delta virus (HDV), an RNA virus using HBV envelope proteins for its transmission. What remains unclear is whether NTCP is the major HBV receptor in vivo. The fact that some HBV patients are homozygous with an NTCP mutation known to abolish its receptor function suggests the existence of NTCP-independent pathways of HBV entry. Also, NTCP very likely mediates just one step of the HBV entry process, with additional co-factors for productive HBV infection still to be discovered. NTCP offers a novel therapeutic target for the control of chronic HBV infection.
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PMID:From DCPD to NTCP: the long journey towards identifying a functional hepatitis B virus receptor. 2652 64