Hepatitis B virus (HBV) is a highly pathogenic virus that causes chronic liver diseases in millions of people globally. In addition to a symptomatic, serologically evident infection, occult persistent HBV carriage has...Hepatitis B virus (HBV) is a highly pathogenic virus that causes chronic liver diseases in millions of people globally. In addition to a symptomatic, serologically evident infection, occult persistent HBV carriage has been identified since nucleic acid amplification assays of enhanced sensitivity became introduced for detection of hepadnaviral genomes and their replicative intermediates. Current evidence indicates that occult HBV infection is a common and long-term consequence of resolution of acute hepatitis B. This form of residual infection is termed as secondary occult infection (SOI). The data from the woodchuck model of HBV infection indicate that exposure to small amounts of hepadnavirus can also cause primary occult infection (POI) where virus genome, but no serological makers of exposure to virus, are detectable, and the liver may not be involved. However, virus replicates at low levels in the lymphatic system in both these forms. We briefly summarize the current understanding of the nature and characteristics of occult hepadnaviral persistence as well as of its documented and expected pathological consequences.展开更多
The nucleocapsid of hepadnaviruses consisits of dimers of the core proteins. However, the mechanism of the core-core subunit interaction is not well understood. The Nterminus of the core protein of woodchuck hepatitis...The nucleocapsid of hepadnaviruses consisits of dimers of the core proteins. However, the mechanism of the core-core subunit interaction is not well understood. The Nterminus of the core protein of woodchuck hepatitis virus(WHV) was found containing four conserved hydrophobic amino acid residues (from residue 101 to 122 ). These residues, referred to the hydrophobic heptad repeat(hhr), distributed as heptad repeats in the primary sequence. Since hydrophobic bounds often play an important role in interaction of proteins, roles of the hhr region in capsid assembly of WHV were investigated using a cell culture system. The codons for these four hydrophobic amino acid residues and other related residues in this region were substituted with codons specifying alanine or proline. Phenotype of each of these mutants was examined at various stages of viral replication in Hub7 cells. It was found that single substitution of the four hydrophobic residues had no detectable effect, but substitution of the same residues in various paired combinations resulted in a complete inhibition of capsid assembly. The capsid assembly was inhibited when amino acid insertion occerred at the first and last two hydrophobic residues or a single amino acid deletion occurred at the first pair of hydrophobic residues. However, random amino acid substitutions in this region did not affect assembly. The results indicated that the hhr region of the core protein was necessory for capsid assembly of woodchuck hepatitis virus.展开更多
基金operating research grants from the Canadian Institutes of Health Research, Canada and the Canada Research Chair Program, and the Canada Foundation for Innovation
文摘Hepatitis B virus (HBV) is a highly pathogenic virus that causes chronic liver diseases in millions of people globally. In addition to a symptomatic, serologically evident infection, occult persistent HBV carriage has been identified since nucleic acid amplification assays of enhanced sensitivity became introduced for detection of hepadnaviral genomes and their replicative intermediates. Current evidence indicates that occult HBV infection is a common and long-term consequence of resolution of acute hepatitis B. This form of residual infection is termed as secondary occult infection (SOI). The data from the woodchuck model of HBV infection indicate that exposure to small amounts of hepadnavirus can also cause primary occult infection (POI) where virus genome, but no serological makers of exposure to virus, are detectable, and the liver may not be involved. However, virus replicates at low levels in the lymphatic system in both these forms. We briefly summarize the current understanding of the nature and characteristics of occult hepadnaviral persistence as well as of its documented and expected pathological consequences.
文摘The nucleocapsid of hepadnaviruses consisits of dimers of the core proteins. However, the mechanism of the core-core subunit interaction is not well understood. The Nterminus of the core protein of woodchuck hepatitis virus(WHV) was found containing four conserved hydrophobic amino acid residues (from residue 101 to 122 ). These residues, referred to the hydrophobic heptad repeat(hhr), distributed as heptad repeats in the primary sequence. Since hydrophobic bounds often play an important role in interaction of proteins, roles of the hhr region in capsid assembly of WHV were investigated using a cell culture system. The codons for these four hydrophobic amino acid residues and other related residues in this region were substituted with codons specifying alanine or proline. Phenotype of each of these mutants was examined at various stages of viral replication in Hub7 cells. It was found that single substitution of the four hydrophobic residues had no detectable effect, but substitution of the same residues in various paired combinations resulted in a complete inhibition of capsid assembly. The capsid assembly was inhibited when amino acid insertion occerred at the first and last two hydrophobic residues or a single amino acid deletion occurred at the first pair of hydrophobic residues. However, random amino acid substitutions in this region did not affect assembly. The results indicated that the hhr region of the core protein was necessory for capsid assembly of woodchuck hepatitis virus.
