The Hepatitis B virus (HBV), which belongs to the hepadnavirus family, is a small circular DNA virus containing a nucleocapsid and an envelope. HBV nucleocapsid contains a relatively small and incompletely double stranded 3.2 Kb DNA genome, viral polymerase and core protein. Its envelope is composed of viral surface proteins enclosed by a lipid membrane from host cells. In the serum of infected patients, there are both mature virion with viral DNA and subviral particles without viral DNA .Sub viral particles are overwhelmingly in excess to infectious particles, which is the majority of the two types.
The life cycle of HBV is believed to begin when the virus attaches to the host cell membrane via its envelope proteins. Then, the viral membrane fuses with the cell membrane and the viral genome is released into the cells. After the viral genome reaches the nucleus, the viral polymerase converts the partial double stranded DNA (dsDNA) genome into covalently closed circle DNA (cccDNA). The cccDNA is believed to be the template for further propagation of pre-genomic RNA, which directs the synthesis of viral DNA and mRNA that encode all the viral proteins HBV core particles are assembled in the cytosol following the encapsidation of pre-genomic RNA, which is then degraded during the reverse transcription of pre-genomic RNA into a complementary strand of DNA. HBV surface proteins are initially synthesized and polymerized in the rough endoplasmic reticulum (RER). These proteins are transported to the post ER and pre-Golgi compartments where budding of the nucleocapsid follows . The assembled HBV virion and sub-viral particles are transported to the Golgi for further modification of its glycans in the surface proteins, and then are secreted out of the host cell to finish the life cycle. HBV replication and viral protein synthesis in the infected cells are fairly well elucidated. However, the early steps of HBV infection including of the penetration of virus and release of its genome into host cells is uncertain.
In general, the early step of virus infection in which the virus enters the cell can be divided into three stages: attachment, fusion, and entry. Enveloped viruses usually entry by an attachment to the host cells, which usually is via the interaction of viral surface protein with the specific receptor on the cell membrane. However, the attachment itself does not necessarily result in viral entry. The fusion of a viral envelope and cell membrane and the following viral genome release finally trigger the viral infection. The viral fusion occurs by one of at least two known mechanisms. The first requires a fusion of the viral envelope with the plasma membrane, leading to the release of the viral nucleocapsid. HIV is an example of a virus that uses this type of mechanism to enter . In the second mechanism, an endosomal compartment first takes up the attached virus. Later, the viral genome is released from this endosomal compartment into the cytoplasm by a process that may or may not depend upon a lowering of the pH to activate a virus-mediated fusogenic activity. In some virus/cell systems, such as those involving influenza virus or paramyxoviruses exogenously adding protease generates infective virions from otherwise non-infective ones. The reason is that the proteolysis exposes the viral fusion sequence. The un-coating and the genome release occur instantly after virus fusion. The following transport of the viral genome to nucleus and the start of the virus replication finally complete the early steps of virus life cycle.
The life cycle of HBV is believed to begin when the virus attaches to the host cell membrane via its envelope proteins. Then, the viral membrane fuses with the cell membrane and the viral genome is released into the cells. After the viral genome reaches the nucleus, the viral polymerase converts the partial double stranded DNA (dsDNA) genome into covalently closed circle DNA (cccDNA). The cccDNA is believed to be the template for further propagation of pre-genomic RNA, which directs the synthesis of viral DNA and mRNA that encode all the viral proteins HBV core particles are assembled in the cytosol following the encapsidation of pre-genomic RNA, which is then degraded during the reverse transcription of pre-genomic RNA into a complementary strand of DNA. HBV surface proteins are initially synthesized and polymerized in the rough endoplasmic reticulum (RER). These proteins are transported to the post ER and pre-Golgi compartments where budding of the nucleocapsid follows . The assembled HBV virion and sub-viral particles are transported to the Golgi for further modification of its glycans in the surface proteins, and then are secreted out of the host cell to finish the life cycle. HBV replication and viral protein synthesis in the infected cells are fairly well elucidated. However, the early steps of HBV infection including of the penetration of virus and release of its genome into host cells is uncertain.
In general, the early step of virus infection in which the virus enters the cell can be divided into three stages: attachment, fusion, and entry. Enveloped viruses usually entry by an attachment to the host cells, which usually is via the interaction of viral surface protein with the specific receptor on the cell membrane. However, the attachment itself does not necessarily result in viral entry. The fusion of a viral envelope and cell membrane and the following viral genome release finally trigger the viral infection. The viral fusion occurs by one of at least two known mechanisms. The first requires a fusion of the viral envelope with the plasma membrane, leading to the release of the viral nucleocapsid. HIV is an example of a virus that uses this type of mechanism to enter . In the second mechanism, an endosomal compartment first takes up the attached virus. Later, the viral genome is released from this endosomal compartment into the cytoplasm by a process that may or may not depend upon a lowering of the pH to activate a virus-mediated fusogenic activity. In some virus/cell systems, such as those involving influenza virus or paramyxoviruses exogenously adding protease generates infective virions from otherwise non-infective ones. The reason is that the proteolysis exposes the viral fusion sequence. The un-coating and the genome release occur instantly after virus fusion. The following transport of the viral genome to nucleus and the start of the virus replication finally complete the early steps of virus life cycle.
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