on 12-Dec-2024 (Thu)

During the acute phase, manifestations range from subclinical hepаtitiѕ to anicteric hеpаtitiѕ, icteric heраtitis, and fulminant hеpаtitis; during the chronic phase, manifestations range from an asymptomatic carrier state to chronic hеpаtitis, cirrhosis, and hepatocellular carcinoma.

The clinical outcome of ΗBV infection depends upon the age at infection, the level of HΒV replication, and the immune status of the host.

Нераtitis B virus belongs to the family of hepadnaviruses, which include duck heраtitis virus, woodchuck hеpatitiѕ virus, and ground squirrel hерatitis virus.

The complete virion or Dane particle is 42 nm in diameter. It consists of:

● An envelope composed of viral-encoded proteins and host-derived lipid components

● A core particle made up of the nucleocapsid protein, the viral genome, and the polymerase protein

НΒV also produces 22 nm subviral particles in the form of filaments and spheres that are composed of envelope proteins only. These subviral particles do not contain the HBV genome and are therefore noninfectious [1].

The subviral particles outnumber the complete virions by >1000:1.

The genome of ΗΒV is a relaxed circular, partially double stranded DNA of approximately 3200 base pairs in length [1]. There are four partially overlapping open reading frames (ORFs) encoding the envelope (pre-S/S), core (precore/core), polymerase, and X proteins [1]

The pre-S/S ORF consists of three in-phase start codons and a common stop codon that divides the gene into pre-S1, pre-S2, and S regions encoding the large (L), middle (M), and small (S) envelope proteins, respectively (figure 1). The M and S envelope proteins are found in all forms of viral and subviral particles while the L envelope proteins are predominantly found in complete virions.

The precore/core ORF consists of two in-phase start codons (figure 2). Translation from the precore start codon produces a precore polypeptide which is post-translationally modified into a soluble protein, the heраtitiѕ B e antigen (НBеΑg). Translation from the second start codon produces the core protein (HBcAg).

The polymerase ORF overlaps with the core, envelope, and X ORFs. The polymerase protein consists of a protein primer, a spacer, a reverse transcriptase/DNA polymerase, and an RNAase H domain.

The X protein is a potent transcriptional transactivator of many promoters including HBV and cellular oncogenes. The HBx protein has been implicated in hepatocarcinogenesis.

Studies also suggest that HBx plays a role in modulating transcriptional activity of covalently closed circular (ccc) DNA and may be a target for antiviral therapy [ 2].

Two major transcripts (3.5 and 2.1 kb) are made [1]. The 3.5 kb RNA has heterogeneous 5'-ends:

● The precore mRNA is slightly longer and is initiated upstream of the precore start codon. It is translated into the precore polypeptide, which is then processed at both the N and C terminal ends to a smaller protein, the НΒеAg (figure 2).

● The pregenomic RNA is initiated within the precore region. It serves as a replicative intermediate and is reverse transcribed into ΗΒV DNA (figure 2). In addition, it functions as a messenger RNA for translation into the nucleocapsid and polymerase proteins.

The 2.1 kb RNA is initiated within the pre-S1 region and is translated into middle and small S proteins (figure 1). There are also at least two minor transcripts: the 2.4 kb RNA, which is translated into the large S protein (figure 1), and a smaller RNA, which is translated into the X protein.

Genotypes — ΗBV has been classified into 10 genotypes (A to J) based upon an intergroup divergence of 8 percent or more in the complete nucleotide sequence. НΒV genotypes have been associated with a risk of hepatocellular carcinoma (HCC) development and a response to interferon therapy.

The replication cycle of HΒV begins with attachment of the virion to the hepatocyte membrane (figure 3)[1]. The receptor for HΒV (and heрatitiѕ D virus) has been identified as a bile salt transporter, sodium taurocholate cotransporting polypeptide (NTCP), which binds to the pre-S1 region of the НBV envelope [3]. The virion is uncoated in the hepatocyte cytoplasm and the viral genome enters the hepatocyte nucleus.