Molecular biology of hepatitis B virus infection

Abstract

Human hepatitis B virus (HBV) is the prototype of a family of small DNA viruses that productively infect hepatocytes, the major cell of the liver, and replicate by reverse transcription of a terminally redundant viral RNA, the pregenome. Upon infection, the circular, partially double-stranded virion DNA is converted in the nucleus to a covalently closed circular DNA (cccDNA) that assembles into a minichromosome, the template for viral mRNA synthesis. Infection of hepatocytes is non-cytopathic. Infection of the liver may be either transient (<6 months) or chronic and life long, depending on the ability of the host immune response to clear the infection. Chronic infections can cause immune mediated liver damage progressing to cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of carcinogenesis are unclear. Antiviral therapies with nucleoside analog inhibitors of viral DNA synthesis delay sequelae, but cannot cure HBV infections due to the persistence of cccDNA in hepatocytes.

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…The small (3.2 kb), partially double-stranded, relaxedcircular (rc) DNA features 4 open reading frames encoding 7 proteins: HBeAg (HBV e antigen, secreted dimeric protein), HBcAg (HBV core antigen, viral capsid protein), HBV Pol/RT (polymerase, reverse transcriptase activity), PreS1/PreS2/HBsAg (large, medium, and small surface envelope glycoproteins), and HBx (HBV x antigen, regulator of transcription required for the initiation of infection). 11,12 Upon viral uptake into hepatocytes, the HBV nucleocapsid is transported to the nucleus to release the rcDNA genome. In the nucleoplasm, the rcDNA is converted into a covalently closed circular DNA (cccDNA), which is wrapped by histones to form an episomal chromatinized structure.…”

“…The DNA containing nucleocapsids in the cytoplasm are either recycled into the nucleus to maintain cccDNA reservoir, or enveloped and secreted via the endoplasmic reticulum. 11 In addition to complete infectious virions (diameter of 42 nm), infected cells produce a large excess of genome-free, non-infectious sub-viral spherical or filamentous particles of 22 nm. 11 Viral genome integration in the host genome can occur randomly; it is not required for viral replication, but is one of the important mechanisms involved in hepatocyte transformation.…”

Hepatite B e C: diagnóstico e tratamento

“…Este DNA é responsável pelo estabelecimento da doença crônica do HBV à medida que adquire componentes do hospedeiro para formar minicromossomo. HBV transcreve proteínas e moléculas de RNA através da enzima trasncriptase reversa, que sintetizaram novas cadeias do DNA, que adquirem membranas lipídicas através do complexo de Golgi e são colocadas para fora da superfície da célula hospedeira 35 . Assim, o HBV segue este ciclo de vida complexo envolvendo transcrição reversa semelhante aos retrovírus, ao contrário dos vírus de DNA.…”

Anti-hepatitis B viral activity of <i>Phyllanthus niruri</i> L (Phyllanthaceae) in HepG2/C3A and SK-HEP-1 cells

“…Despite their potential, few natural herbs have been evaluated in a systematic manner. The goals of HBV treatment are to prevent development of HCC and cirrhosis, regulate alkaline transaminase (ALT) levels, suppress viral replication, and reduce the liver damage in HBeAg-negative as well as with HBeAg-positive individuals [8].…”