Anti-Hbv

Background


Hepatitis is a general term meaning inflammation of the liver. It can be caused by a variety of different viruses such as hepatitis A, B, C, D and E viruses. And the most common types are Hepatitis A, Hepatitis B, and Hepatitis C. Hepatitis B virus (HBV) is the prototype member of the family Hepadnaviridae.

HBV is the smallest hepadnavirus of about 42 nm in diameter, which has a partially double-stranded circular DNA genome of 3.2 kb. The viral genome together with the viral polymerase are packed inside the nucleocapsid core (HBeAg), surrounded by an outer lipoprotein coat (envelope) containing the surface antigen (HBsAg). Compared to other human viruses, HBV is unusual in that it contained a vast excess of noninfectious subviral particles composed only of viral surface proteins and lipids, appear predominantly as 22 nm spheres and filaments with a diameter of 22 nm. HBV DNA is a relaxed circular, partially double-stranded molecule of 3.2 kb. The positive strand DNA is less than unit length and of variable length. The viral polymerase can repair this gap and generate a fully duplex genome. It contains four partially overlapping open-reading frames (ORFs) which are responsible for the transcription and expression of seven different hepatitis B proteins.

Although mutations can occur randomly along the HBV genome, the overlapping genes of HBV limit the number and location of viable mutants. Despite HBV is a DNA virus, its replication is through an RNA-replicative intermediate requiring an active viral reverse transcriptase/polymerase enzyme. However, the enzyme is believed to lack a 3' to 5' exonuclease proofreading capacity. The mutation rate of HBV is approximately 2 ×10-4 base substitutions/site/year, which seems to be 10-fold higher than that of other DNA viruses. As a result, HBV has a "quasispecies" distribution in infected individuals which implies that HBV circulates as a mixture of genetically distinct but closely related variants that are in equilibrium at a given time point of infection in a given replicative environment. The quasispecies distribution of HBV implies that any newly generated mutations would give a selective advantage to the virus in a given replicative environment that allows the corresponding viral population to overtake the other variants. Under particular selection pressure, both endogenous (host immune clearance) and exogenous (vaccine and antivirals), strongly influence the predominant HBV quasispecies in an infected individual. The fittest virus, i.e. the virus that replicates best, becomes dominant species. Viruses encoding changes associated with antiviral resistance often have reduced replication in vitro, but the accumulation of additional mutations helps restore viral fitness. These compensatory mutations may occur not only in the polymerase gene, but also in other genes such as overlapping envelop gene, the precore gene or in regulatory regions such as the basal core promoter.

According to overall nucleotide sequence variation of the genome, HBV has been classified into eight different genotypes, designated A through H based on inter-group divergence of 8% or greater in the entire genomic nucleotide sequences. Each genotype has a distinct geographical distribution. Genotype A is prevalent in Northwestern Europe, North America and Africa. Genotypes B and C are found in Southeast Asia, China, Japan and Korea. Genotype D, which can be distinguished into four subgenotypes, Dl–D4 is spread worldwide but is predominant in the Mediterranean region. Genotype E is found in East Africa and genotype F is mainly found in the New World. Genotype G was identified in France, America and Ger many. Genotype H was identified recently among the Amerindians. At the same time, The virus is divided into four major serotypes (adr, adw, ayr, ayw) based on antigenic epitopes presented on its envelope proteins.

Symptoms of acute HBV include fatigue, loss of appetite, fever, nausea, vomiting, abdominal pain, clay-colored bowel movement, dark urine, joint pain, and then progresses to development of jaundice. Unfortunately, Most babies exposed to this virus never have signs and symptoms. Meanwhile the patient are more likely to become carriers of hepatitis B for life because their immune system is unable to fight and clear the virus from their body. Then the other people who has not HBV can become infected with the virus during activities such as birth (spread from an infected mother to her baby during birth), sex with an infected partner, sharing items such as razors or toothbrushes with an infected person, direct contact with the blood or open sores of an infected person, sharing needles, syringes, or other drug-injection equipment, exposure to blood from needlesticks or other sharp instruments and so on. Although none of the available drugs can clear the infection, three kinds of drugs can stop the virus from replicating, thus minimizing liver damage. The first is antiviral medications including lamivudine, adefovir, telbivudine, and entecavir, which can help fight the virus and slow its ability to damage your liver. The second is interferon. The last one is liver-protective medication through decrease the transaminase in liver. Such as bifendate. But when the liver was severely damaged, a liver transplant may be an option.

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