Hepatitis B causes: Difference between revisions

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* HBcAg is the most conserved [[polypeptide]] among the mammalian [[hepadnaviruses]] with 68% homology between [[HBV]] and GSHV and 92% between GSHV and WHV. Furthermore, it plays important roles in the encapsidation of the viral pregenomic [[RNA]]. The [[polymerase]] protein is quite immunogenic during both acute and chronic infection.<ref name=WHO>{{cite web | title = Hepatitis B | url = http://www.who.int/csr/disease/hepatitis/HepatitisB_whocdscsrlyo2002_2.pdf }}</ref>
* HBcAg is the most conserved [[polypeptide]] among the mammalian [[hepadnaviruses]] with 68% homology between [[HBV]] and GSHV and 92% between GSHV and WHV. Furthermore, it plays important roles in the encapsidation of the viral pregenomic [[RNA]]. The [[polymerase]] protein is quite immunogenic during both acute and chronic infection.<ref name=WHO>{{cite web | title = Hepatitis B | url = http://www.who.int/csr/disease/hepatitis/HepatitisB_whocdscsrlyo2002_2.pdf }}</ref>


===Serotypes and Genotypes ===
The [[virus]] is divided into:
* Four major [[serotype]]s (adr, adw, ayr, ayw) based on antigenic [[epitope]]s presented on its envelope [[proteins]]
* Ten [[genotype]]s (A-J) according to overall [[nucleotide]] sequence variation of the [[genome]]
The genotypes have a distinct geographical distribution and are used in tracing the evolution and transmission of the virus.
Differences between [[genotype]]s affect:<ref name="pmid15752827">{{cite journal |author=Kramvis A, Kew M, François G |title=Hepatitis B virus genotypes |journal=[[Vaccine]] |volume=23 |issue=19 |pages=2409–23 |year=2005 |month=March |pmid=15752827 |doi=10.1016/j.vaccine.2004.10.045 |url=http://linkinghub.elsevier.com/retrieve/pii/S0264-410X(04)00849-7 |accessdate=2012-02-08}}</ref><ref name="pmid8666521">{{cite journal |author=Magnius LO, Norder H |title=Subtypes, genotypes and molecular epidemiology of the hepatitis B virus as reflected by sequence variability of the S-gene |journal=[[Intervirology]] |volume=38 |issue=1-2 |pages=24–34 |year=1995 |pmid=8666521 |doi= |url= |accessdate=2012-02-08}}</ref><ref name="pmid21199523">{{cite journal| author=Lin CL, Kao JH| title=The clinical implications of hepatitis B virus genotype: Recent advances. | journal=J Gastroenterol Hepatol | year= 2011 | volume= 26 Suppl 1 | issue=  | pages= 123-30 | pmid=21199523 | doi=10.1111/j.1440-1746.2010.06541.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21199523  }} </ref>
* Outcome (worst in genotype C)
* Seroconversion (lower in genotype C)
* Tendency to chronicity (higher in genotype A)
* Likelihood of [[complications]] (higher in genotype C)
* Response to treatment and possibly [[vaccination]] (better response to [[IFN]] therapy in [[genotype]]s A and B. No association was found between [[genotype]]s and response to [[nucleoside]]s or [[nucleotide]]s)


==Structure==
==Structure==

Revision as of 13:58, 6 August 2015

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

The hepatitis B virus is an hepadnavirus with a DNA genome. The viral particle consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of protein. The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity. It shows tropism for hepatocytes and humans are its only natural reservoir.

Taxonomy

Viruses; Retro-transcribing viruses; Hepadnaviridae; Orthohepadnavirus

Biology

Hepatitis B virions Courtesy: World Health Organization[1]
The genome organisation of HBV. The genes overlap. Courtesy: [Wikimedia Commons][2]

The hepatitis B virus, an hepadnavirus, is a 42 nm partially double stranded DNA virus, composed of a 27 nm nucleocapsid core (HBcAg), surrounded by an outer lipoprotein coat (also called envelope) containing the surface antigen (HBsAg).

Hepatocytes infected in vivo by hepadnaviruses produce an excess of noninfectious viral lipoprotein particles.

Genome

  • HBV virion DNA is a relaxed circular, partially duplex molecule of 3.2 kb, whose circularity is maintained by 5' cohesive ends.[3]
  • A virion-associated polymerase can repair gaps and generate a fully duplex genome. Negative strand DNA is the template for the synthesis of the viral mRNA transcripts. HBV DNA has a very compact coding organization with four partially overlapping open reading frames (ORFs) that are translated into seven known proteins.[3]
  • Noncoding regions are not present.[3]
  • Four separate viral promoters have been identified, driving expression of:[3]
  • Genomic, P, and pre-C and C RNAs
  • L protein mRNA
  • M and S protein mRNAs
  • X protein mRNA

They are referred to as the genomic, pre-S1, S, and X promoters, respectively.

  • Two major classes of transcripts exist:
  • The subgenomic RNAs function exclusively as messenger RNAs (mRNAs) for translation of envelope and X proteins.
  • The genomic RNAs are bifunctional, serving as both the templates for viral DNA synthesis and as messages for ORF pre-C, C, and P translation.[3][4]
  • ORF P encodes the viral polymerase and the terminal protein found on minus strand DNA. ORF C encodes the structural protein of the nucleocapsid and the HBeAg, and ORF S/pre-S encodes the viral surface glycoproteins. The product of ORF X is a poorly understood regulatory protein that enhances the expression of heterologous and homologous cellular genes in trans.
  • The three envelope glycoproteins are not distributed uniformly among the various HBV particle types. Subviral 22 nm particles are composed predominantly of S proteins, with variable amounts of M proteins and few or no L proteins. Virus particles are enriched for L proteins. L proteins carry the receptor recognition domain, which allows efficient binding to cell surface receptors.
  • HBcAg is the most conserved polypeptide among the mammalian hepadnaviruses with 68% homology between HBV and GSHV and 92% between GSHV and WHV. Furthermore, it plays important roles in the encapsidation of the viral pregenomic RNA. The polymerase protein is quite immunogenic during both acute and chronic infection.[3]


Structure

Hepatitis B virus (HBV) is a member of the Hepadnavirus family.[5]

The viral particle (virion) consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of protein. The nucleocapsid encloses the viral DNA and a DNA polymerase, that has reverse transcriptase activity.[6]

The outer envelope contains embedded proteins that are involved in viral binding of, and entry into, susceptible cells. The virus is one of the smallest enveloped animal viruses, with a virion diameter of 42nm, but pleomorphic forms exist, including filamentous and spherical bodies lacking a core. These particles are not infectious and are composed of the lipid and protein that form part of the surface of the virion, which is called the surface antigen (HBsAg), and is produced in excess during the life cycle of the virus.[7]

The protein of the virion coat is termed "surface antigen" or HBsAg. It is sometimes extended as a tubular tail on one side of the virus particle. The surface antigen is generally produced in vast excess, and is found in the blood of infected individuals in the form of filamentous and spherical particles. Filamentous particles are identical to the virion "tails" - they vary in length and have a mean diameter of about 22nm. They sometimes display regular, non-helical transverse striations.[3]

Tropism

Hepatitis B virus shows tropism for hepatocytes.[3]

Natural Reservoir

The natural reservoir for hepatitis B virus is man. Closely related hepadnaviruses have been found in woodchucks and ducks, but they are not infectious for humans.[8]

References

  1. "http://www.who.int/en/". External link in |title= (help)
  2. "http://commons.wikimedia.org/wiki/File:HBV_Genome.svg". External link in |title= (help)
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 "Hepatitis B" (PDF).
  4. Plotkin, Stanley (1999). Vaccines. Philadelphia: W.B. Saunders Co. ISBN 0721674437.
  5. Zuckerman AJ (1996). "Hepatitis Viruses". In Baron S; et al. Baron's Medical Microbiology (4th ed.). University of Texas Medical Branch. ISBN 0-9631172-1-1.
  6. Locarnini S (2004). "Molecular virology of hepatitis B virus". Seminars in Liver Disease. 24 Suppl 1: 3–10. doi:10.1055/s-2004-828672. PMID 15192795. Retrieved 2012-02-08.
  7. Howard CR (1986). "The biology of hepadnaviruses". The Journal of General Virology. 67 ( Pt 7): 1215–35. PMID 3014045. Retrieved 2012-02-08. Unknown parameter |month= ignored (help)
  8. "Hepatitis B".

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