Structure and Molecular Virology

Kann, Michael; Gerlich, Wolfram H.

doi:10.1002/9780470987131.ch10

Cited by 20 publications

(63 citation statements)

References 266 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The correlation of genome maturation and phosphorylation may be explained by the inhibition of phosphorylation caused by RNA bound to the C-terminal sites that are phosphorylated (6). The residual phosphorylation observed for ImmatC-Inh is in accordance with the report that specific encapsidation of the PG with polymerase requires at least some phosphorylated capsid subunits (36), which may reflect a selection of capsid subunits interacting with the kinase.…”

Section: Discussionsupporting

confidence: 86%

“…They replicate via a pregenomic RNA (PG) synthesized in the nucleus of the infected cell. After export from the nucleus to the cytosol, the PG is trapped within a newly formed isometric capsid (core particle) together with a cellular protein kinase (5)(6)(7)(8)(9)(10). The shell of the capsid contains 180 or 240 identical capsid protein subunits of 21.5 kDa (11).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Nuclear import of hepatitis B virus capsids and release of the viral genome

Rabe

Vlachou

Panté

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

259

262

View full text Add to dashboard Cite

While studying the import of the hepatitis B virus genome into the nucleus of permeabilized tissue culture cells, we found that viral capsids were imported in intact form through the nuclear pore into the nuclear basket. Import depended on phosphorylation of the capsid protein and was mediated by the cellular transport receptors importin ␣ and ␤. Virus-derived capsids that contained the mature viral genome were able to release the viral DNA and capsid protein into the nucleoplasm. The uncoating reaction was independent of Ran, a GTP-binding enzyme responsible for dissociating other imported cargoes from the inner face of the nuclear pore. Immature capsids that did not contain the mature viral genome reached the basket but did not release capsid proteins nor immature genomes into the nucleoplasm. The different fate of mature and immature capsids after passing the nuclear pore indicates that the outcome of a nuclear import event may be regulated within the nuclear basket.

show abstract

Section: Discussionsupporting

confidence: 86%

mentioning

confidence: 99%

Nuclear import of hepatitis B virus capsids and release of the viral genome

Rabe

Vlachou

Panté

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

259

262

View full text Add to dashboard Cite

show abstract

“…A tantalizing hypothesis suggested by these results is that the hepadnaviral maturation signal, originating with the production of mature dsDNA within the NC, is transmitted through the NC shell in the form of the complete dephosphorylation of the core CTD, and is ultimately relayed from the dephosphorylated NC to the viral surface proteins. Also consistent with this notion are the reports that changes in the core phosphorylation state can affect its nucleic acid binding properties (51,52), which may act to sense and transmit information on the nature of the nucleic acid within the maturing NC. However, evidence is still lacking in support of a direct role for mature NC dephosphorylation in triggering envelopment.…”

Section: Discussionsupporting

confidence: 62%

Reverse transcription-associated dephosphorylation of hepadnavirus nucleocapsids

Perlman

Berg

O’Connor

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

113

172

View full text Add to dashboard Cite

Hepatitis B viruses are pararetroviruses that contain a partially dsDNA genome and replicate this DNA through an RNA intermediate (the pregenomic RNA, pgRNA) by reverse transcription. Viral assembly begins with the packaging of the pgRNA into nucleocapsids (NCs), with subsequent reverse transcription within NCs converting the pgRNA into the characteristic dsDNA genome. Only NCs containing this dsDNA (the so-called ''mature'' NCs) are enveloped by the viral envelope proteins and secreted as virions; ''immature'' NCs, i.e., those containing pgRNA or immature reverse transcription intermediates, are excluded from virion formation. This phenomenon is thought to be caused by the emergence of an intrinsic maturation signal only on the mature NCs. To define the maturation signal, we have devised a method to separate mature from immature duck hepatitis B virus NCs and have compared them to NCs derived from secreted virions. Detailed mass spectrometric analyses revealed that the core protein from immature NCs was phosphorylated on at least six sites, whereas the core protein from mature NCs and that from secreted virions was entirely dephosphorylated. These results, together with the known requirement of core phosphorylation for pgRNA packaging and DNA synthesis, suggest that the NC undergoes a dynamic change in phosphorylation state to fulfill its multiple roles at different stages of viral replication. Although phosphorylation of the NCs is required for efficient RNA packaging and DNA synthesis by the immature NCs, dephosphorylation of the mature NCs may trigger envelopment and secretion.hepatitis B virus ͉ viral maturation ͉ posttranslational modification ͉ tandem mass spectrometry ͉ vibrational cooling MALDI-Fourier transform MS H epatitis B viruses (HBVs), or hepadnaviruses, are pararetroviruses that replicate their DNA genome via an RNA intermediate (pregenomic RNA, pgRNA) by reverse transcription (1, 2). Similar to classical retroviruses, hepadnaviruses begin assembly with the formation of intracellular nucleocapsid (NC) particles that specifically package viral pgRNA. However, they undergo reverse transcription before membrane envelopment of NCs and secretion as virions, rather than subsequent to entry into new target cells, like classical retroviruses (2, 3). This replication strategy is manifested in the hepadnaviral maturation phenomenon: secreted hepadnaviral virions contain only the mature, double-stranded relaxed circular (or the mature, doublestranded linear) DNA species, whereas intracellular pools of NCs contain a mix of nucleic acid species, including the pgRNA and DNA species from all of the intermediate stages of reverse transcription (2).The maturation phenomenon implies that mature DNAcontaining NCs may be selectively enveloped and secreted. It was proposed that DNA synthesis and NC envelopment may be coupled through a maturation signal (2). Strong support for this maturation signal model has been obtained (4-6), particularly through the use of a synchronized duck HBV (DHBV) replication system (7,8)...

show abstract

“…The influence of the genotype on the response to antiviral therapy is less clear, but it appears that there are differences among HBV genotypes, e.g. to the response to IFN-α, where patients infected with genotypes A and B tend to respond better than patients infected with genotypes C and D. A similar picture seems to emerge for therapy with lamivudine, where patients infected with genotype B seem to have better response rates than patients infected with genotype C. Although the data provided thus far clearly point to differences in severity and progression of the disease depending on the HBV strain, further systematic analysis is needed to substantiate these indications [44,45,51,52,[164][165][166].…”

Section: Hbv Serotypes and Genotypesmentioning

confidence: 80%

“…Expression of full-length HBx protein is important for in vivo infectivity [57]. It acts as a transcriptional activator of several viral and cellular promoters through direct interaction with cellular transcription factors and is also involved in the activation of signal transduction cascades [51,52]. Indications are provided by some authors that the HBx protein might play a role in the development of HBV-mediated carcinogenesis and thus HCC [58].…”

Section: Hepatitis B: the Virusmentioning

confidence: 99%

Hepatitis B: Where Are We Today?

Eckert¹,

Struff

2006

Transfus Med Hemother

View full text Add to dashboard Cite

Hepatitis B still is a major challenge of modern medicine. Here, we summarize the disease, the life cycle of the virus, the emergence of drug-resistant mutant strains and resulting consequences for new drug development. Hepatitis B has a worldwide prevalence of 0.1-20%. It occurs in an acute and a chronic phase. The acute phase is characterized by viral replication, onset of immune response leading to destruction of infected hepatocytes and, in most cases, viral clearance and lifelong immunity. Clinical symptoms are observed in this phase. The chronic phase is characterized by lifelong persistence of the virus, often without clinical symptoms but bearing the risk of hepatic cirrhosis or hepatocellular carcinoma. Both phases are distinguished by detection of viral antigens and hepatitis B antibodies in the blood. The hepatitis B virus (HBV) shows several features unique for hepadnaviridae: i) formation of covalently closed-circle DNA (cccDNA) as template for viral DNA replication and synthesis of viral RNAs and ii) a reverse transcription step in the synthesis of new viral DNAs. These features are the prime targets in antiviral drug development. Unfortunately, with the exception of interferon, resistant mutant strains of HBV were found after widespread use of every new drug so far. Therefore, combination therapies aimed at different targets are being discussed so that the selective pressure can no longer be compensated by HBV. This paper is the first part of a trilogy concerning HBV which will also discuss the situation regarding transplantation (second part) and blood transfusion (third part).

show abstract

Structure and Molecular Virology

Cited by 20 publications

References 266 publications

Nuclear import of hepatitis B virus capsids and release of the viral genome

Nuclear import of hepatitis B virus capsids and release of the viral genome

Reverse transcription-associated dephosphorylation of hepadnavirus nucleocapsids

Hepatitis B: Where Are We Today?

Contact Info

Product

Resources

About