Assembly Pathway of Hepatitis B Core Virus-like Particles from Genetically Fused Dimers

Holmes, Kris; Shepherd, Dale A.; Ashcroft, Alison E.; Whelan, Mike; Rowlands, David J.; Stonehouse, Nicola J.

doi:10.1074/jbc.m114.622035

Cited by 25 publications

(27 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Assembly has been proposed to begin, at least in vitro, with the formation of a nucleus, a triangular trimer-of-dimers, and then to proceed by the addition of further dimers [13,14]. Early assembly intermediates, while detected by mass spectrometry [15][16][17], have not been structurally characterized.…”

Section: Introductionmentioning

confidence: 99%

Expression of quasi-equivalence and capsid dimorphism in the Hepadnaviridae

Watts

Cheng

et al. 2020

PLoS Comput Biol

View full text Add to dashboard Cite

Hepatitis B virus (HBV) is a leading cause of liver disease. The capsid is an essential component of the virion and it is therefore of interest how it assembles and disassembles. The capsid protein is unusual both for its rare fold and that it polymerizes according to two different icosahedral symmetries, causing the polypeptide chain to exist in seven quasi-equivalent environments: A, B, and C in AB and CC dimers in T = 3 capsids, and A, B, C, and D in AB and CD dimers in T = 4 capsids. We have compared the two capsids by cryo-EM at 3.5 Å resolution. To ensure a valid comparison, the two capsids were prepared and imaged under identical conditions. We find that the chains have different conformations and potential energies, with the T = 3 C chain having the lowest. Three of the four quasi-equivalent dimers are asymmetric with respect to conformation and potential energy; however, the T = 3 CC dimer is symmetrical and has the lowest potential energy although its intra-dimer interface has the least free energy of formation. Of all the inter-dimer interfaces, the CB interface has the least area and free energy, in both capsids. From the calculated energies of higherorder groupings of dimers discernible in the lattices we predict early assembly intermediates, and indeed we observe such structures by negative stain EM of in vitro assembly reactions. By sequence analysis and computational alanine scanning we identify key residues and motifs involved in capsid assembly. Our results explain several previously reported observations on capsid assembly, disassembly, and dimorphism.

show abstract

Section: Introductionmentioning

confidence: 99%

Expression of quasi-equivalence and capsid dimorphism in the Hepadnaviridae

Watts

Cheng

et al. 2020

PLoS Comput Biol

View full text Add to dashboard Cite

show abstract

“…HBV core (HBc) is a small protein, consisting of 183 amino acids produced by ORF C, which is self-assembled to form viral capsids [112][113][114]. The hTid1, a family protein of HSP40, predominantly localizes in mitochondria and is involved in apoptosis [115][116][117].…”

Section: Corementioning

confidence: 99%

Impact of the Interaction of Hepatitis B Virus with Mitochondria and Associated Proteins

Hossain

Akter

Ohsaki

et al. 2020

Viruses

View full text Add to dashboard Cite

Around 350 million people are living with hepatitis B virus (HBV), which can lead to death due to liver cirrhosis and hepatocellular carcinoma (HCC). Various antiviral drugs/nucleot(s)ide analogues are currently used to reduce or arrest the replication of this virus. However, many studies have reported that nucleot(s)ide analogue-resistant HBV is circulating. Cellular signaling pathways could be one of the targets against the viral replication. Several studies reported that viral proteins interacted with mitochondrial proteins and localized in the mitochondria, the powerhouse of the cell. And a recent study showed that mitochondrial turnover induced by thyroid hormones protected hepatocytes from hepatocarcinogenesis mediated by HBV. Strong downregulation of numerous cellular signaling pathways has also been reported to be accompanied by profound mitochondrial alteration, as confirmed by transcriptome profiling of HBV-specific CD8 T cells from chronic and acute HBV patients. In this review, we summarize the ongoing research into mitochondrial proteins and/or signaling involved with HBV proteins, which will continue to provide insight into the relationship between mitochondria and HBV and ultimately lead to advances in viral pathobiology and mitochondria-targeted antiviral therapy.

show abstract

“…This study examined AFA‐mediated cell disruption of P. pastoris (KM71h) with the Covaris E210 series to liberate tandem core Hepatitis B core virus‐like particles (TC‐HBc VLPs) described by Ref. . After screening for significant factors, three AFA experiments were performed to generate response surface models (RSMs) to account for changes in vessel design and enzymatic pretreatment of samples.…”

Section: Introductionmentioning

confidence: 99%

“…This study examined AFA-mediated cell disruption of P. pastoris (KM71h) with the Covaris E210 series to liberate tandem core Hepatitis B core virus-like particles (TC-HBc VLPs) described by Ref 26…”

mentioning

confidence: 99%

Development of a high‐throughput microscale cell disruption platform for Pichia pastoris in rapid bioprocess design

Blaha

Morris

Ogonah

et al. 2017

Biotechnology Progress

View full text Add to dashboard Cite

The time and cost benefits of miniaturized fermentation platforms can only be gained by employing complementary techniques facilitating high-throughput at small sample volumes. Microbial cell disruption is a major bottleneck in experimental throughput and is often restricted to large processing volumes. Moreover, for rigid yeast species, such as Pichia pastoris, no effective high-throughput disruption methods exist. The development of an automated, miniaturized, high-throughput, noncontact, scalable platform based on adaptive focused acoustics (AFA) to disrupt P. pastoris and recover intracellular heterologous protein is described. Augmented modes of AFA were established by investigating vessel designs and a novel enzymatic pretreatment step. Three different modes of AFA were studied and compared to the performance high-pressure homogenization. For each of these modes of cell disruption, response models were developed to account for five different performance criteria. Using multiple responses not only demonstrated that different operating parameters are required for different response optima, with highest product purity requiring suboptimal values for other criteria, but also allowed for AFA-based methods to mimic large-scale homogenization processes. These results demonstrate that AFA-mediated cell disruption can be used for a wide range of applications including buffer development, strain selection, fermentation process development, and whole bioprocess integration. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:130-140, 2018.

show abstract

Assembly Pathway of Hepatitis B Core Virus-like Particles from Genetically Fused Dimers

Cited by 25 publications

References 29 publications

Expression of quasi-equivalence and capsid dimorphism in the Hepadnaviridae

Expression of quasi-equivalence and capsid dimorphism in the Hepadnaviridae

Impact of the Interaction of Hepatitis B Virus with Mitochondria and Associated Proteins

Development of a high‐throughput microscale cell disruption platform for Pichia pastoris in rapid bioprocess design

Contact Info

Product

Resources

About