scholarly journals The Ins and Outs of Herpesviral Capsids: Divergent Structures and Assembly Mechanisms across the Three Subfamilies

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1913
Author(s):  
Elizabeth B. Draganova ◽  
Jonathan Valentin ◽  
Ekaterina E. Heldwein
Keyword(s):  
Capsid Protein ◽  
Severe Disease ◽  
Human Herpesvirus ◽  
Dna Viruses ◽  
Double Stranded Dna ◽  
Cryo Electron Microscopy ◽  
Protein Functions ◽  
Attractive Therapeutic Target ◽  
Key Steps ◽  
Human Herpesviruses

Human herpesviruses, classified into three subfamilies, are double-stranded DNA viruses that establish lifelong latent infections within most of the world’s population and can cause severe disease, especially in immunocompromised people. There is no cure, and current preventative and therapeutic options are limited. Therefore, understanding the biology of these viruses is essential for finding new ways to stop them. Capsids play a central role in herpesvirus biology. They are sophisticated vehicles that shelter the pressurized double-stranded-DNA genomes while ensuring their delivery to defined cellular destinations on the way in and out of the host cell. Moreover, the importance of capsids for multiple key steps in the replication cycle makes their assembly an attractive therapeutic target. Recent cryo-electron microscopy reconstructions of capsids from all three subfamilies of human herpesviruses revealed not only conserved features but also remarkable structural differences. Furthermore, capsid assembly studies have suggested subfamily-specific roles of viral capsid protein homologs. In this review, we compare capsid structures, assembly mechanisms, and capsid protein functions across human herpesvirus subfamilies, highlighting the differences.

scholarly journals Impacts of Genome-Wide Analyses on Our Understanding of Human Herpesvirus Diversity and Evolution

2017 ◽  
Vol 92 (1) ◽  
Author(s):  
Daniel W. Renner ◽  
Moriah L. Szpara
Keyword(s):  
High Throughput Sequencing ◽  
Evolutionary Dynamics ◽  
Human Herpesvirus ◽  
Ribosome Profiling ◽  
Genomic Diversity ◽  
Rna Seq ◽  
Dna Viruses ◽  
Double Stranded Dna ◽  
Genome Wide ◽  
Human Herpesviruses

ABSTRACTUntil fairly recently, genome-wide evolutionary dynamics and within-host diversity were more commonly examined in the context of small viruses than in the context of large double-stranded DNA viruses such as herpesviruses. The high mutation rates and more compact genomes of RNA viruses have inspired the investigation of population dynamics for these species, and recent data now suggest that herpesviruses might also be considered candidates for population modeling. High-throughput sequencing (HTS) and bioinformatics have expanded our understanding of herpesviruses through genome-wide comparisons of sequence diversity, recombination, allele frequency, and selective pressures. Here we discuss recent data on the mechanisms that generate herpesvirus genomic diversity and underlie the evolution of these virus families. We focus on human herpesviruses, with key insights drawn from veterinary herpesviruses and other large DNA virus families. We consider the impacts of cell culture on herpesvirus genomes and how to accurately describe the viral populations under study. The need for a strong foundation of high-quality genomes is also discussed, since it underlies all secondary genomic analyses such as RNA sequencing (RNA-Seq), chromatin immunoprecipitation, and ribosome profiling. Areas where we foresee future progress, such as the linking of viral genetic differences to phenotypic or clinical outcomes, are highlighted as well.

scholarly journals Structure of faustovirus, a large dsDNA virus

2016 ◽  
Vol 113 (22) ◽  
pp. 6206-6211 ◽  
Author(s):  
Thomas Klose ◽  
Dorine G. Reteno ◽  
Samia Benamar ◽  
Adam Hollerbach ◽  
Philippe Colson ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Major Capsid Protein ◽  
Dsdna Virus ◽  
Dna Virus ◽  
Dna Viruses ◽  
Double Stranded Dna ◽  
Cryo Electron Microscopy ◽  
Maturation Stages ◽  
Jelly Roll ◽  
Protein Shell

Many viruses protect their genome with a combination of a protein shell with or without a membrane layer. Here we describe the structure of faustovirus, the first DNA virus (to our knowledge) that has been found to use two protein shells to encapsidate and protect its genome. The crystal structure of the major capsid protein, in combination with cryo-electron microscopy structures of two different maturation stages of the virus, shows that the outer virus shell is composed of a double jelly-roll protein that can be found in many double-stranded DNA viruses. The structure of the repeating hexameric unit of the inner shell is different from all other known capsid proteins. In addition to the unique architecture, the region of the genome that encodes the major capsid protein stretches over 17,000 bp and contains a large number of introns and exons. This complexity might help the virus to rapidly adapt to new environments or hosts.

Cryo-EM structure of a herpesvirus capsid at 3.1 Å

Science ◽  
2018 ◽  
Vol 360 (6384) ◽  
pp. eaao7283 ◽  
Author(s):  
Shuai Yuan ◽  
Jialing Wang ◽  
Dongjie Zhu ◽  
Nan Wang ◽  
Qiang Gao ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Disulfide Bonds ◽  
Major Capsid Protein ◽  
Noncovalent Interactions ◽  
Cryo Electron Microscopy ◽  
Reconstruction Strategy ◽  
Simplex Virus ◽  
Capsid Stability ◽  
Human Herpesviruses

Structurally and genetically, human herpesviruses are among the largest and most complex of viruses. Using cryo–electron microscopy (cryo-EM) with an optimized image reconstruction strategy, we report the herpes simplex virus type 2 (HSV-2) capsid structure at 3.1 angstroms, which is built up of about 3000 proteins organized into three types of hexons (central, peripentonal, and edge), pentons, and triplexes. Both hexons and pentons contain the major capsid protein, VP5; hexons also contain a small capsid protein, VP26; and triplexes comprise VP23 and VP19C. Acting as core organizers, VP5 proteins form extensive intermolecular networks, involving multiple disulfide bonds (about 1500 in total) and noncovalent interactions, with VP26 proteins and triplexes that underpin capsid stability and assembly. Conformational adaptations of these proteins induced by their microenvironments lead to 46 different conformers that assemble into a massive quasisymmetric shell, exemplifying the structural and functional complexity of HSV.

scholarly journals Diversity and Abundance of Single-Stranded DNA Viruses in Human Feces

2011 ◽  
Vol 77 (22) ◽  
pp. 8062-8070 ◽  
Author(s):  
Min-Soo Kim ◽  
Eun-Jin Park ◽  
Seong Woon Roh ◽  
Jin-Woo Bae
Keyword(s):  
Capsid Protein ◽  
Protein Sequences ◽  
Single Stranded Dna ◽  
Dna Viruses ◽  
Content Type ◽  
Double Stranded Dna ◽  
Abundance And Diversity ◽  
Ssdna Viruses ◽  
Virus Abundance ◽  
Large Contigs

ABSTRACTIn this study, we investigated the abundance and diversity of single-stranded DNA (ssDNA) viruses in fecal samples from five healthy individuals through a combination of serial filtration and CsCl gradient ultracentrifugation. Virus abundance ranged from 108to 109per gram of feces, and virus-to-bacterium ratios were much lower (less than 0.1) than those observed in aquatic environments (5 to 10). Viral DNA was extracted and randomly amplified using phi29 polymerase and analyzed through high-throughput 454 pyrosequencing. Among 400,133 sequences, an average of 86.2% viromes were previously uncharacterized in public databases. Among previously known viruses, double-stranded DNA podophages (52 to 74%), siphophages (11 to 30%), myophages (1 to 4%), and ssDNA microphages (3 to 9%) were major constituents of human fecal viromes. A phylogenetic analysis of 24 large contigs of microphages based on conserved capsid protein sequences revealed five distinct newly discovered evolutionary microphage groups that were distantly related to previously known microphages. Moreover, putative capsid protein sequences of five contigs were closely related to prophage-like sequences in the genomes of threeBacteroidesand threePrevotellastrains, suggesting thatBacteroidesandPrevotellaare the sources of infecting microphages in their hosts.

scholarly journals Cryo-EM analysis of a viral portal protein in situ reveals a switch in the DNA tunnel

2019 ◽  
Author(s):  
Oliver W. Bayfield ◽  
Alasdair C. Steven ◽  
Alfred A. Antson
Keyword(s):  
Surface Properties ◽  
Dynamic Processes ◽  
Viral Capsid ◽  
Capsid Assembly ◽  
Genome Packaging ◽  
Dna Viruses ◽  
Portal Protein ◽  
Double Stranded Dna ◽  
Protein Functions

The portal protein is a key component of many double-stranded DNA viruses, governing capsid assembly and genome packaging. Twelve subunits of the portal protein form a ring with a central tunnel, through which DNA is translocated into the capsid. It is unknown how the portal protein functions as a gatekeeper, preventing DNA slippage, whilst allowing its passage into the capsid through its central tunnel, and how these processes can be controlled by capsid and motor proteins. A cryo-EM structure of a portal protein, determined in situ for immature capsids of thermostable bacteriophage P23-45, suggests how domain adjustments can be coupled with a switching of properties of the DNA tunnel. Of particular note is an inversion of the conformation of portal loops which define the tunnel’s constriction, accompanied by a switching of surface properties from hydrophobic to hydrophilic. These observations indicate how translocation of DNA into the viral capsid can be modulated by changes in the properties and size of the central tunnel and how the changing pattern of protein–capsid interactions across a symmetry-mismatched interface can facilitate these dynamic processes.

scholarly journals Cryo-EM structure in situ reveals a molecular switch that safeguards virus against genome loss

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Oliver W Bayfield ◽  
Alasdair C Steven ◽  
Alfred A Antson
Keyword(s):  
Protein Interactions ◽  
Bound State ◽  
Molecular Switch ◽  
Protein Protein Interactions ◽  
Genome Packaging ◽  
Dna Viruses ◽  
Portal Protein ◽  
Double Stranded Dna ◽  
Protein Functions

The portal protein is a key component of many double-stranded DNA viruses, governing capsid assembly and genome packaging. Twelve subunits of the portal protein define a tunnel, through which DNA is translocated into the capsid. It is unknown how the portal protein functions as a gatekeeper, preventing DNA slippage, whilst allowing its passage into the capsid, and how these processes are controlled. A cryo-EM structure of the portal protein of thermostable virus P23-45, determined in situ in its procapsid-bound state, indicates a mechanism that naturally safeguards the virus against genome loss. This occurs via an inversion of the conformation of the loops that define the constriction in the central tunnel, accompanied by a hydrophilic–hydrophobic switch. The structure also shows how translocation of DNA into the capsid could be modulated by a changing mode of protein–protein interactions between portal and capsid, across a symmetry-mismatched interface.

Enzymes of Human Herpesviruses

1992 ◽  
Vol 57 (8) ◽  
pp. 1577-1612 ◽  
Author(s):  
Pavel Kramata ◽  
Ivan Votruba
Keyword(s):  
Binding Protein ◽  
Human Herpesvirus ◽  
Dna Helicase ◽  
Point Of View ◽  
Uracil Dna Glycosylase ◽  
Replication Complex ◽  
Viral Genomes ◽  
Origin Binding Protein ◽  
Antiviral Chemotherapy ◽  
Human Herpesviruses

The properties of human herpesvirus-encoded enzymes are reviewed and the importance of sequence analysis of viral genomes as well as the experiments on characteristics of enzymes isolated from infected cell cultures are emphasized. The following enzymes are described in detail: DNA replication complex consisting of DNA polymerase, DNA helicase-primase, single-stranded DNA binding protein and origin binding protein, further thymidine kinase, ribonucleotide reductase, deoxyuridine triphosphatase as well as uracil-DNA-glycosylase, deoxyribonuclease and protein kinase. The importance of these enzymes from the point of view of antiviral chemotherapy is discussed.

scholarly journals Structural Analysis of Jumbo Coliphage phAPEC6

2020 ◽  
Vol 21 (9) ◽  
pp. 3119 ◽  
Author(s):  
Jeroen Wagemans ◽  
Jessica Tsonos ◽  
Dominique Holtappels ◽  
Kiandro Fortuna ◽  
Jean-Pierre Hernalsteens ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Capsid Protein ◽  
Tem Analysis ◽  
Host Interaction ◽  
Cryo Electron Microscopy ◽  
Transmission Electron ◽  
Tail Sheath ◽  
Associated Proteins ◽  
Contractile Tail ◽  
Phage Capsid

The phAPEC6 genome encodes 551 predicted gene products, with the vast majority (83%) of unknown function. Of these, 62 have been identified as virion-associated proteins by mass spectrometry (ESI-MS/MS), including the major capsid protein (Gp225; present in 1620 copies), which shows a HK97 capsid protein-based fold. Cryo-electron microscopy experiments showed that the 350-kbp DNA molecule of Escherichia coli virus phAPEC6 is packaged in at least 15 concentric layers in the phage capsid. A capsid inner body rod is also present, measuring about 91 nm by 18 nm and oriented along the portal axis. In the phAPEC6 contractile tail, 25 hexameric stacked rings can be distinguished, built of the identified tail sheath protein (Gp277). Cryo-EM reconstruction reveals the base of the unique hairy fibers observed during an initial transmission electron microscopy (TEM) analysis. These very unusual filaments are ordered at three annular positions along the contractile sheath, as well as around the capsid, and may be involved in host interaction.

scholarly journals Human Herpesvirus and the Immune Checkpoint PD-1/PD-L1 Pathway: Disorders and Strategies for Survival

2021 ◽  
Vol 9 (4) ◽  
pp. 778
Author(s):  
Takayuki Murata
Keyword(s):  
Cell Death ◽  
Immune System ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Human Herpesvirus ◽  
Barr Virus ◽  
Programmed Cell Death 1 ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Human Herpesviruses

The immune system has evolved as a complex and efficient means of coping with extrinsic materials, such as pathogens and toxins, as well as intrinsic abnormalities, such as cancers. Although rapid and timely activation of the immune system is obviously important, regulated downregulation of the system is almost as significant as activation to prevent runaway immunity, such as allergies and hypercytokinemia. Therefore, the immune checkpoint programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is beneficial for the host. On the other hand, pathogens have evolved to evade host immunity by taking advantage of the PD-1/PD-L1 pathway. This review is focused on human herpesviruses, such as herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein–Barr virus (EBV), which cause various types of disorders, and their relationships with the PD-1/PD-L1 pathway. Understanding such relationships will be useful for developing preventative and therapeutic methods for disorders caused by herpesviruses.

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