HHV capsid portal protein

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HHV capsid portal protein
Identifiers
Organism?
SymbolUL6
UniProt P10190

HHV Capsid Portal Protein, or HSV-1 UL-6 protein, is the protein which forms a cylindrical portal in the capsid of Herpes simplex virus (HSV-1). The protein is commonly referred to as the HSV-1 UL-6 protein because it is the transcription product of Herpes gene UL-6.

Contents

The Herpes viral DNA enters and exits the capsid via the capsid portal. The capsid portal is formed by twelve copies of portal protein arranged as a ring; the proteins contain a leucine zipper sequence of amino acids which allow them to adhere to each other. [1] Each icosahedral capsid contains a single portal, located in one vertex. [2] [3]

The portal is formed during initial capsid assembly and interacts with scaffolding proteins that construct the procapsid. [4] [5] [6] When the capsid is nearly complete, the viral DNA enters the capsid (i.e., the DNA is encapsidated) by a mechanism involving the portal and a DNA-binding protein complex similar to bacteriophage terminase. [7] Multiple studies suggest an evolutionary relationship between Capsid Portal Protein and bacteriophage portal proteins. [2] [7]

When a virus infects a cell, it is necessary for the viral DNA to be released from the capsid. The Herpes virus DNA exits through the capsid portal. [8]

The genetic sequence of HSV-1 gene UL-6 is conserved across the family Herpesviridae and this family of genes is known as the "Herpesvirus UL6-like" gene family. [9] "UL-6" is nomenclature meaning that the protein is genetically encoded by the sixth (6th) open reading frame found in the viral genome segment named "Unique-Long (UL)".

Studies

Studies by amino acid sequence location
pUL-6 Amino acid rangeSummaryReference
E121, A618, Q621Point mutations confer resistance to portal assembly inhibitor WAY-150138van Zeijl, et al., 2000 [10]
198-295Deletion mutant forms immature B-capsids with no portalsNellissery, et al., 2007 [3]
322-416Deletion mutants form immature B-capsids which do contain portalsNellissery, et al., 2007 [3]
409-473
L429, L436Mutation studies suggest putative leucine zipper required for portal ring formationNellissery, et al., 2007 [3]
R676Carboxyl (C)-terminal endNCBI Sequence [11]
pUL-26.5 "Scaffolding protein" Amino acid rangeSummaryReference
143-151Deletion inhibits UL-6 portal assemblySinger, et al., 2005 [6]

Dodecameric structure

Research performed in 2004 used electron microscopy to predict that UL-6 forms 11, 12, 13, and 14-unit polymers. The dodecameric form was found to be most likely. [2]

Refinements to the electron microscopy in 2007 allowed finding that the portal is a twelve (12)-unit polymer present at one of the twelve capsid vertices instead of the UL-19 pentamer found at non-portal vertices. [1]

Leucine zipper creates inter-protein adhesion

A study using deletion and mutation of the UL-6 amino acid sequence demonstrated the leucine residues in a predicted leucine zipper motif were required for formation of the dodecameric ring structure. [3]

Early involvement in capsid assembly

Assembly of portal units is an initial step in constructing capsids of viral progeny. Capsids assembled in the absence of portals lack portals. [4]

Interaction with capsid scaffolding protein

In 2003, gel eletrophoresis studies demonstrated that intact UL-6 portals associate in vitro with viral protein UL-26. This association is antagonized by that action of WAY-150138, a thiourea inhibitor of HHV encapsidation. [5]

Further investigation during 2006 showed that assembly of capsid with portal depends on interaction of UL-6 with "scaffolding" protein UL-26.5, amino acids 143 through 151. [6]

Interaction with terminase complex

UL-6 associates with a UL-15/UL-28 protein complex during capsid assembly. The UL-15/UL-28 is believed to bind with viral DNA and serve the same purpose as terminase by packing viral DNA into the capsid during capsid assembly. [7]

Function during DNA egress

The DNA exits the capsid in a single linear segment. DNA exit may be controlled by UL-6 and dependent on temperature or environmental proteins. [8]

Related Research Articles

Capsid

A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The proteins making up the capsid are called capsid proteins or viral coat proteins (VCP). The capsid and inner genome is called the nucleocapsid.

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HHV Latency Associated Transcript is a length of RNA which accumulates in cells hosting long-term, or latent, Human Herpes Virus (HHV) infections. The LAT RNA is produced by genetic transcription from a certain region of the viral DNA. LAT regulates the viral genome and interferes with the normal activities of the infected host cell.

<i>Herpesviridae</i> Family of DNA viruses

Herpesviridae is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein, referring to spreading cutaneous lesions, usually involving blisters, seen in flares of herpes simplex 1, herpes simplex 2 and herpes zoster (shingles). In 1971, the International Committee on the Taxonomy of Viruses (ICTV) established Herpesvirus as a genus with 23 viruses among four groups. Currently, 107 species are recognized, all but one of which are in one of the three subfamilies.

HHV Infected Cell Polypeptide 0

Human Herpes Virus (HHV) Infected Cell Polypeptide 0 (ICP0) is a protein, encoded by the DNA of herpes viruses. It is produced by herpes viruses during the earliest stage of infection, when the virus has recently entered the host cell; this stage is known as the immediate-early or α ("alpha") phase of viral gene expression. During these early stages of infection, ICP0 protein is synthesized and transported to the nucleus of the infected host cell. Here, ICP0 promotes transcription from viral genes, disrupts structures in the nucleus known as nuclear dots or promyelocytic leukemia (PML) nuclear bodies, and alters the expression of host and viral genes in combination with a neuron specific protein. At later stages of cellular infection, ICP0 relocates to the cell cytoplasm to be incorporated into new virion particles.

Herpes simplex virus Species of virus

Herpes simplex virus1 and 2, also known by their taxonomical names Human alphaherpesvirus 1 and Human alphaherpesvirus 2, are two members of the human Herpesviridae family, a set of new viruses that produce viral infections in the majority of humans. Both HSV-1 and HSV-2 are common and contagious. They can be spread when an infected person begins shedding the virus.

Macacine alphaherpesvirus 1, Herpesvirus simiae, or Herpes virus B) is the Simplexvirus infecting macaque monkeys. Macacine alphaherpesvirus 1 is an alphaherpesvirus, which consists of a subset of herpes viruses that travel within hosts using the peripheral nerves. As such, this neurotropic virus is not found in the blood.

CREB3

Cyclic AMP-responsive element-binding protein 3 is a protein that in humans is encoded by the CREB3 gene.

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<i>Herpesvirales</i> Order of viruses

The Herpesvirales is an order of dsDNA viruses with animal hosts, characterised by a common morphology consisting of an icosahedral capsid enclosed in a glycoprotein-containing lipid envelope. Common infections in humans caused by members of this order include cold sores, genital herpes, chickenpox, shingles, and glandular fever. Herpesvirales is the sole order in the class Herviviricetes, which is the sole class in the phylum Peploviricota.

Herpesvirus glycoprotein B

Herpesvirus glycoprotein B is a viral glycoprotein that is involved in the viral cell entry of Herpes simplex virus (HSV). Herpesviruses have an envelope and an outer lipid bilayer which contains twelve surface glycoproteins. For infectivity to be attained, the double stranded DNA genome of HSV must enter the host cell through means of fusion of its envelope with the cellular membrane or via endocytosis. Other viral glycoproteins involved in the process of viral cell entry include gC, gB, gD, gH, and gL, but only gC, gB, gD, and gH are required for the fusion of the HSV's envelope with the cellular membrane. It can be noted that all herpesviruses have glycoproteins gB, gH, and gL.

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Major capsid protein VP1

Major capsid protein VP1 is a viral protein that is the main component of the polyomavirus capsid. VP1 monomers are generally around 350 amino acids long and are capable of self-assembly into an icosahedral structure consisting of 360 VP1 molecules organized into 72 pentamers. VP1 molecules possess a surface binding site that interacts with sialic acids attached to glycans, including some gangliosides, on the surfaces of cells to initiate the process of viral infection. The VP1 protein, along with capsid components VP2 and VP3, is expressed from the "late region" of the circular viral genome.

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Agnoprotein

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Minor capsid protein VP2 and minor capsid protein VP3 are viral proteins that are components of the polyomavirus capsid. Polyomavirus capsids are composed of three proteins; the major component is major capsid protein VP1, which self-assembles into pentamers that in turn self-assemble into enclosed icosahedral structures. The minor components are VP2 and VP3, which bind in the interior of the capsid.

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<i>Duplodnaviria</i> Realm of viruses

Duplodnaviria is a realm of viruses that includes all double-stranded DNA viruses that encode the HK97-fold major capsid protein. The HK97-fold major capsid protein (HK97-MCP) is the primary component of the viral capsid, which stores the viral deoxyribonucleic acid (DNA). Viruses in the realm also share a number of other characteristics, such as an icosahedral capsid, an opening in the viral capsid called a portal, a protease enzyme that empties the inside of the capsid prior to DNA packaging, and a terminase enzyme that packages viral DNA into the capsid.

References

  1. 1 2 Cardone G, Winkler DC, Trus BL, Cheng N, Heuser JE, Newcomb WW, Brown JC, Steven AC (2007-05-10). "Visualization of the herpes simplex virus portal in situ by cryo-electron tomography". Virology. 361 (2): 426–34. doi:10.1016/j.virol.2006.10.047. PMC   1930166 . PMID   17188319.
  2. 1 2 3 Trus BL, Cheng N, Newcomb WW, Homa FL, Brown JC, Steven AC (November 2004). "Structure and polymorphism of the UL6 portal protein of herpes simplex virus type 1". Journal of Virology. 78 (22): 12668–71. doi:10.1128/JVI.78.22.12668-12671.2004. PMC   525097 . PMID   15507654.(Article: )
  3. 1 2 3 4 5 Nellissery JK, Szczepaniak R, Lamberti C, Weller SK (2007-06-20). "A putative leucine zipper within the HSV-1 UL6 protein is required for portal ring formation". Journal of Virology. 81 (17): 8868–77. doi:10.1128/JVI.00739-07. PMC   1951442 . PMID   17581990.
  4. 1 2 Newcomb WW, Homa FL, Brown JC (August 2005). "Involvement of the portal at an early step in herpes simplex virus capsid assembly". Journal of Virology. 79 (16): 10540–6. doi:10.1128/JVI.79.16.10540-10546.2005. PMC   1182615 . PMID   16051846.
  5. 1 2 Newcomb WW, Thomsen DR, Homa FL, Brown JC (September 2003). "Assembly of the herpes simplex virus capsid: identification of soluble scaffold-portal complexes and their role in formation of portal-containing capsids". Journal of Virology. 77 (18): 9862–71. doi:10.1128/JVI.77.18.9862-9871.2003. PMC   224603 . PMID   12941896. (Article: )
  6. 1 2 3 Singer GP, Newcomb WW, Thomsen DR, Homa FL, Brown JC (2005). "Identification of a region in the herpes simplex virus scaffolding protein required for interaction with the portal". Journal of Virology. 79 (1): 132–9. doi:10.1128/JVI.79.1.132-139.2005. PMC   538710 . PMID   15596809.
  7. 1 2 3 White CA, Stow ND, Patel AH, Hughes M, Preston VG (June 2003). "Herpes Simplex Virus Type 1 Portal Protein UL6 Interacts with the Putative Terminase Subunits UL15 and UL28". Journal of Virology. 77 (11): 6351–8. doi:10.1128/JVI.77.11.6351-6358.2003. PMC   154995 . PMID   12743292.
  8. 1 2 Newcomb WW, Booy FP, Brown JC (2007-05-13). "Uncoating the Herpes Simplex Virus Genome". Journal of Molecular Biology. 370 (4): 633–42. doi:10.1016/j.jmb.2007.05.023. PMC   1975772 . PMID   17540405.
  9. ↑ Herpesvirus UL6 like Conserved Domains view at NCBI
  10. ↑ Marja van Zeijl; Jeanette Fairhurst; Thomas R. Jones; Steven K. Vernon; John Morin; James LaRocque; Boris Feld; Bryan O'Hara; Jonathan D. Bloom; Stephen V. Johann (October 2000). "Novel Class of Thiourea Compounds That Inhibit Herpes Simplex Virus Type 1 DNA Cleavage and Encapsidation: Resistance Maps to the UL6 Gene". Journal of Virology. 74 (19): 9054–9061. doi:10.1128/JVI.74.19.9054-9061.2000. PMC   102102 . PMID   10982350.
  11. ↑ HSV-1 UL-6 amino acid sequence at NCBI
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