Disease relevance of UL6

• Residues 150-183 are known to form a protamine-like domain required for packaging RNA, and residues 1-149 form the 'assembly domain' that polymerizes into capsids and, unusually for a capsid protein, is highly alpha-helical [1].
• The virion consists of a lipoprotein envelope surrounding an icosahedral capsid composed of dimers of a 183-residue protein, 'core antigen' (HBcAg) [1].
• Arrangement of the UL6 to UL20 homologues of ILTV is almost identical to that found in the herpes simplex virus type 1 genome [2].
• During this time, antibodies to EBV-associated viral capsid antigens and early antigens of D and R specificity, as well as antibodies against herpes simplex, varicella, cytomegalovirus, measles, and respiratory syncytial virus antigens, did not show any consistent or impressive changes [3].
• A model for the hepatitis B virus core protein: prediction of antigenic sites and relationship to RNA virus capsid proteins [4].

High impact information on UL6

• Large core gene deletions showed no capsid formation and HBV replication, which resulted in nuclear core expression [5].
• This assay is adaptable to high-throughput screening and can identify small-molecule inhibitors of virus assembly that prevent, inappropriately accelerate and/or misdirect capsid formation to yield aberrant particles [6].
• Because the replication of hepatitis B virus (HBV) proceeds via an obligatory reverse transcription step in the viral capsid, cDNA is potentially vulnerable to editing by cytidine deaminases of the APOBEC3 family [7].
• Here, we examine the effect of a representative HAP molecule, methyl 4-(2-chloro-4-fluorophenyl)-6-methyl-2-(pyridin-2-yl)-1,4-dihydropyrimidine-5-carboxylate (HAP-1), on the in vitro assembly of HBV capsid protein (Cp) [8].
• Dynamics of herpes simplex virus capsid maturation visualized by time-lapse cryo-electron microscopy [9].

Chemical compound and disease context of UL6

• Central role of a serine phosphorylation site within duck hepatitis B virus core protein for capsid trafficking and genome release [10].
• We conclude that Cys residues and disulfides are not required for the assembly of either HBV capsids or the dimers that provide the precursors for capsid assembly [11].
• Tumor necrosis factor alpha inhibition of hepatitis B virus replication involves disruption of capsid Integrity through activation of NF-kappaB [12].
• Structure of the herpes simplex virus capsid: effects of extraction with guanidine hydrochloride and partial reconstitution of extracted capsids [13].
• We found previously that three serines and one threonine in the C-terminal 24 amino acids of the capsid protein serve as phosphorylation sites and that the pattern of phosphorylation at these sites in intracellular viral capsids is complex [14].

Biological context of UL6

• The exposure of the NLS is regulated and depends upon genome maturation and/or phosphorylation of the capsid protein [15].
• Virus-derived capsids that contained the mature viral genome were able to release the viral DNA and capsid protein into the nucleoplasm [16].
• Envelopment must not happen before reverse transcription is completed, so it has been hypothesized that a change in capsid structure may signal maturation [17].
• Inhibition of viral DNA replication resulted in decreased synthesis and transport of the capsid protein [18].
• We have demonstrated that the DNA binding protein and the capsid protein exchange from the cytoplasmic framework to the nuclear framework, suggesting the direct movement of the proteins from one structure to the other [18].

Anatomical context of UL6

• The intracytosolic translocation is facilitated by the viral capsid that surrounds the genome and that interacts with cellular microtubules [15].
• Recombinant capsid-like core particles are used as effective carriers of foreign T and B cell epitopes and as delivery vehicles for oligonucleotides [19].
• Soluble heparin and heparan sulfate but not chondroitin sulfates greatly diminished cytokine induction through inhibition of capsid binding to THP-1 macrophages [20].
• Injected oocytes produce both a nonparticulate p21.5 species (free p21.5) and capsid particles [21].
• No capsid structures were observed by electron microscopic analysis of thin sections of K5 delta Z- and K23Z-infected Vero cells [22].

Associations of UL6 with chemical compounds

• BAY41-4109 inhibits virus production in vivo by a mechanism that targets the viral capsid [23].
• A negative ionic charge as contributed by phosphorylated serine or aspartic acid-supported nuclear localization of the viral capsid and generation of nuclear superhelical DNA [10].
• Electron microscopic direct visualization of the nucleoprotein complexes after sucrose or metrizamide purification revealed that the proteins were preferentially associated with one end of the DNA molecule and formed large irregular terminal thickenings or capsid-like transparent shells enclosing polyglobular cores [24].
• Mutation of the downstream proline to glycine at each site had the same effect as mutating the serine itself, suggesting an SP or TP motif as an essential feature for capsid protein phosphorylation [25].
• Fractionation of radiolabeled oocyte extracts on 10 to 60% sucrose gradients revealed that Cys-minus core proteins resolved into the nonparticulate and capsid forms seen for wild-type p21 [11].

Analytical, diagnostic and therapeutic context of UL6

• The capsid is assembled from dimers via interactions involving a highly conserved region near the C terminus of the truncated protein used for crystallization [26].
• These observations suggest an explanation for the distinction between cAg and e-antigen (an unassembled form of capsid protein) and an approach to immunodiagnosis, exploiting the diversity of cAg epitopes [27].
• HBV may therefore be particularly vulnerable to the capsid-targeted viral inactivation approach [28].
• Capsids and capsid-related structures formed during progressively longer periods of incubation were examined by electron microscopy of thin-sectioned specimens [29].
• Bis-ANS inhibited in vitro capsid assembly induced by ionic strength as observed by light scattering and size exclusion chromatography [30].

References