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A kind of typical metal-organic frameworks (MOFs) material, HKUST-1 was prepared by hydrothermal method and characterized by XRD and SEM. The results of characterizations manifested that HKUST-1 showed a regular octahedral crystal structure. The as-prepared HKUST-1 was modified by several kinds of organic base materials and the 2 adsorption behaviors of modified HKUST-1 materials were evaluated. The 2 adsorption capacities of different base modified HKUST-1 varied with the base intensity of modified organic base materials. [ABSTRACT FROM AUTHOR]

Human herpesvirus-6B (HHV-6B) is a T lymphotropic β-herpesvirus that is clearly distinct from human herpesvirus-6A (HHV-6A) according to molecular biological features. The International Committee on Taxonomy of Viruses recently classified HHV-6B as a separate species. The primary HHV-6B infection causes exanthem subitum and is sometimes associated with severe encephalopathy. More than 90% of the general population is infected with HHV-6B during childhood, and the virus remains throughout life as a latent infection. HHV-6B reactivation causes encephalitis in immunosuppressed patients. The cellular receptor for HHV-6A entry was identified as human CD46, but the receptor for HHV-6B has not been clear. Here we found that CD134, a member of the TNF receptor superfamily, functions as a specific entry receptor for HHV-6B. A T-cell line that is normally nonpermissive for HHV-6B infection became highly susceptible to infection when CD134 was overexpressed. CD134 was down-regulated in HHV-6B-infected T cells. Soluble CD134 interacted with the HHV-6B glycoprotein complex that serves as a viral ligand for cellular receptor, which inhibited HHV-6B but not HHV-6A infection in target cells. The identification of CD134 as an HHV-6B specific entry receptor provides important insight into understanding HHV-6B entry and its pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Human herpesvirus 6 (HHV-6) glycoprotein Q1 (gQ1), a unique gene in HHV-6, forms a complex with glycoproteinH (gH) and gL, which is the viral ligand for its cellular receptor, CD46. However, whether gQ1 is essential for virus growth is unknown, because a system is lacking for making gene knockouts for HHV-6. Recently, bacterial artificial chromosome (BAC) and E. coli mutagenesis techniques have been applied to herpesvirus investigation. Here we successfully inserted the HHV-6A genome into a BAC, and obtained reconstituted infectious virus from the HHV-6A-containing BAC DNA. Using this system, we generated a gQ1 mutant virus genome, which failed to yield reconstituted infectious virus, whereas its revertant virus could be produced, indicating that the HHV-6 gQ1 gene is essential for virus growth. Therefore, we successfully applied BAC and E. coli mutagenesis techniques to the study of HHV-6, and discovered that HHV-6 gQ1 is an essential gene for virus growth. [ABSTRACT FROM AUTHOR]

Abstract: Cell-membrane raft microdomains are important for successful infection by several viruses. However, their role in the cell-entry process of human herpesvirus-6 (HHV-6) is unknown. Here we tested whether HHV-6 requires cell-membrane rafts for its entry. When cell-membrane rafts were disrupted by cholesterol depletion, target-cell entry by HHV-6 was inhibited, although the virus bound normally to the cells. HHV-6 infectivity was partially rescued by adding exogenous cholesterol. Interestingly, the HHV-6 cellular receptor, CD46, was found in the rafts after virus attachment, but not in the rafts of uninfected cells, indicating that HHV-6 infection induces the re-location of its receptor into the rafts. Furthermore, glycoprotein Q1, part of a viral glycoprotein complex that binds CD46, was also associated with rafts immediately after infection. These data suggest that cellular-membrane lipid rafts are important in viral entry and that HHV-6 may enter the target cells via the rafts. [Copyright &y& Elsevier]

The tegument protein U14 of human herpesvirus 6B (HHV-6B) constitutes the viral virion structure and is essential for viral growth. To define the characteristics and functions of U14, we determined the crystal structure of the N-terminal domain of HHV-6B U14 (U14-NTD) at 1.85 Å resolution. U14-NTD forms an elongated helix-rich fold with a protruding β hairpin. U14-NTD exists as a dimer exhibiting broad electrostatic interactions and a network of hydrogen bonds. This is first report of the crystal structure and dimerization of HHV-6B U14. The surface of the U14-NTD dimer reveals multiple clusters of negatively- and positively-charged residues that coincide with potential functional sites of U14. Three successive residues, L424, E425 and V426, which relate to viral growth, reside on the β hairpin close to the dimer's two-fold axis. The hydrophobic side-chains of L424 and V426 that constitute a part of a hydrophobic patch are solvent-exposed, indicating the possibility that the β hairpin region is a key functional site of HHV-6 U14. Structure-based sequence comparison suggests that U14-NTD corresponds to the core fold conserved among U14 homologs, human herpesvirus 7 U14, and human cytomegalovirus UL25 and UL35, although dimerization appears to be a specific feature of the U14 group. [ABSTRACT FROM AUTHOR]

All herpesviruses contain a tegument layer comprising a protein matrix; these proteins play key roles during viral assembly and egress. Here, liquid chromatography and tandem mass spectrometry analysis (LC–MS/MS) of proteins from human herpesvirus 6 (HHV-6)-infected cells revealed a possible association between two major tegument proteins, U14 and U11. This association was verified by immunoprecipitation experiments. Moreover, U11 protein was expressed during the late phase of infection and incorporated into virions. Finally, in contrast to its revertant, a U11 deletion mutant could not be reconstituted. Taken together, these results suggest that HHV-6 U11 is an essential gene for virus growth and propagation. [ABSTRACT FROM AUTHOR]

The human herpesvirus-6 (HHV-6) infection induces cell-cycle arrest. In this study, we found that the HHV-6-encoded U14 protein induced cell-cycle arrest at G2/M phase via an association with the cellular protein EDD, a mediator of DNA-damage signal transduction. In the early phase of HHV-6 infection, U14 colocalized with EDD dots in the nucleus, and similar colocalization was also observed in cells transfected with a U14 expression vector. When the carboxyl-terminal region of U14 was deleted, no association of U14 and EDD was observed, and the percentage of cells in G2/M decreased relative to that in cells expressing wild-type U14, indicating that the C-terminal region of U14 and the U14–EDD association are critical for the cell-cycle arrest induced by U14. These results indicate that U14 is a G2/M checkpoint regulator encoded by HHV-6. [ABSTRACT FROM AUTHOR]

Abstract: Human herpesvirus 6 (HHV-6), which replicates abundantly in T cells, belongs to the Roseolovirus genus within the betaherpesvirus subfamily. Members of the Roseolovirus genus encode seven unique genes, U20, U21, U23, U24, U24A, U26, and U100. The present study focused on one of these, U23, by analyzing the characteristics of its gene product in HHV-6A-infected cells. The results indicated that the U23 protein was expressed at the late phase of infection as a glycoprotein, but was not incorporated into virions, and mostly stayed within the trans Golgi network (TGN) in HHV-6A-infected cells. Furthermore, analysis using a U23-defective mutant virus showed that the gene is nonessential for viral replication in vitro. [Copyright &y& Elsevier]

A unique glycoprotein is expressed on the virus envelope of human herpesvirus 6B (HHV-6B): the complex gH/gL/gQ1/gQ2 (hereafter referred to as the HHV-6B tetramer). This tetramer recognizes a host receptor expressed on activated T cells: human CD134 (hCD134). This interaction is essential for HHV-6B entry into the susceptible cells and is a determinant for HHV-6B cell tropism. The structural mechanisms underlying this unique interaction were unknown. Herein we solved the interactions between the HHV-6B tetramer and the receptor by using their neutralizing antibodies in molecular and structural analyses. A surface plasmon resonance analysis revealed fast dissociation/association between the tetramer and hCD134, although the affinity was high (KD = 18 nM) and comparable to those for the neutralizing antibodies (anti-gQ1: 17 nM, anti-gH: 2.7 nM). A competition assay demonstrated that the anti-gQ1 antibody competed with hCD134 in the HHV-6B tetramer binding whereas the anti-gH antibody did not, indicating the direct interaction of gQ1 and hCD134. A single-particle analysis by negative-staining electron microscopy revealed the tetramer's elongated shape with a gH/gL part and extra density corresponding to gQ1/gQ2. The anti-gQ1 antibody bound to the tip of the extra density, and anti-gH antibody bound to the putative gH/gL part. These results highlight the interaction of gQ1/gQ2 in the HHV-6B tetramer with hCD134, and they demonstrate common features among viral ligands of the betaherpesvirus subfamily from a macroscopic viewpoint. Author summary: Primary infection of human herpesvirus 6B (HHV-6B) with fever and roseola occurs for almost all children, and HHV-6B remains in the host as a latent infection. The reactivation of HHV-6B (especially in patients after hematopoietic stem-cell transplantation) occasionally causes severe encephalitis, which is a public health concern worldwide. HHV-6B's unique gH/gL/gQ1/gQ2 complex (a tetramer expressed on the viral envelope) recognizes the cellular receptor, i.e., human CD134 (hCD134), which is essential for the entry of the virus into the host's cells. The interaction between HHV-6B tetramer and hCD134 is therefore one of the determinants of HHV-6B-specific cell tropism. This article sheds light on the molecular and structural interactions between HHV-6B tetramer and its host receptor along with their neutralizing antibodies, and their affinities, competition, and binding modes based on the HHV-6B tetramer structure are described. Our findings provide molecular and structural bases for a comprehensive understanding of these interactions and relationships. [ABSTRACT FROM AUTHOR]

Human herpesvirus 6 (HHV-6) is an important immunosuppressive and immunomodulatory virus worldwide. However, whether and how HHV-6 infection influences the metabolic machinery of the host cell to provide the energy and biosynthetic resources for virus propagation remains unknown. In this study, we identified that HHV-6A infection promotes glucose metabolism in infected T cells, resulting in elevated glycolytic activity with an increase of glucose uptake, glucose consumption and lactate secretion. Furthermore, we explored the mechanisms involved in HHV-6A-mediated glycolytic activation in the infected T cells. We found increased expressions of the key glucose transporters and glycolytic enzymes in HHV-6A-infected T cells. In addition, HHV-6A infection dramatically activated AKT-mTORC1 signaling in the infected T cells and pharmacological inhibition of mTORC1 blocked HHV-6A-mediated glycolytic activation. We also found that direct inhibition of glycolysis by 2-Deoxy-D-glucose (2-DG) or inhibition of mTORC1 activity in HHV-6A-infected T cells effectively reduced HHV-6 DNA replication, protein synthesis and virion production. These results not only reveal the mechanism of how HHV-6 infection affects host cell metabolism, but also suggest that targeting the metabolic pathway could be a new avenue for HHV-6 therapy. Author summary: Human herpesvirus 6 (HHV-6) is a member of the betaherpesvirinae family, which primarily infects T lymphocytes. In the study presented here, we have demonstrated that HHV-6A infection promotes glucose metabolism in infected T cells. Further exploration into the mechanism demonstrated that HHV-6A infection increases the expressions of the key glucose transporters and glycolytic enzymes, as well as activates the AKT-mTORC1 signaling, which is involved in HHV-6A-induced glycolysis activation in HHV-6-infected T cells. Importantly, suppression of glycolysis or mTORC1 activity effectively reduced HHV-6A propagation. Therefore, recognition of the effects of HHV-6 on host cell metabolism will not only facilitate a better understanding of viral pathogenesis but also could reveal potential therapeutic targets for HHV-6-associated diseases by metabolic manipulation. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) refers to external force-induced brain damage, characterized with necrosis and cell loss in cerebral cortex. Interestingly, a plant-extract named formononetin (FN) is found to possess promising pharmacological activities, including cellular neuroprotection. Thus, we propose that FN may exert biological protection against TBI and discuss the underlying mechanism. In the current study, a rat TBI model was established via Feeney's classical method, followed by different concentrations of FN treatment. Nissl-special and DAPI-labeled stains were utilized to assess the proliferation of cortical neurons nearing lesioned tissue. The contents of interleukin-6 (IL6), tumor necrosis factor (TNF-α), and interleukin-10 (IL10) in serum and the cortical neurons were determined by ELISA. Further, intracephalic IL10 expression levels were detected through immunoassay and RT-PCR. Interestingly, the results exhibited within the FN-treated TBI rat model indicated elevated cortical proliferation. The levels of IL10 in serum and the cortical neurons were increased following FN treatments, while TNF-α and IL6 levels in the blood were decreased. In addition, both mRNA and protein expression levels of IL10 in the FN-treated TBI rat model were up-regulated in a dose-dependent manner. Collectively, our present findings indicate that FN provides effective neuroprotection against TBI, likely by activating IL10 expression in cortical neurons nearing lesioned tissue to inhibit neuroinflammatory reaction. [ABSTRACT FROM AUTHOR]

Human herpesvirus 6 (HHV-6) glycoprotein B (gB) is an abundantly expressed viral glycoprotein required for viral entry and cell fusion, and is highly conserved among herpesviruses. The present study examined the function of HHV-6 gB cytoplasmic tail domain (CTD). A gB CTD deletion mutant was constructed which, in contrast to its revertant, could not be reconstituted. Moreover, deletion of gB cytoplasmic tail impaired the intracellular transport of gB protein to the trans -Golgi network (TGN). Taken together, these results suggest that gB CTD is critical for HHV-6 propagation and important for intracellular transportation. [ABSTRACT FROM AUTHOR]

Human herpesvirus 6 is a T lymphotropic herpesvirus, long classified into variants A and B (HHV-6A and HHV-6B) based on differences in sequence and pathogenicity. Recently, however, HHV-6A and HHV-6B were reclassified as different species. Here, we isolated a neutralizing monoclonal antibody (Mab) named AgQ 1-1 that was specific for HHV-6A glycoprotein Q1 (AgQl), and we showed that amino acid residues 494 to 497 of AgQl were critical for its recognition by this Mab. This region was also essential for AgQl's complex formation with gH, gL, and gQ2, which might be important for viral binding to the cellular receptor, CD46. In addition, amino acid residues 494 to 497 are essential for viral replication. Interestingly, this sequence corresponds to the domain on HHV-6B gQl that is critical for recognition by an HHV-6B-specific neutralizing Mab. Within this domain, only Q at position 496 of HHV-6A is distinct from the HHV-6B sequence; however, the mutant AgQl (Q496E) was still clearly recognized by the Mab AgQ 1 -1. Surprisingly, replacement of the adjacent amino acid, in mutant AgQ 1 (C495A), resulted in poor recognition by Mab AgQ 1-1, and AgQl(C495A) could not form the gH/gL/gQl/gQ2 complex. Furthermore, the binding ability of mutant AgQl (L494A) with CD46 decreased, although it could form the gH/gL/gQl/gQ2 complex and it showed clear reactivity to Mab AgQ 1 -1. These data indicated that amino acid residues 494 to 497 of AgQl were critical for the recognition by Mab AgQ 1-1 and essential for AgQl's functional conformation. [ABSTRACT FROM AUTHOR]

Balò's concentric sclerosis (BCS) is a rare primary demyelinating disease of central nervous system (CNS) and is considered to be a variant of multiple sclerosis (MS). It is characterized by a severe, rapidly evolving course with CNS lesions consisting of concentric rings of demyelination alternating with myelination in the white matter. We report a patient with BCS from mainland China diagnosed on magnetic resonance imaging (MRI) findings. In addition to two contrast enhanced open ring lesions. MRI also showed multiple small white matter lesions in both the hemispheres. The patient had a good response to corticosteroids and had a benign prognosis during a follow-up period of two years. [ABSTRACT FROM AUTHOR]

Human herpesvirus 6 (HHV-6) is a T cell-tropic betaherpesvirus. HHV-6 can be classified into two variants, HHV-6A and HHV-6B, based on differences in their genetic, antigenic, and growth characteristics and cell tropisms. The function of HHV-6B should be analyzed more in its life cycle, as more than 90% of people have the antibodies for HHV-6B but not HHV-6A. It has been shown that the cellular receptor for HHV-6A is human CD46 and that the viral ligand for CD46 is the envelope glycoprotein complex gH/gL/gQ1/gQ2; however, the receptor-ligand pair used by HHV-6B is still unknown. In this study, to identify the glycoprotein(s) important for HHV-6B entry, we generated monoclonal antibodies (MAbs) that inhibit infection by HHV-6B. Most of these MAbs were found to recognize gQ1, indicating that HHV-6B gQ1 is critical for virus entry. Interestingly, the recognition of gQ1 by the neutralizing MAb was enhanced by coexpression with gQ2. Moreover, gQ1 deletion or point mutants that are not recognized by the MAb could nonetheless associate with gQ2, indicating that although the MAb recognized the conformational epitope of gQ1 exposed by the gQ2 interaction, this epitope was not related to the gQ2 binding domain. Our study shows that HHV-6B gQ1 is likely a ligand for the HHV- 6B receptor, and the recognition site for this MAb will be a promising target for antiviral agents. [ABSTRACT FROM AUTHOR]