scholarly journals Features of Human Herpesvirus-6A and -6B Entry

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Takahiro Maeki ◽  
Yasuko Mori
Keyword(s):  
Cell Membrane ◽  
Viral Entry ◽  
Target Cell ◽  
Human Herpesvirus ◽  
Target Cells ◽  
Cellular Receptor ◽  
Schematic Model ◽  
Human Herpesvirus 6 ◽  
Detailed Mechanism ◽  
Target Cell Membrane

Human herpesvirus-6 (HHV-6) is a T lymphotropic herpesvirus belonging to theBetaherpesvirinaesubfamily. HHV-6 was long classified into variants A and B (HHV-6A and HHV-6B); however, recently, HHV-6A and HHV-6B were reclassified as different species. The process of herpesvirus entry into target cells is complicated, and in the case of HHV-6A and HHV-6B, the detailed mechanism remains to be elucidated, although both viruses are known to enter cells via endocytosis. In this paper, (1) findings about the cellular receptor and its ligand for HHV-6A and HHV-6B are summarized, and (2) a schematic model of HHV-6A’s replication cycle, including its entry, is presented. In addition, (3) reports showing the importance of lipids in both the HHV-6A envelope and target-cell membrane for viral entry are reviewed, and (4) glycoproteins involved in cell fusion are discussed.

scholarly journals Human Herpesvirus 6 Variant A but Not Variant B Induces Fusion from Without in a Variety of Human Cells through a Human Herpesvirus 6 Entry Receptor, CD46

2002 ◽  
Vol 76 (13) ◽  
pp. 6750-6761 ◽  
Author(s):  
Yasuko Mori ◽  
Tsukasa Seya ◽  
Hong Lan Huang ◽  
Pilailuk Akkapaiboon ◽  
Panadda Dhepakson ◽  
...  
Keyword(s):  
Human Herpesvirus ◽  
Syncytium Formation ◽  
Human Cells ◽  
Target Cells ◽  
Functional Difference ◽  
Human Herpesvirus 6 ◽  
Fusion Event ◽  
Target Cell Membrane ◽  
Herpesvirus 6 ◽  
Entry Receptor

ABSTRACT Human herpesvirus 6 (HHV-6) is a lymphotropic betaherpesvirus that productively infects T cells and monocytes. HHV-6 isolates can be differentiated into two groups, variants A and B (HHV-6A and HHV-6B). Here, we show a functional difference between HHV-6A and -6B in that HHV-6A induced syncytium formation of diverse human cells but HHV-6B did not. The syncytium formation induced by HHV-6A was observed 2 h after infection; moreover, it was found in the presence of cycloheximide, indicating that HHV-6A induced fusion from without (FFWO) in the target cells. Furthermore, the fusion event was dependent on the expression of the HHV-6 entry receptor, CD46, on the target cell membrane. In addition, we determined that short consensus repeat 2 (SCR2), -3, and -4 of the CD46 ectodomain were essential for the formation of the virus-induced syncytia. Monoclonal antibodies against glycoproteins B and H of HHV-6A inhibited the fusion event, indicating that the syncytium formation induced by HHV-6A required glycoproteins H and B. These findings suggest that FFWO, which HHV-6A induced in a variety of cell lines, may play an important role in the pathogenesis of HHV-6A, not only in lymphocytes but also in various tissues, because CD46 is expressed ubiquitously in human tissues.

scholarly journals In Vivo Efficacy of Measles Virus Fusion Protein-Derived Peptides Is Modulated by the Properties of Self-Assembly and Membrane Residence

2016 ◽  
Vol 91 (1) ◽  
Author(s):  
T. N. Figueira ◽  
L. M. Palermo ◽  
A. S. Veiga ◽  
D. Huey ◽  
C. A. Alabi ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Target Cell ◽  
Self Assembly ◽  
Measles Virus ◽  
Structural Transition ◽  
Target Cells ◽  
Fusion Inhibitor ◽  
Inhibitory Peptides ◽  
Target Cell Membrane

ABSTRACT Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad repeat (HR) regions of F can inhibit MV infection at the entry stage. In previous work, we have generated potent MV fusion inhibitors by dimerizing the F-derived peptides and conjugating them to cholesterol. We have shown that prophylactic intranasal administration of our lead fusion inhibitor efficiently protects from MV infection in vivo. We show here that peptides tagged with lipophilic moieties self-assemble into nanoparticles until they reach the target cells, where they are integrated into cell membranes. The self-assembly feature enhances biodistribution and the half-life of the peptides, while integration into the target cell membrane increases fusion inhibitor potency. These factors together modulate in vivo efficacy. The results suggest a new framework for developing effective fusion inhibitory peptides. IMPORTANCE Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. We show here that specific biophysical properties regulate the in vivo efficacy of MV F-derived peptides.

scholarly journals Adenylate cyclase toxin translocates across target cell membrane without forming a pore

2010 ◽  
Vol 75 (6) ◽  
pp. 1550-1562 ◽  
Author(s):  
Adriana Osickova ◽  
Jiri Masin ◽  
Catherine Fayolle ◽  
Jan Krusek ◽  
Marek Basler ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Adenylate Cyclase ◽  
Target Cell ◽  
Target Cell Membrane ◽  
Adenylate Cyclase Toxin

Enhanced cellular uptake and tumor penetration of nanoparticles by imprinting the “hidden” part of membrane receptors for targeted drug delivery

2017 ◽  
Vol 53 (81) ◽  
pp. 11114-11117 ◽  
Author(s):  
Shan Peng ◽  
Yahua Wang ◽  
Na Li ◽  
Chong Li
Keyword(s):  
Drug Delivery ◽  
Cell Membrane ◽  
Cellular Uptake ◽  
Target Cell ◽  
Targeted Drug Delivery ◽  
Transmembrane Domain ◽  
Membrane Receptors ◽  
Tumor Penetration ◽  
Target Cell Membrane ◽  
Targeted Drug

Biting deep into the target cell membrane: nanoparticles targeting the transmembrane domain by trifluoroethanol-assisted epitope imprinting.

scholarly journals Calcium ion concentrations and DNA fragmentation in target cell destruction by murine cloned cytotoxic T lymphocytes.

1988 ◽  
Vol 167 (2) ◽  
pp. 514-527 ◽  
Author(s):  
N L Allbritton ◽  
C R Verret ◽  
R C Wolley ◽  
H N Eisen
Keyword(s):  
Dna Fragmentation ◽  
Target Cell ◽  
Target Cells ◽  
Pronounced Increase ◽  
Ion Concentrations ◽  
Emission Maximum ◽  
Cytolytic Granule ◽  
Target Cell Membrane ◽  
Membrane Changes ◽  
High Level

To investigate the destruction of target cells by murine CTLs, we examined intracellular Ca2+ concentrations ([Ca2+]i) and DNA fragmentation in target cells. Changes in [Ca2+]i were followed by flow cytometry by loading the cells with indo-1, a Ca2+-binding fluorescent dye, and determining the ration of fluorescence intensities at 405 nm (emission maximum for Ca2+-bound dye) over 480 nm (emission maximum for the free dye). Within minutes after interacting with the cytolytic granule fraction that had been isolated from CTLs, [Ca2+]i in target cells was strikingly increased. A pronounced increase in [Ca2+]i was also observed in target cells when they were specifically recognized by intact CTLs. Since ionomycin, a Ca2+ ionophore, caused a similar increase in [Ca2+]i and lysed cells (provided that extracellular Ca2+ was present), it appears that a sustained high level of [Ca2+]i is cytolytic. In contrast with other cells, CTLs, which have been shown to be refractory to granule-mediated lysis and to be poor targets for other CTLs, did not manifest an elevation in [Ca2+]i when they were similarly loaded with indo-1 and treated with isolated granules. The characteristic cleavage of target cell DNA into nucleosome-sized fragments was also induced by isolated granules as well as by valinomycin, a K+ ionophore, but not by ionomycin. The results support the view that lysis of most target cells by cloned CTLs is due primarily to target cell membrane changes that are fundamentally equivalent to the formation of nonspecific ion channels. The resulting large increase in [Ca2+]i is probably responsible for target cell lysis; and changes in intracellular ion concentrations also appear to be responsible for DNA fragmentation, probably by activating endogenous target cell endonucleases.

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