scholarly journals Structural Rearrangement within an Enveloped Virus upon Binding to the Host Cell

2008 ◽  
Vol 82 (21) ◽  
pp. 10429-10435 ◽  
Author(s):  
David G. Meckes ◽  
John W. Wills
Keyword(s):  
Cell Attachment ◽  
Structural Rearrangement ◽  
Viral Envelope ◽  
Viral Glycoprotein ◽  
Glycoprotein C ◽  
Enveloped Virus ◽  
Host Signaling ◽  
Infected Cells ◽  
Internal Change ◽  
Simplex Virus

ABSTRACT We have made the surprising discovery that the interactions of herpes simplex virus with its initial cell attachment receptor induce a rapid and highly efficient structural change in the tegument, the region of the virion situated between the membrane and the capsid. It has been known for nearly a decade that viruses can trigger host signaling pathways when they bind to receptors on the cell surface; however, until now there has been no evidence that a signal can be sent in reverse—from the “outside in”—across a viral membrane. Evidence for this signaling event was found during studies of UL16, a tegument protein that is conserved among all the herpesviruses. Previous work has demonstrated that UL16 is bound to capsids isolated from the cytoplasm of infected cells, but this interaction is destabilized during subsequent egress steps, leading to release of the extracellular virion. Pretreatment with N-ethylmaleimide, a small, membrane-permeating compound that covalently modifies free cysteines, restabilizes the interaction, thereby permitting the capsid-UL16 complex to be isolated following disruption of virions with NP-40. In the experiments described here, we found that the natural signal for release of UL16 from capsids is sent when virions merely bind to cells at 4°C. The internal change was also observed upon binding to immobilized heparin in a manner that requires viral glycoprotein C. This represents the first example of signaling across a viral envelope following receptor binding.

scholarly journals Copatching and Lipid Raft Association of Different Viral Glycoproteins Expressed on the Surfaces of Pseudorabies Virus-Infected Cells

2004 ◽  
Vol 78 (10) ◽  
pp. 5279-5287 ◽  
Author(s):  
Herman W. Favoreel ◽  
Thomas C. Mettenleiter ◽  
Hans J. Nauwynck
Keyword(s):  
Lipid Rafts ◽  
Lipid Raft ◽  
Plasma Membranes ◽  
Pseudorabies Virus ◽  
Viral Proteins ◽  
Viral Envelope ◽  
Viral Glycoprotein ◽  
Monospecific Antibody ◽  
Infected Cells ◽  
Simplex Virus

ABSTRACT Pseudorabies virus (PRV) is a swine alphaherpesvirus that is closely related to human herpes simplex virus (HSV). Both PRV and HSV express a variety of viral envelope glycoproteins in the plasma membranes of infected cells. Here we show that at least four major PRV glycoproteins (gB, gC, gD, and gE) in the plasma membrane of infected swine kidney cells and monocytes seem to be linked, since monospecific antibody-induced patching of any one of these proteins results in copatching of the others. Further, for all four PRV glycoproteins, monospecific antibody-induced patches were enriched in GM1, a typical marker of lipid raft microdomains, but were excluded for transferrin receptor, a nonraft marker, suggesting that these viral proteins may associate with lipid rafts. However, only gB and, to a lesser extent, gE were found in lipid raft fractions by using detergent floatation assays, indicating that gC and gD do not show strong lipid raft association. Addition of methyl-β-cyclodextrin (MCD), a cholesterol-depleting agent that is commonly used to disrupt lipid rafts, only slightly reduced copatching efficiency between the different viral proteins, indicating that other factors, perhaps tegument-glycoprotein interactions, may be important for the observed copatching events. On the other hand, MCD strongly reduced polarization of the antibody-induced viral glycoprotein patches to a cap structure, a gE-dependent process that has been described for specific PRV- and HSV-infected cells. Therefore, we hypothesize that efficient gE-mediated capping of antibody-antigen patches may require the lipid raft-associated signal transduction machinery.

scholarly journals A Herpes Simplex Virus 1 (McKrae) Mutant Lacking the Glycoprotein K Gene Is Unable To Infect via Neuronal Axons and Egress from Neuronal Cell Bodies

mBio ◽  
2012 ◽  
Vol 3 (4) ◽  
Author(s):  
Andrew T. David ◽  
Ahmad Saied ◽  
Anu Charles ◽  
Ramesh Subramanian ◽  
Vladimir N. Chouljenko ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Recombinant Virus ◽  
Neuronal Cell ◽  
Viral Envelope ◽  
Viral Glycoprotein ◽  
Herpes Simplex Virus 1 ◽  
Neuronal Cell Bodies ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTWe have shown that the herpes simplex virus 1 (HSV-1) gK gene is essential for efficient replication and spread in the corneal epithelium and trigeminal ganglion neuroinvasion in mice (A. T. David, A. Baghian, T. P. Foster, V. N. Chouljenko, and K. G. Kousoulas, Curr. Eye Res. 33:455–467, 2008). To further investigate the role of gK in neuronal infection, we utilized a microfluidic chamber system separating neuronal cell bodies and axonal termini. HSV-1 (McKrae) engineered virus constitutively expressing enhanced green fluorescence protein (GFP) was efficiently transmitted in both a retrograde and an anterograde manner. These results were corroborated by expression of virion structural proteins in either chamber, as well as detection of viral genomes and infectious viruses. In contrast, efficient infection of either chamber with a gK-null virus did not result in infection of the apposed chamber. These results show that gK is an important determinant in virion axonal infection. Moreover, the inability of the gK-null virus to be transmitted in an anterograde manner suggests that virions acquire cytoplasmic envelopes prior to entering axons.IMPORTANCEHerpes simplex virus 1 (HSV-1) enters mucosal epithelial cells and neurons via fusion of the viral envelope with cellular membranes, mediated by viral glycoprotein B (gB) in cooperation with other viral glycoproteins. Retrograde transport of virions to neuronal cell bodies (somata) establishes lifelong latent infection in ganglionic neurons. We have previously reported that gK binds gB and is required for gB-mediated membrane fusion (Jambunatathan et al., J. Virol. 85:12910–12918, 2011; V. N. Chouljenko, A. V. Iyer, S. Chowdhury, J. Kim, and K. G. Kousoulas, J. Virol. 84:8596–8606, 2010). In the current study, we constructed a recombinant virus with the gK gene deleted in the highly virulent ocular HSV-1 strain McKrae. This recombinant virus failed to infect rat ganglionic neuronal axons alone or cocultured with Vero cells in microfluidic chambers. In addition, lack of gK expression prevented anterograde transmission of virions. These results suggest that gK is a critical determinant for neuronal infection and transmission.

scholarly journals Ocular disease pattern induced by herpes simplex virus is genetically determined by a specific region of viral DNA.

1982 ◽  
Vol 155 (2) ◽  
pp. 475-489 ◽  
Author(s):  
Y M Centifanto-Fitzgerald ◽  
T Yamaguchi ◽  
H E Kaufman ◽  
M Tognon ◽  
B Roizman
Keyword(s):  
Ocular Disease ◽  
Donor Strain ◽  
Glycoprotein C ◽  
Rabbit Eye ◽  
Disease Pattern ◽  
Infected Cells ◽  
Severity Of The Disease ◽  
Simplex Virus ◽  
Genetically Determined ◽  
Hsv 1

The pattern of ocular disease produced in the rabbit eye by HSV-1 (F) and HSV-1(MP) strains and recombinants F(MP)A, F(MP)B, F(MP)C, F(MP)D, F(MP)E, and F(MP)F was studied. The characteristics of ocular herpetic disease such as morphology of dendritic ulcers, severity of epithelial disease and incidence and duration of stromal disease produced in the rabbit eye are genetically determined by the virus strain. Our studies show that transfer of a defined part of the genome of the stromal disease-producing virus, HSV-1(MP), to the genome of an epithelial disease-producing virus, HSV-1(F), yielded recombinants with one or more of the disease characteristics of the donor strain. Specifically, recombinant F(MP)D produced lesions characteristic of the donor HSV-1(MP) strain; recombinants F(MP)C and F(MP)E produced stromal disease approaching the severity of the disease produced by the donor HSV-1(MP) strain, and only recombinants F(MP)A and F(MP)B retained the typically elongate lesions of the recipient HSV-1(F), whereas the recombinant strain F(MP)F produced no disease. The viral functions pertaining to the ocular disease pattern map between 0.70 and 0.83 map units in HSV-1 DNA within the BglII F DNA fragment. The pattern of stromal disease is independent of the production of glycoprotein C and fusion of HEp-2-infected cells. The functions relating to these aspects of ocular disease segregate but are closely linked.

Glycoprotein C of herpes simplex virus 1 acts as a receptor for the C3b complement component on infected cells

Nature ◽  
1984 ◽  
Vol 309 (5969) ◽  
pp. 633-635 ◽  
Author(s):  
Harvey M. Friedman ◽  
Gary H. Cohen ◽  
Roselyn J. Eisenberg ◽  
Cynthia A. Seidel ◽  
Douglas B. Cines
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Complement Component ◽  
Herpes Simplex Virus 1 ◽  
Glycoprotein C ◽  
Infected Cells ◽  
Simplex Virus

scholarly journals Herpes Simplex Virus 1 Protein Kinase Us3 Phosphorylates Viral Envelope Glycoprotein B and Regulates Its Expression on the Cell Surface

2008 ◽  
Vol 83 (1) ◽  
pp. 250-261 ◽  
Author(s):  
Akihisa Kato ◽  
Jun Arii ◽  
Ikuo Shiratori ◽  
Hiroomi Akashi ◽  
Hisashi Arase ◽  
...  
Keyword(s):  
Cell Surface ◽  
Envelope Glycoprotein ◽  
Surface Expression ◽  
Viral Envelope ◽  
Cell Surface Expression ◽  
Wild Type ◽  
Herpes Simplex Virus 1 ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Us3 is a serine-threonine protein kinase encoded by herpes simplex virus 1 (HSV-1). As reported here, we attempted to identify the previously unreported physiological substrate of Us3 in HSV-1-infected cells. Our results were as follows. (i) Bioinformatics analysis predicted two putative Us3 phosphorylation sites in the viral envelope glycoprotein B (gB) at codons 557 to 562 (RRVSAR) and codons 884 to 889 (RRNTNY). (ii) In in vitro kinase assays, the threonine residue at position 887 (Thr-887) in the gB domain was specifically phosphorylated by Us3, while the serine residue at position 560 was not. (iii) The phosphorylation of gB Thr-887 in Vero cells infected with wild-type HSV-1 was specifically detected using an antibody that recognized phosphorylated serine or threonine residues with arginine at the −3 and −2 positions. (iv) The phosphorylation of gB Thr-887 in infected cells was dependent on the kinase activity of Us3. (v) The replacement of Thr-887 with alanine markedly upregulated the cell surface expression of gB in infected cells, whereas replacement with aspartic acid, which sometimes mimics constitutive phosphorylation, restored the wild-type phenotype. The upregulation of gB expression on the cell surface also was observed in cells infected with a recombinant HSV-1 encoding catalytically inactive Us3. These results supported the hypothesis that Us3 phosphorylates gB and downregulates the cell surface expression of gB in HSV-1-infected cells.

scholarly journals Maintenance of Endoplasmic Reticulum (ER) Homeostasis in Herpes Simplex Virus Type 1-Infected Cells through the Association of a Viral Glycoprotein with PERK, a Cellular ER Stress Sensor

2007 ◽  
Vol 81 (7) ◽  
pp. 3377-3390 ◽  
Author(s):  
Matthew Mulvey ◽  
Carolina Arias ◽  
Ian Mohr
Keyword(s):  
Endoplasmic Reticulum ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Er Stress ◽  
Herpes Simplex Virus Type ◽  
Viral Glycoprotein ◽  
Infected Cells ◽  
Simplex Virus ◽  
Er Homeostasis

ABSTRACTIn the efforts of viruses to dominate and control critical cellular pathways, viruses generate considerable intracellular stress within their hosts. In particular, the capacity of resident endoplasmic reticulum (ER) chaperones to properly process the acute increase in client protein load is significantly challenged. Such alterations typically induce the unfolded protein response, one component of which acts through IRE1 to restore ER homeostasis by expanding the folding capabilities, whereas the other arm activates the eIF-2α (α subunit of eukaryotic initiation factor 2) kinase PERK to transiently arrest production of new polypeptide clientele. Viruses, such as herpes simplex virus type 1 (HSV-1), however, go to great lengths to prevent the inhibition of translation resulting from eIF-2α phosphorylation. Here, we establish that PERK, but not IRE1, resists activation by acute ER stress in HSV-1-infected cells. This requires the ER luminal domain of PERK, which associates with the viral glycoprotein gB. Strikingly, gB regulates viral protein accumulation in a PERK-dependent manner. This is the first description of a virus-encoded PERK-specific effector and defines a new strategy by which viruses are able to maintain ER homeostasis.

scholarly journals The Herpes Simplex Virus 1 UL51 Protein Interacts with the UL7 Protein and Plays a Role in Its Recruitment into the Virion

2014 ◽  
Vol 89 (6) ◽  
pp. 3112-3122 ◽  
Author(s):  
Richard J. Roller ◽  
Rachel Fetters
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Assembly ◽  
Viral Glycoprotein ◽  
Herpes Simplex Virus 1 ◽  
Independent Functions ◽  
The Face ◽  
Infected Cells ◽  
Simplex Virus ◽  
Cell Spread

ABSTRACTThe alphaherpesvirus UL51 protein is a tegument component that interacts with the viral glycoprotein E and functions at multiple steps in virus assembly and spread in epithelial cells. We show here that pUL51 forms a complex in infected cells with another conserved tegument protein, pUL7. This complex can form in the absence of other viral proteins and is largely responsible for recruitment of pUL7 to cytoplasmic membranes and into the virion tegument. Incomplete colocalization of pUL51 and pUL7 in infected cells, however, suggests that a significant fraction of the population of each protein is not complexed with the other and that they may accomplish independent functions.IMPORTANCEThe ability of herpesviruses to spread from cell to cell in the face of an immune response is critical for disease and shedding following reactivation from latency. Cell-to-cell spread is a conserved ability of herpesviruses, and the identification of conserved viral genes that mediate this process will aid in the design of attenuated vaccines and of novel therapeutics. The conserved UL51 gene of herpes simplex virus 1 plays important roles in cell-to-cell spread and in virus assembly in the cytoplasm, both of which likely depend on specific interactions with other viral and cellular proteins. Here we identify one of those interactions with the product of another conserved herpesvirus gene, UL7, and show that formation of this complex mediates recruitment of UL7 to membranes and to the virion.

scholarly journals Responses of Herpes Simplex Virus Type 1-Infected Cells to the Presence of Extracellular Antibodies: gE-Dependent Glycoprotein Capping and Enhancement in Cell-to-Cell Spread

2003 ◽  
Vol 77 (1) ◽  
pp. 701-708 ◽  
Author(s):  
Syed Monem Rizvi ◽  
Malini Raghavan
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Transmission ◽  
Dependent Manner ◽  
Viral Glycoprotein ◽  
Infected Cells ◽  
Simplex Virus ◽  
Cell Spread ◽  
Hsv 1

ABSTRACT Binding of anti-herpes simplex virus (HSV) immunoglobulin G (IgG) to HSV type 1 (HSV-1)-infected HEL and HEp-2 cells causes changes in surface viral glycoprotein distribution, resulting in a capping of all viral glycoproteins towards one pole of the cell. This occurs in a gE-dependent manner. In HEL cells, low concentrations of anti-HSV IgG also enhance cell-to-cell spread of wild-type HSV-1 but not of gE deletion mutant HSV-1. These observations raised the possibility that gE-dependent mechanisms exist that allow some HSV-1-infected cells to respond to the presence of extracellular antibodies by enhancing the antibody-resistant mode of virus transmission.

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