scholarly journals Herpes Simplex Virus 2 UL45 Is a Type II Membrane Protein

1998 ◽  
Vol 72 (5) ◽  
pp. 4430-4433 ◽  
Author(s):  
Adam S. Cockrell ◽  
Martin I. Muggeridge
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Membrane Protein ◽  
Integral Membrane Protein ◽  
Type Ii ◽  
Glycosylation Sites ◽  
Infected Cells ◽  
Membrane Spanning ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

ABSTRACT In addition to eleven glycoproteins, the herpes simplex virus type 2 (HSV-2) genome encodes several proteins with potential membrane-spanning segments but no asparagine-linked carbohydrates. One of these is UL45. Fractionation of infected cells showed that HSV-2 UL45 is an integral membrane protein, and analysis of UL45 mutants with potential glycosylation sites showed that it has a type II membrane orientation, the first HSV protein known to have this orientation. Furthermore, it is detectable in infected cells at a time similar to that when glycoproteins gB and gD are detected, consistent with a role in cell-cell fusion, which has previously been found for HSV-1 UL45.

scholarly journals The UL34 gene product of herpes simplex virus type 2 is a tail-anchored type II membrane protein that is significant for virus envelopment

2000 ◽  
Vol 81 (10) ◽  
pp. 2397-2405 ◽  
Author(s):  
C. Shiba ◽  
T. Daikoku ◽  
F. Goshima ◽  
H. Takakuwa ◽  
Y. Yamauchi ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Membrane Protein ◽  
Herpes Simplex Virus Type ◽  
Deletion Mutant ◽  
Type Ii ◽  
Infected Cells ◽  
Simplex Virus ◽  
Type Ii Membrane Protein

The UL34 gene of herpes simplex virus type 2 (HSV-2) is highly conserved in the herpesvirus family. The UL34 gene product was identified In lysates of HSV-2-infected cells as protein species with molecular masses of 31 and 32·5 kDa, the latter being a phosphorylated product. Synthesis of these proteins occurred at late times post-infection and was highly dependent on viral DNA synthesis. Immunofluorescence assays revealed that the UL34 protein was localized in the cytoplasm in a continuous net-like structure, closely resembling the staining pattern of the endoplasmic reticulum (ER), in both HSV-2-infected cells and in cells transiently expressing UL34 protein. Deletion mutant analysis showed that this colocalization required the C terminus of the UL34 protein. The UL34 protein associated with virions but not with A, B or C capsids. We treated virions, HSV-2-infected cells and cells expressing the UL34 protein with a protease in order to examine the topology of the UL34 protein. In addition, we constructed UL34 deletion mutant proteins and examined their intracellular localization. Our data strongly support the hypothesis that the UL34 protein is inserted into the viral envelope as a tail-anchored type II membrane protein and is significant for virus envelopment.

scholarly journals Elimination of HSV-2 infected cells is mediated predominantly by paracrine effects of tissue-resident T cell derived cytokines

2019 ◽  
Author(s):  
Pavitra Roychoudhury ◽  
David A Swan ◽  
Elizabeth Duke ◽  
Lawrence Corey ◽  
Jia Zhu ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Lesion Size ◽  
Viral Kinetics ◽  
Paracrine Effects ◽  
Alarm Signaling ◽  
Infected Cells ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

AbstractThe mechanisms underlying rapid elimination of herpes simplex virus-2 (HSV-2) in the human genital tract despite low tissue-resident CD8+ T-cell density (TRM) are unknown. We analyzed shedding episodes during chronic HSV-2 infection: viral clearance always occurred within 24 hours of detection even if viral load exceeded 107HSV DNA copies; surges in granzyme B and interferon-γoccurred within the early hours after reactivation. We next developed a mathematical model of an HSV-2 genital ulcer to integrate mechanistic observations of TRMin situproliferation, trafficking, cytolytic effects and cytokine alarm signaling from murine studies with viral kinetics, histopathology and lesion size data from humans. A sufficiently high density of HSV-2 specific TRMpredicted rapid contact-mediated elimination of infected cells. At lower TRMdensities, TRMmust initiate a rapidly diffusing, polyfunctional cytokine response in order to eliminate of a majority of infected cells and eradicate briskly spreading HSV-2 infection.One Sentence SummaryControl of herpes simplex virus-2 is primarily mediated by rapidly diffusing cytokines secreted by tissue-resident T cells.

scholarly journals Tissue-resident T cell–derived cytokines eliminate herpes simplex virus-2–infected cells

2020 ◽  
Vol 130 (6) ◽  
pp. 2903-2919 ◽  
Author(s):  
Pavitra Roychoudhury ◽  
David A. Swan ◽  
Elizabeth Duke ◽  
Lawrence Corey ◽  
Jia Zhu ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Infected Cells ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

scholarly journals Thin-layer immunoassay for determination of antibodies to herpes simplex virus

1979 ◽  
Vol 9 (3) ◽  
pp. 317-322
Author(s):  
S Jeansson ◽  
H Elwing ◽  
L A Nilsson
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thin Layer ◽  
False Negative ◽  
Virus Antigen ◽  
Herpes Simplex Virus 1 ◽  
Infected Cells ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

Thin-layer immunoassay (TIA) is a simple serological technique suitable for analysis of large numbers of samples. In this study, TIA was evaluated for determination of antibodies to herpes simplex virus. Herpes simplex virus antigen used in TIA was purified from material released from virus-infected cells. The results obtained by TIA were compared with those obtained by neutralization and complement fixation tests. TIA was found to be as sensitive as the neutralization test for demonstration of herpes simplex virus antibodies. No false-negative or -positive reactions were observed. In primary herpes simplex virus-1 infections, an antibody response was demonstrated by TIA, whereas antibodies could not be demonstrated in patients with primary herpes simplex virus-2 infections.

scholarly journals Identification and Characterization of the UL56 Gene Product of Herpes Simplex Virus Type 2

2002 ◽  
Vol 76 (13) ◽  
pp. 6718-6728 ◽  
Author(s):  
Tetsuo Koshizuka ◽  
Fumi Goshima ◽  
Hiroki Takakuwa ◽  
Naoki Nozawa ◽  
Tohru Daikoku ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Golgi Apparatus ◽  
Gene Product ◽  
Type Ii ◽  
Cytoplasmic Vesicles ◽  
Infected Cells ◽  
Simplex Virus ◽  
Type Ii Membrane Protein

ABSTRACT The UL56 gene product of herpes simplex virus (HSV) has been shown to play an important role in viral pathogenicity. However, the properties and functions of the UL56 protein are little understood. We raised rabbit polyclonal antisera specific for the UL56 protein of HSV type 2 (HSV-2) and examined its expression and properties. The gene product was identified as three polypeptides with apparent molecular masses ranging from 32 to 35 kDa in HSV-2-infected cells, and at least one species was phosphorylated. Studies of their origins showed that the UL56 protein of HSV-2 is also translated from the upstream in-frame methionine codon that is not present in the HSV-1 genome. Synthesis was first detected at 6 h postinfection and was not abolished by the viral DNA synthesis inhibitor phosphonoacetic acid. Indirect immunofluorescence studies revealed that the UL56 protein localized to both the Golgi apparatus and cytoplasmic vesicles in HSV-2-infected and single UL56-expressing cells. Deletion mutant analysis showed that the C-terminal hydrophobic region of the protein was required for association with the cytoplasmic membrane and that the N-terminal proline-rich region was important for its translocation to the Golgi apparatus and cytoplasmic vesicles. Moreover, the results of protease digestion assays and sucrose gradient fractionation strongly suggested that UL56 is a tail-anchored type II membrane protein associated with lipid rafts. We thus hypothesized that the UL56 protein, as a tail-anchored type II membrane protein, may be involved in vesicular trafficking in HSV-2-infected cells.

scholarly journals Herpes simplex virus type 2 membrane protein UL56 associates with the kinesin motor protein KIF1A

2005 ◽  
Vol 86 (3) ◽  
pp. 527-533 ◽  
Author(s):  
Tetsuo Koshizuka ◽  
Yasushi Kawaguchi ◽  
Yukihiro Nishiyama
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Membrane Protein ◽  
Transmembrane Domain ◽  
Yeast Two Hybrid ◽  
Infected Cells ◽  
Simplex Virus ◽  
Two Hybrid

The herpes simplex virus UL56 gene product is a C-terminal-anchored, type II membrane protein of unknown function. UL56 was found to interact with KIF1A, a member of the kinesin-3 family, in a yeast two-hybrid screen and a GST pull-down assay. KIF1A mediates the transport of synaptic vesicle precursors and is essential for the function and viability of neurons. When overexpressed, KIF1A co-localized with full-sized UL56, but no clear co-localization was observed when co-expressed with the UL56 mutant protein lacking its C-terminal transmembrane domain (TMD). Although the C-terminal TMD was not essential for the interaction with KIF1A in the yeast two-hybrid screen and GST pull-down assays, these results indicate that the C-terminal TMD, as well as aa 69–217, of UL56 are important for the interaction with KIF1A in vivo. The hypothesis that the UL56 protein affects vesicular trafficking in infected cells, potentially by acting as a receptor for motor proteins in neurons, is discussed.

scholarly journals Antiviral Activity of a Single-Domain Antibody Immunotoxin Binding to Glycoprotein D of Herpes Simplex Virus 2

2014 ◽  
Vol 59 (1) ◽  
pp. 527-535 ◽  
Author(s):  
Eileen M. Geoghegan ◽  
Hong Zhang ◽  
Prashant J. Desai ◽  
Arya Biragyn ◽  
Richard B. Markham
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Single Domain ◽  
Surface Glycoprotein ◽  
Glycoprotein D ◽  
Single Domain Antibody ◽  
Domain Antibody ◽  
Infected Cells ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

ABSTRACTDespite years of research dedicated to preventing the sexual transmission of herpes simplex virus 2 (HSV-2), there is still no protective vaccine or microbicide against one of the most common sexually transmitted infections in the world. Using a phage display library constructed from a llama immunized with recombinant HSV-2 glycoprotein D, we identified a single-domain antibody VHH, R33, which binds to the viral surface glycoprotein D. Although R33 does not demonstrate any HSV-2 neutralization activityin vitro, when expressed with the cytotoxic domain of exotoxin A, the resulting immunotoxin (R33ExoA) specifically and potently kills HSV-2-infected cells, with a 50% neutralizing dilution (IC50) of 6.7 nM. We propose that R33ExoA could be used clinically to prevent transmission of HSV-2 through killing of virus-producing epithelial cells during virus reactivation. R33 could also potentially be used to deliver other cytotoxic effectors to HSV-2-infected cells.

scholarly journals Rapid localized spread and immunologic containment define Herpes simplex virus-2 reactivation in the human genital tract

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Joshua T Schiffer ◽  
David Swan ◽  
Ramzi Al Sallaq ◽  
Amalia Magaret ◽  
Christine Johnston ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Genital Tract ◽  
Time Intervals ◽  
Host Immune Responses ◽  
Spatial Propagation ◽  
Infected Cells ◽  
Episode Duration ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

Herpes simplex virus-2 (HSV-2) is shed episodically, leading to occasional genital ulcers and efficient transmission. The biology explaining highly variable shedding patterns, in an infected person over time, is poorly understood. We sampled the genital tract for HSV DNA at several time intervals and concurrently at multiple sites, and derived a spatial mathematical model to characterize dynamics of HSV-2 reactivation. The model reproduced heterogeneity in shedding episode duration and viral production, and predicted rapid early viral expansion, rapid late decay, and wide spatial dispersion of HSV replication during episodes. In simulations, HSV-2 spread locally within single ulcers to thousands of epithelial cells in <12 hr, but host immune responses eliminated infected cells in <24 hr; secondary ulcers formed following spatial propagation of cell-free HSV-2, allowing for episode prolongation. We conclude that HSV-2 infection is characterized by extremely rapid virological growth and containment at multiple contemporaneous sites within genital epithelium.

scholarly journals A 3-O-Sulfated Heparan Sulfate Binding Peptide Preferentially Targets Herpes Simplex Virus 2-Infected Cells

2012 ◽  
Vol 86 (12) ◽  
pp. 6434-6443 ◽  
Author(s):  
M. M. Ali ◽  
G. A. Karasneh ◽  
M. J. Jarding ◽  
V. Tiwari ◽  
D. Shukla
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Heparan Sulfate ◽  
Binding Peptide ◽  
Infected Cells ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

Assembly of VP26 in herpes simplex virus-1 capsid implicated by 3-D structure of recombinant capsid

1995 ◽  
Vol 53 ◽  
pp. 840-841
Author(s):  
Z. Hong Zhou ◽  
Jing He ◽  
Joanita Jakana ◽  
J. D. Tatman ◽  
Frazer J. Rixon ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
3D Structure ◽  
Structure Study ◽  
Herpes Simplex Virus 1 ◽  
Shell Proteins ◽  
Life Threatening ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus-1 (HSV-1) is a ubiquitous virus which is implicated in diseases ranging from self-curing cold sores to life-threatening infections. The 2500 Å diameter herpes virion is composed of a glycoprotein spike containing, lipid envelope, enclosing a protein layer (the tegument) in which is embedded the capsid (which contains the dsDNA genome). The B-, and A- and C-capsids, representing different morphogenetic stages in HSV-1 infected cells, are composed of 7, and 5 structural proteins respectively. The three capsid types are organized in similar T=16 icosahedral shells with 12 pentons, 150 hexons, and 320 connecting triplexes. Our previous 3D structure study at 26 Å revealed domain features of all these structural components and suggested probable locations for the outer shell proteins, VP5, VP26, VP19c and VP23. VP5 makes up most of both pentons and hexons. VP26 appeared to bind to the VP5 subunit in hexon but not to that in penton.

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