Herpes simplex virus turns off the TAP to evade host immunity

Nature ◽  
1995 ◽  
Vol 375 (6530) ◽  
pp. 411-415 ◽  
Author(s):  
Ann Hill ◽  
Pieter Jugovic ◽  
lan York ◽  
Gustav Russ ◽  
Jack Bennink ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Host Immunity ◽  
Simplex Virus

scholarly journals Herpes Simplex Virus γ34.5 Interferes with Autophagosome Maturation and Antigen Presentation in Dendritic Cells

mBio ◽  
2012 ◽  
Vol 3 (5) ◽  
Author(s):  
Philipe A. M. Gobeil ◽  
David A. Leib
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Host Immunity ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTThe cellular autophagy response induced by herpes simplex virus 1 (HSV-1) is countered by the viral γ34.5 protein. γ34.5 modulates autophagy by binding to the host autophagy protein Beclin-1 and through this binding inhibits the formation of autophagosomes in fibroblasts and neurons. In contrast, in this study dendritic cells (DCs) infected with HSV-1 showed an accumulation of autophagosomes and of the long-lived protein p62. No such accumulations were observed in DCs infected with a γ34.5-null virus or a virus lacking the Beclin-binding domain (BBD) of γ34.5. To explore this further, we established stably transduced DC lines to show that γ34.5 expression alone induced autophagosome accumulation yet prevented p62 degradation. In contrast, DCs expressing a BBD-deleted mutant of γ34.5 were unable to modulate autophagy. DCs expressing γ34.5 were less capable of stimulating T-cell activation and proliferation in response to intracellular antigens, demonstrating an immunological consequence of inhibiting autophagy. Taken together, these data show that in DCs, γ34.5 antagonizes the maturation of autophagosomes and T cell activation in a BBD-dependent manner, illustrating a unique interface between HSV and autophagy in antigen-presenting cells.IMPORTANCEHerpes simplex virus 1 (HSV-1) is a highly prevalent pathogen causing widespread morbidity and some mortality. HSV infections are lifelong, and there are no vaccines or antivirals to cure HSV infections. The ability of HSV to modulate host immunity is critical for its virulence. HSV inhibits host autophagy, a pathway with importance in many areas of health and disease. Autophagy is triggered by many microbes, some of which harness autophagy for replication; others evade autophagy or prevent it from occurring. Autophagy is critical for host defense, either by directly degrading the invading pathogen (“xenophagy”) or by facilitating antigen presentation to T cells. In this study, we show that HSV manipulates autophagy through an unsuspected mechanism with a functional consequence of reducing T cell stimulation. These data further our understanding of how HSV evades host immunity to persist for the lifetime of its host, facilitating its spread in the human population.

scholarly journals Reduced immune responses after vaccination with a recombinant herpes simplex virus type 1 vector in the presence of antiviral immunity

2005 ◽  
Vol 86 (9) ◽  
pp. 2401-2410 ◽  
Author(s):  
Henning Lauterbach ◽  
Christine Ried ◽  
Alberto L. Epstein ◽  
Peggy Marconi ◽  
Thomas Brocker
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Host Immunity ◽  
Vaccine Vectors ◽  
Simplex Virus ◽  
Hsv 1

Due to the continuous need for new vaccines, viral vaccine vectors have become increasingly attractive. In particular, herpes simplex virus type 1 (HSV-1)-based vectors offer many advantages, such as broad cellular tropism, large DNA-packaging capacity and the induction of pro-inflammatory responses. However, despite promising results obtained with HSV-1-derived vectors, the question of whether pre-existing virus-specific host immunity affects vaccine efficacy remains controversial. For this reason, the influence of pre-existing HSV-1-specific immunity on the immune response induced with a replication-defective, recombinant HSV-1 vaccine was investigated in vivo. It was shown that humoral as well as cellular immune responses against a model antigen encoded by the vaccine were strongly diminished in HSV-1-seropositive mice. This inhibition could be observed in mice infected with wild-type HSV-1 or with a replication-defective vector. Although these data clearly indicate that pre-existing antiviral host immunity impairs the efficacy of HSV-1-derived vaccine vectors, they also show that vaccination under these constraints might still be feasible.

scholarly journals Herpes Simplex Virus Vectors Elicit Durable Immune Responses in the Presence of Preexisting Host Immunity

2002 ◽  
Vol 76 (8) ◽  
pp. 3678-3687 ◽  
Author(s):  
Mark A. Brockman ◽  
David M. Knipe
Keyword(s):  
Escherichia Coli ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Proliferative Response ◽  
Host Immunity ◽  
Igg Antibody ◽  
Simplex Virus ◽  
Heterologous Antigens ◽  
Induce Antibody

ABSTRACT Herpes simplex virus (HSV) recombinants are being developed as vaccine vectors for the expression of heterologous antigens. There is concern, however, that preexisting HSV immunity may decrease their effectiveness. We have addressed this issue in an animal model. Immunized mice were inoculated with a replication-defective HSV-1 vector that expressed the Escherichia coli β-galactosidase protein as a model antigen. We assessed vector efficacy by analyzing the immunoglobulin G (IgG) antibody response and cellular proliferative response directed against β-galactosidase. We report that the ability of the vector to induce antibody or proliferative responses was not diminished by preexisting immunity to HSV. Of further note, the anti-HSV and anti-β-galactosidase IgG responses following vector administration were extremely durable in both immunized and naive mice. These results indicate that the ability of a replication-defective HSV-derived vaccine vector to elicit long-lived immune responses in mice is not impaired by prior HSV exposure.

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.

Application of EM to differentiate herpes virus from pox virus in genital specimens

1994 ◽  
Vol 52 ◽  
pp. 262-263
Author(s):  
K. Rekrut ◽  
K. Schleuter
Keyword(s):  
Tissue Culture ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Fresh Tissue ◽  
Culture Cells ◽  
Viral Transport ◽  
Carbon Coated ◽  
Immuno Assay ◽  
Simplex Virus ◽  
Enzyme Immuno Assay

Confirmation of herpes simplex virus (HSV) from genital lesions of obstetrical (OB) patients may affect both the management of the delivery and of the neonate.(l,2) During 1992 and 1993, 4,450 genital specimens from OB patients were submitted in viral transport media for herpes culture. The specimens were inoculated into MRC-5, Vero, and A-549 tissue culture tubes, incubated, and examined daily for 7 days for cytopathic effect (CPE). The original specimens were frozen at −70° C until final reports were issued. Culture tubes with CPE were tested by the Dupont Herpchek enzyme immuno assay (EIA) to confirm the presence of herpes simplex virus (HSV). (3,4) 170 OB patient specimens were positive by culture and confirmed by EIA.There were also 63 cultures exhibiting CPE ressembling HSV which were negative by EIA testing, which failed to pass in fresh tissue culture cells or progress to more enhanced CPE in culture. These original specimens were screened by electron microscopy after direct ultracentrifugation employing the Beckman airfuge with the EM 90 rotor on to formvar carbon-coated 300 mesh copper grids and negatively stained with 2% PTA.

Role of herpes simplex virus type 1 (HSV-1) in the pathogenesis of peptic ulcer disease

2001 ◽  
Vol 120 (5) ◽  
pp. A136-A137
Author(s):  
K TSAMAKIDES ◽  
E PANOTOPOULOU ◽  
D DIMITROULOPOULOS ◽  
M CHRISTOPOULO ◽  
D XINOPOULOS ◽  
...  
Keyword(s):  
Peptic Ulcer ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Peptic Ulcer Disease ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Ulcer Disease ◽  
Simplex Virus
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