scholarly journals Decreased reactivation of a herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) mutant using the in vivo mouse UV-B model of induced reactivation

2015 ◽  
Vol 21 (5) ◽  
pp. 508-517 ◽  
Author(s):  
Lbachir BenMohamed ◽  
Nelson Osorio ◽  
Ruchi Srivastava ◽  
Arif A. Khan ◽  
Jennifer L. Simpson ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Simplex Virus ◽  
Hsv 1

scholarly journals Herpes Simplex Virus Type 1 Evades the Effects of Antibody and Complement In Vivo

2002 ◽  
Vol 76 (18) ◽  
pp. 9232-9241 ◽  
Author(s):  
John M. Lubinski ◽  
Ming Jiang ◽  
Lauren Hook ◽  
Yueh Chang ◽  
Chad Sarver ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Immune Evasion ◽  
Herpes Simplex Virus Type ◽  
Complement Components ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus type 1 (HSV-1) encodes a complement-interacting glycoprotein, gC, and an immunoglobulin G (IgG) Fc binding glycoprotein, gE, that mediate immune evasion by affecting multiple aspects of innate and acquired immunity, including interfering with complement components C1q, C3, C5, and properdin and blocking antibody-dependent cellular cytotoxicity. Previous studies evaluated the individual contributions of gC and gE to immune evasion. Experiments in a murine model that examines the combined effects of gC and gE immune evasion on pathogenesis are now reported. Virulence of wild-type HSV-1 is compared with mutant viruses defective in gC-mediated C3 binding, gE-mediated IgG Fc binding, or both immune evasion activities. Eliminating both activities greatly increased susceptibility of HSV-1 to antibody and complement neutralization in vitro and markedly reduced virulence in vivo as measured by disease scores, virus titers, and mortality. Studies with C3 knockout mice indicated that other activities attributed to these glycoproteins, such as gC-mediated virus attachment to heparan sulfate or gE-mediated cell-to-cell spread, do not account for the reduced virulence of mutant viruses. The results support the importance of gC and gE immune evasion in vivo and suggest potential new targets for prevention and treatment of HSV disease.

scholarly journals Antiviral effect of oryzacystatin, a proteinase inhibitor in rice, against herpes simplex virus type 1 in vitro and in vivo.

1995 ◽  
Vol 39 (4) ◽  
pp. 846-849 ◽  
Author(s):  
H Aoki ◽  
T Akaike ◽  
K Abe ◽  
M Kuroda ◽  
S Arai ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Rice Seed ◽  
Simplex Virus ◽  
Hsv 1

Oryzacystatin (OC) is the first-described cystatin originating from rice seed; it consists of two molecular species, OC-I and OC-II, which have antiviral action against poliovirus in vitro (H. Kondo, S. Ijiri, K. Abe, H. Maeda, and S. Arai, FEBS Lett. 299:48-50, 1992). In the experiments reported here, we investigated the effects of OC-I and OC-II on the replication of herpes simplex virus type 1 (HSV-1) in vitro and in vivo. HSV-1 was inoculated onto monolayers of monkey kidney epithelial cells (CV-1 cells) at a multiplicity of infection of 0.1 PFU per cell. After adsorption of the virus onto cells, the cultures were incubated in the presence of either OC-I or OC-II in the concentration range of 1.0 to 300 microM, and the supernatant virus yield was quantitated at 24 h. The effective concentration for 90% inhibition of HSV-1 was 14.8 microM, while a cytotoxic effect on CV-1 cells without infection of HSV-1 was not observed below 500 microM OC-I. Therefore, the apparent in vitro chemotherapeutic index was estimated to be more than 33. In the mouse model of HSV-1-induced keratitis and encephalopathy, topical administration of OC-I to the mouse cornea produced a significant decrease in virus production in the cornea (mean virus yields: 3.11 log10 PFU in the treated group and 4.37 log10 PFU in the control group) and significant improvement in survival rates (P = 0.01). The in vivo antiherpetic effect of OC-I was comparable to that of acyclovir, indicating that topical treatment of HSV-1 infection in humans with OC-I might be possible. Our data also suggest the importance of some thiol proteinases, which may be derived from either the host's cells or HSV-1, during the replication process of HSV-1.

scholarly journals In Vivo Ablation of CD11c-Positive Dendritic Cells Increases Susceptibility to Herpes Simplex Virus Type 1 Infection and Diminishes NK and T-Cell Responses

2006 ◽  
Vol 80 (8) ◽  
pp. 3985-3993 ◽  
Author(s):  
Sadik H. Kassim ◽  
Naveen K. Rajasagi ◽  
Xiangyi Zhao ◽  
Robert Chervenak ◽  
Stephen R. Jennings
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The precise role of each of the seven individual CD11c+ dendritic cell subsets (DCs) identified to date in the response to viral infections is not known. DCs serve as critical links between the innate and adaptive immune responses against many pathogens, including herpes simplex virus type 1 (HSV-1). The role of DCs as mediators of resistance to HSV-1 infection was investigated using CD11c-diphtheria toxin (DT) receptor-green fluorescent protein transgenic mice, in which DCs can be transiently depleted in vivo by treatment with low doses of DT. We show that ablation of DCs led to enhanced susceptibility to HSV-1 infection in the highly resistant C57BL/6 mouse strain. Specifically, we showed that the depletion of DCs led to increased viral spread into the nervous system, resulting in an increased rate of morbidity and mortality. Furthermore, we showed that ablation of DCs impaired the optimal activation of NK cells and CD4+ and CD8+ T cells in response to HSV-1. These data demonstrated that DCs were essential not only in the optimal activation of the acquired T-cell response to HSV-1 but also that DCs were crucial for innate resistance to HSV-1 infection.

scholarly journals Sodium Butyrate: a Chemical Inducer of In Vivo Reactivation of Herpes Simplex Virus Type 1 in the Ocular Mouse Model

2007 ◽  
Vol 81 (11) ◽  
pp. 6106-6110 ◽  
Author(s):  
Donna M. Neumann ◽  
Partha S. Bhattacharjee ◽  
James M. Hill
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Sodium Butyrate ◽  
Herpes Simplex Virus Type ◽  
Early Time ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Recent studies have explored the chromatin structures associated with the herpes simplex virus type 1 (HSV-1) genome during latency, particularly with regard to specific histone tail modifications such as acetylation and dimethylation. The objective of our present study was to develop a rapid systemic method of in vivo HSV-1 reactivation to further explore the changes that occur in the chromatin structures associated with HSV-1 at early time points after the initiation of HSV reactivation. We present a uniform, rapid, and reliable method of in vivo HSV-1 reactivation in mice that yields high reactivation frequencies (75 to 100%) by using sodium butyrate, a histone deacetylase inhibitor, and demonstrate that the reactivating virus can be detected at the original site of infection.

scholarly journals Evaluation of a peptidomimetic ribonucleotide reductase inhibitor with a murine model of herpes simplex virus type 1 ocular disease.

1996 ◽  
Vol 40 (5) ◽  
pp. 1078-1084 ◽  
Author(s):  
C R Brandt ◽  
B Spencer ◽  
P Imesch ◽  
M Garneau ◽  
R Déziel
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Ribonucleotide Reductase ◽  
Herpes Simplex Virus Type ◽  
Ocular Infection ◽  
Simplex Virus ◽  
Hsv 1

The ribonucleotide reductase (RR) of herpes simplex virus type 1 (HSV-1) is an important virulence factor, being required for neurovirulence, ocular virulence, and reactivation from latency. The RR activity requires the association of two distinct homodimeric subunits, and the association of the subunits is inhibited in the presence of a peptide homologous to the carboxy terminus of the small subunit. A structural analog of the inhibitory peptide (BILD 1263) has been shown to inhibit the replication of HSV-1 at micromolar concentrations in vitro. We used a mouse model of HSV-1 ocular infection to determine the in vivo efficacy of topical BILD 1263. Treatment of HSV-1 KOS-infected mice resulted in significant reductions in the severity and incidence of stromal keratitis and corneal neovascularization. At higher concentrations (5%) BILD 1263 reduced the severity but not the incidence of blepharitis. Treatment with 5% BILD 1263 also reduced viral shedding from the cornea by 10- to 14-fold (P < 0.001). In uninfected mice treated with 5% BILD 1263, we found no evidence of corneal epithelial damage, conjunctivitis, or blepharitis, and histopathological studies revealed no changes in the corneas of these mice. These results show that the peptidomimetic RR inhibitor BILD 1263 is effective in preventing disease, has an antiviral effect in vivo, and has little or no toxicity.

scholarly journals The UL12.5 Gene Product of Herpes Simplex Virus Type 1 Exhibits Nuclease and Strand Exchange Activities but Does Not Localize to the Nucleus

2004 ◽  
Vol 78 (9) ◽  
pp. 4599-4608 ◽  
Author(s):  
Nina Bacher Reuven ◽  
Susumu Antoku ◽  
Sandra K. Weller
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Intracellular Localization ◽  
Strand Exchange ◽  
Null Mutant ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The herpes simplex virus type 1 (HSV-1) alkaline nuclease, encoded by the UL12 gene, plays an important role in HSV-1 replication, as a null mutant of UL12 displays a severe growth defect. Although the precise in vivo role of UL12 has not yet been determined, several in vitro activities have been identified for the protein, including endo- and exonuclease activities, interaction with the HSV-1 single-stranded DNA binding protein ICP8, and an ability to promote strand exchange in conjunction with ICP8. In this study, we examined a naturally occurring N-terminally truncated version of UL12 called UL12.5. Previous studies showing that UL12.5 exhibits nuclease activity but is unable to complement a UL12 null virus posed a dilemma and suggested that UL12.5 may lack a critical activity possessed by the full-length protein, UL12. We constructed a recombinant baculovirus capable of expressing UL12.5 and purified soluble UL12.5 from infected insect cells. The purified UL12.5 exhibited both endo- and exonuclease activities but was less active than UL12. Like UL12, UL12.5 could mediate strand exchange with ICP8 and could also be coimmunoprecipitated with ICP8. The primary difference between the two proteins was in their intracellular localization, with UL12 localizing to the nucleus and UL12.5 remaining in the cytoplasm. We mapped a nuclear localization signal to the N terminus of UL12, the domain absent from UL12.5. In addition, when UL12.5 was overexpressed so that some of the enzyme leaked into the nucleus, it was able to partially complement the UL12 null mutant.

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