scholarly journals Excoecarianin, Isolated fromPhyllanthus urinariaLinnea, Inhibits Herpes Simplex Virus Type 2 Infection through Inactivation of Viral Particles

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Hua-Yew Cheng ◽  
Chien-Min Yang ◽  
Ta-Chen Lin ◽  
Liang-Tzung Lin ◽  
Lien-Chai Chiang ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Viral Entry ◽  
Herpes Simplex Virus Type ◽  
Antiviral Effect ◽  
Vero Cells ◽  
Simplex Virus ◽  
Hsv 1

Phyllanthus urinariaLinnea (Euphorbiaceae) is one of the traditional medicinal plants widely used by oriental people to treat various diseases. We have previously demonstrated that the acetone extract ofP. urinariainhibits herpes simplex virus type 2 (HSV-2) but not HSV-1 infection. In a continuing effort to clarify the antiviral mechanisms ofP. urinaria, we isolated the pure compound excoecarianin from the whole plant ofP. urinariathrough acetone extraction, and investigated its anti-HSV-1 and HSV-2 activities. Our results indicated that excoecarianin protected Vero cells from HSV-2 but not HSV-1 infection, and its 50% inhibitory concentration (IC50) was 1.4 ± 0.1 μM. The antiviral effective concentration of excoecarianin did not affect the viability or the morphology of Vero cells. Although excoecarianin inhibited HSV-2 infection, the inhibitory effect, however, was most prominent when excoecarianin was concurrently added with the virus. Pretreatment of Vero cells with excoecarianin with removal of the drug prior to infection did not yield any antiviral effects, and the same observation was made for post viral entry treatment. Subsequent studies revealed that excoecarianin inactivated HSV-2 virus particles to prevent viral infection. A synergistic antiviral effect against HSV-2 was also observed when Vero cells were treated with a combination of acyclovir (ACV) and excoecarianin. These results suggested that excoecarianin merits to be further explored as an entry inhibitor against HSV-2 and could potentially be investigated for combinatorial drug treatment with nucleoside analogues such as ACV in therapeutic management of HSV-2 infection.

scholarly journals Multiple Peptides Homologous to Herpes Simplex Virus Type 1 Glycoprotein B Inhibit Viral Infection

2008 ◽  
Vol 53 (3) ◽  
pp. 987-996 ◽  
Author(s):  
Radeekorn Akkarawongsa ◽  
Nina E. Pocaro ◽  
Gary Case ◽  
Aaron W. Kolb ◽  
Curtis R. Brandt
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Viral Entry ◽  
Herpes Simplex Virus Type ◽  
Glycoprotein B ◽  
Induced Mutations ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The 773-residue ectodomain of the herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) has been resistant to the use of mutagenic strategies because the majority of the induced mutations result in defective proteins. As an alternative strategy for the identification of functionally important regions and novel inhibitors of infection, we prepared a library of overlapping peptides homologous to the ectodomain of gB and screened for the ability of the peptides to block infection. Seven of 138 15-mer peptides inhibited infection by more than 50% at a concentration of 100 μM. Three peptides (gB94, gB122, and gB131) with 50% effective concentrations (EC50s) below 20 μM were selected for further studies. The gB131 peptide (residues 681 to 695 in HSV-1 gB [gB-1]) was a specific entry inhibitor (EC50, ∼12 μM). The gB122 peptide (residues 636 to 650 in gB-1) blocked viral entry (EC50, ∼18 μM), protected cells from infection (EC50, ∼72 μM), and inactivated virions in solution (EC50, ∼138 μM). We were unable to discern the step or steps inhibited by the gB94 peptide, which is homologous to residues 496 to 510 in gB-1. Substitution of a tyrosine in the gB122 peptide (Y640 in full-length gB-1) reduced the antiviral activity eightfold, suggesting that this residue is critical for inhibition. This peptide-based strategy could lead to the identification of functionally important regions of gB or other membrane proteins and identify novel inhibitors of HSV-1 entry.

scholarly journals Microtubule Reorganization during Herpes Simplex Virus Type 1 Infection Facilitates the Nuclear Localization of VP22, a Major Virion Tegument Protein

2001 ◽  
Vol 75 (18) ◽  
pp. 8697-8711 ◽  
Author(s):  
Anna Kotsakis ◽  
Lisa E. Pomeranz ◽  
Amanda Blouin ◽  
John A. Blaho
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Nuclear Localization ◽  
Herpes Simplex Virus Type ◽  
Vero Cells ◽  
Productive Infection ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Full-length VP22 is necessary for efficient spread of herpes simplex virus type 1 (HSV-1) from cell to cell during the course of productive infection. VP22 is a virion phosphoprotein, and its nuclear localization initiates between 5 and 7 h postinfection (hpi) during the course of synchronized infection. The goal of this study was to determine which features of HSV-1 infection function to regulate the translocation of VP22 into the nucleus. We report the following. (i) HSV-1(F)-induced microtubule rearrangement occurred in infected Vero cells by 13 hpi and was characterized by the loss of obvious microtubule organizing centers (MtOCs). Reformed MtOCs were detected at 25 hpi. (ii) VP22 was observed in the cytoplasm of cells prior to microtubule rearrangement and localized in the nucleus following the process. (iii) Stabilization of microtubules by the addition of taxol increased the accumulation of VP22 in the cytoplasm either during infection or in cells expressing VP22 in the absence of other viral proteins. (iv) While VP22 localized to the nuclei of cells treated with the microtubule depolymerizing agent nocodazole, either taxol or nocodazole treatment prevented optimal HSV-1(F) replication in Vero cells. (v) VP22 migration to the nucleus occurred in the presence of phosphonoacetic acid, indicating that viral DNA and true late protein synthesis were not required for its translocation. Based on these results, we conclude that (iv) microtubule reorganization during HSV-1 infection facilitates the nuclear localization of VP22.

scholarly journals CD4+ T-cell responses to herpes simplex virus type 2 (HSV-2) glycoprotein G are type specific and differ in symptomatic and asymptomatic HSV-2-infected individuals

2004 ◽  
Vol 85 (8) ◽  
pp. 2139-2147 ◽  
Author(s):  
Kristina Eriksson ◽  
Lars Bellner ◽  
Staffan Görander ◽  
Gun-Britt Löwhagen ◽  
Petra Tunbäck ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Mononuclear Cells ◽  
Glycoprotein G ◽  
Simplex Virus ◽  
Hsv 1

T-cell recognition of the secreted and membrane-bound portions of the herpes simplex virus type 2 (HSV-2) glycoprotein G (sgG-2 and mgG-2, respectively) was compared in symptomatic and asymptomatic HSV-2-infected individuals and in HSV-2-seronegative controls and the responses with HSV-1 glycoproteins C and E (gC-1 and gE-1) were compared. CD4+ T cells from HSV-2-infected individuals specifically recognized both sgG-2 and mgG-2, whereas HSV-1-infected and HSV-seronegative controls did not respond to these glycoproteins. The responses to gC-1 and gE-1, on the other hand, were not type specific, as blood mononuclear cells from both HSV-1- and HSV-2-infected individuals responded in vitro. There was an association between the status of the infection (symptomatic versus asymptomatic) and the CD4+ T-cell responsiveness. Symptomatic HSV-2-seropositive individuals responded with significantly lower Th1 cytokine production to sgG-2 and mgG-2 than did asymptomatic HSV-2-infected carriers, especially within the HSV-1-negative cohort. No differences in T-cell proliferation were observed between asymptomatic and symptomatic individuals. The results have implications for studies of HSV-2-specific CD4+ T-cell reactivity in general and for analysis of immunological differences between asymptomatic and symptomatic individuals in particular.

Inability to rescue viral genes from human cells biochemically transformed by herpes simplex virus type 2 DNA

1981 ◽  
Vol 27 (10) ◽  
pp. 1123-1128 ◽  
Author(s):  
José Campione-Piccardo ◽  
William E. Rawls
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Human Cells ◽  
Viral Genes ◽  
Simplex Virus ◽  
Hsv 1

Thymidine kinase negative (TK−) mutants of HSV-1 were used to attempt to rescue HSV-2 genes from cells biochemically transformed with HSV-2 DNA. The results indicate that the occurrence of a rescue event was less than 7 × 10−7 in this system.

scholarly journals Nucleolar localization of the UL3 protein of herpes simplex virus type 2

1999 ◽  
Vol 80 (8) ◽  
pp. 2157-2164 ◽  
Author(s):  
Hiroshi Yamada ◽  
Yue-Mei Jiang ◽  
Hong-Yan Zhu ◽  
Kyoko Inagaki-Ohara ◽  
Yukihiro Nishiyama
Keyword(s):  
Amino Acids ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Fusion Protein ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Vero Cells ◽  
Nucleolar Localization ◽  
Simplex Virus

A rabbit polyclonal antiserum was raised against a recombinant 6×His–UL3 fusion protein expressed in Escherichia coli and used to examine the intracellular localization of the UL3 protein of herpes simplex virus type 2 (HSV-2). The antiserum reacted specifically with 31 and 34 kDa proteins in HSV-2 186-infected Vero cells and with 31 and 35 kDa proteins in UL3-expressing COS-7 cells. The UL3 protein localized both in the cytoplasm and in five to ten bright fluorescent granules in the nucleus close to the nuclear membrane at 4 h post-infection (p.i.). These structures became bigger at 5 h p.i. and showed doughnut-like forms at 6 h p.i. In transfected Vero cells, the UL3 protein localized exclusively in the nucleoplasm and specifically in the nucleolus. Five deletion mutants of the UL3 protein were constructed for transfection assays and the results showed that the region containing amino acids 100–164 was important for nucleolar localization. Moreover, green fluorescent protein (GFP)-targetting experiments showed that the region containing amino acids 100–164 was able to transport non-nucleolar GFP to the nucleolus as a fusion protein.

scholarly journals Herpes Simplex Virus Type 2 Is More Difficult to Neutralize by Antibodies Than Herpes Simplex Virus Type 1

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 478
Author(s):  
Christiane Silke Heilingloh ◽  
Christopher Lull ◽  
Elissa Kleiser ◽  
Mira Alt ◽  
Leonie Schipper ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Vaccine Trial ◽  
Antibody Treatment ◽  
Simplex Virus ◽  
Hsv 1

Infections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are a global health burden. Besides painful oral or genital lesions in otherwise healthy subjects, both viruses can cause devastating morbidity and mortality in immune-compromised and immune-immature individuals. The latter are particularly susceptible to a disseminated, life-threatening disease. Neutralizing antibodies (NAb) constitute a correlate of protection from disease, and are promising candidates for the prophylactic or therapeutic treatment of severe HSV infections. However, a clinical vaccine trial suggested that HSV-2 might be more resistant to NAbs than HSV-1. In the present study, we investigated the antiviral efficacy of the well-characterized humanized monoclonal antibody (mAb) hu2c against HSV-2, in a NOD/SCID immunodeficiency mouse model. Despite the fact that hu2c recognizes a fully conserved epitope and binds HSV-1 and HSV-2 glycoprotein B with equal affinity, it was much less effective against HSV-2 in vitro and in NOD/SCID mice. Although intravenous antibody treatment prolonged the survival of HSV-2-infected mice, complete protection from death was not achieved. Our data demonstrate that HSV-2 is more resistant to NAbs than HSV-1, even if the same antibody and antigen are concerned, making the development of a vaccine or therapeutic antibodies more challenging.

scholarly journals Herpes Simplex Virus Type 1 and Type 2 Infection Increases Atherosclerosis Risk: Evidence Based on a Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Yu peng Wu ◽  
Dan dan Sun ◽  
Yun Wang ◽  
Wen Liu ◽  
Jun Yang
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Simplex Virus ◽  
Hsv 1

Objective.The aim of our study was to evaluate the relation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infection with the risk of atherosclerosis (AS).Methods.A systematic literature search was performed through three electronic databases. The pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were used to assess the effect of HSV-1 and HSV-2 infection on AS risk.Results.17 studies were available for meta-analysis of HSV-1 infection and AS risk and seven studies for meta-analysis of HSV-2 infection and AS risk. Subjects exposed to HSV-1 infection exhibited an increased risk of AS (OR = 1.77; 95% CI: 1.40–2.23;P<0.001). And consistent elevated AS risks for HSV-1 positive subjects were found in all subgroup analysis of disease type, region, male proportion, and age. HSV-2 positive subjects demonstrated significantly increased AS risk (OR = 1.37; 95% CI: 1.13–1.67;P<0.005). In subgroup analysis, elevated AS risks were only observed in myocardial ischemia group, male proportion >60% group, and age ≤60-year-old group.Conclusion.Our meta-analysis indicated that HSV-1 and HSV-2 infection could increase the risk of contracting AS.

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