Interleukin 1βreceptor and synaptic dysfunction in recurrent brain infection with Herpes simplex virus type-1

Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.

A Meta-Analysis on the Correlation Between Herpes Simplex Virus Type II Infection and Adverse Pregnancy Outcomes in China

Objective:To systematically evaluate the relationship between herpes simplex virus type II(HSV-2)infection in pregnant women and the adverse pregnancy outcomes(preterm delivery,spontaneous abortion,stillbirth,monstrum,low birth weight,intrauterine growth retardation,premature rupture of membranes),so as to provide clinical guidance for the prevention and treatment of adverse pregnancy outcomes caused by HSV-2 infection in pregnant women.Methods:2140 articles were collected from PubMed,China National Knowledge Infrastructure(CNKI),and other databases for the past 20 years.According to the inclusion criteria,the literatures about the relationship between HSV-2 infection of pregnant women and adverse pregnancy outcomes were screened.The effect model was determined by heterogeneity test results,and the meta-analysis was carried out by RevMan 5.3 software.Results:The results of meta-analysis showed that the positive rate of HSV-2 was higher in the adverse pregnancy group than in the control group(odds ratio[OR]:7.92,95%confidence interval[Cl]:3.91-16.01),and the difference was statistically significant.Conclusion:HSV-2 infection will increase the risk of adverse pregnancy outcomes.Prevention and effective control of HSV-2 infection in early pregnancy can reduce the rate of adverse pregnancy outcome,which is of great significance to the promotion of eugenics.

The Herpes Simplex Virus Type 1 Multiple Function Protein ICP27

The herpes simplex virus type 1 （HSV-1） infected-cell protein 27 （ICP27） is an essential, highly conserved protein involved in various steps of HSV-1 gene regulation as well as in the shut-off of host gene expression during infection. It functions primarily at the post-transcriptional level in inhibiting precursor mRNA splicing and in promoting nuclear export of viral transcripts. Recently, many novel functions performed by the HSV- 1 ICP27 protein were shown, including leptomycin B resistance, inhibition of the type I interferon signaling, regulation of the viral mRNA translation and determining the composition of HSV-1 virions

Feasibility of herpes simplex virus type 1 mutants labeled with radionuclides for tumor treatment

For over one hundred years, viruses have been recognized as capable of killing tumor cells. At present, people are still researching and constructing more suitable oncolytic viruses for treating different malignant tumors. Although extensive studies have demonstrated that herpes simplex virus type 1 (HSV-1) is the most potential oncolytic virus, therapies based on herpes simplex virus type 1 vectors still arouse bio-safety and risk management issues. Researchers have therefore introduced the new idea of treating cancer with HSV-1 mutants labeled with radionuclides, combining radionuclide and oncolytic virus therapies. This overview briefly summarizes the status and mechanisms by which oncolytic viruses kill tumor cells, discusses the application of HSV-1 and HSV-1 derived vectors for tumor therapy, and demonstrates the feasibility and prospect of HSV-1 mutants labeled with radionuclides for treating tumors.

A functional type I interferon pathway drives resistance to cornea herpes simplex virus type 1 infection by recruitment of leukocytes

Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 （HSV-1） infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-a. We also report mice deficient in the A1 chain of the type I IFN receptor （CDl18-/） are extremely sensitive to ocular infection with low doses （100 PFU） of HSV-1 as seen by significantly elevated viral titers in the cornea Compared to wild type （WT） controls. The enhanced susceptibil- ity correlated with a loss of CD4＋ and CD8＋ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CDll8/ mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking.

Antiviral activity of Basidiomycete mycelia against influenza type A(serotype H1N1) and herpes simplex virus type 2 in cell culture

In this study, we investigated the in vitro antiviral activity of the mycelia of higher mushrooms against influenza virus type A(serotype H1N1) and herpes simplex virus type 2(HSV-2), strain BH. All 10 investigated mushroom species inhibited the reproduction of influenza virus strain A/FM/1/47(H1N1) in MDCK cells reducing the infectious titer by 2.0–6.0 lg ID50. Four species, Pleurotus ostreatus, Fomes fomentarius, Auriporia aurea, and Trametes versicolor, were also determined to be effective against HSV-2 strain BH in RK-13 cells, with similar levels of inhibition as for influenza. For some of the investigated mushroom species—Pleurotus eryngii, Lyophyllum shimeji, and Flammulina velutipes—this is the first report of an anti-influenza effect. This study also reports the first data on the medicinal properties of A. aurea, including anti-influenza and antiherpetic activities. T. versicolor 353 mycelium was found to have a high therapeutic index(324.67), and may be a promising material for the pharmaceutical industry as an anti-influenza and antiherpetic agent with low toxicity. Mycelia with antiviral activity were obtained in our investigation by bioconversion of agricultural wastes(amaranth flour after CO2 extraction), which would reduce the cost of the final product and solve some ecological problems.

The Herpes Simplex Virus Type 1 Infected Cell Protein 22

As one of the immediate-early(IE)proteins of herpes simplex virus type 1(HSV-1),ICP22 is a multifunctional viral regulator that localizes in the nucleus of infected cells.It is required in experimental animal systems and some nonhuman cell lines,but not in Vero or HEp-2 cells.ICP22 is extensively phosphorylated by viral and cellular kinases and nucleotidylylated by casein kinase Ⅱ.It has been shown to be required for efficient expression of early(E)genes and a subset of late(L)genes.ICP22,in conjunction with the UL13 kinase,mediates the phosphorylation of RNA polymerase Ⅱ.Both ICP22 and UL13 are required for the activation of cdc2,the degradation of cyclins A and B and the acquisition of a new cdc2 partner,the UL42 DNA polymerase processivity factor.The cdc2-UL42 complex mediates postranscriptional modification of topoisomerase Ⅱα in an ICP22-dependent manner to promote L gene expression.In addition,ICP22 interacts with cdk9 in a Us3 kinase dependent fashion to phosphorylate RNA polymerase Ⅱ.

Herpes simplex virus type 1 in peptic ulcer disease: An inverse association with Helicobacter pylori

AIM： To assess the frequency of herpes simplex virus type I in upper gastrointestinal tract ulcers and normal mucosa with the modern and better assays and also with a larger number of well characterized patients and controls and its relationship to Helicobacter pylori（H pylori）. METHODS： Biopsy specimens from 90 patients （34 with gastric ulcer of the prepyloric area and 56 with duodenal ulcer） were evaluated. Biopsies from 50 patients with endoscopically healthy mucosa were considered as the control group. The method used to identify herpes simplex virus-1 （HSV-1） was polymerase chain reaction. Hpylori was detected by the CLO-test and by histological method. RESULTS： Herpes simplex virus-1 was detected in 28 of 90 patients with peptic ulcer （31%） Ⅲ of 34 patients with gastric ulcer （32.4%） and 17 of 56 with duodenal ulcer （30.4%）1 exclusively close to the ulcerous lesion. All control group samples were negative for HSV-1. The likelihood of Hpylori negativity among peptic ulcer patients was significantly higher in HSV-1 positive cases than in HSV-1 negative cases （P = 0.009）. Gastric ulcer patients with HSV-1 positivity were strongly associated with an increased possibility of Helicobacter pylori negativity compared to duodenal ulcer patients （P = 0.010）. CONCLUSION： HSV-1 is frequent in upper gastrointestinal tract ulcers but not in normal gastric andduodenal mucosa. There is an inverse association between HSV-1 and Hpylori infection.

SEARCH FOR HERPES SIMPLEX VIRUS TYPE2（HSV－2）AND HUMAN PAPILLOMAVIRUS（HPV）IN THE NORMAL AND ABNORMAL CERVICAL SAMPLES

The specimens of 111 cervical carcinomas. 68 chronic cervicitis and 43 normal cervical exfoliated epithelial cells were examined for the presence of HSV2 DNA sequences with DNA hybridization using HSV2 BgL Ⅱ N fragment probe labelled by 32PdCTP. The result showed that the infection rates of HSV2 in the samples of cervical cancer.chronic cervicitis and normal epithelial cells were 1 4. 41 %(16/111). 27.94%( 19/68) and 25.58% ( 11/43),respectively. It was implied that early stages carcinogenesis of cervical epithelial cells might be correlated with the HSV2 infection.Sixteen HSV 2 positive samples of cervical carcinomas were also examined for the presence of the sequences homologous to human papillomavirus (HPV) type 6B/11. 16 and 18 DNA using dot blot hybridization (Tm17℃). The result indicated that 13 out of 16 were HPV 16 DNA hybridization positive accounting for 81. 2% of all HSV-2 positive samples and none of them were positive for HPV type 6B/11 and 18. The result indicated that double infection of HSV 2 and HPV16 in the same cervical carcinoma tissues may provide a strong evidence of the viral synergistic interaction in the induction of female cervical

A Multiple Functional Protein:the Herpes Simplex Virus Type 1 Tegument Protein VP22

The herpes simplex virus type 1 （HSV-1） VP22, is one of the most abundant HSV-I tegument proteins with an average stoichiometry of 2 400 copies per virion and conserved among alphaherpesvirinae. Many functions are attributed to VP22, including nuclear localization, chromatin binding, microtubule binding, induction ofmicrotubule reorganization, intercellular transport, interaction with cellular proteins, such as template activating VP16, pU factor I （TAF-I） and nonmuscle myosin II A （NMIIA）, and viral proteins including pUS9 and pUL46, glycoprotein E （gE） and gD. Recently, many novel functions perform tegument protein ed by the HSV-1 VP22 protein have been shown, including promotion of protein synthesis at late times in infection, accumulation of a subset of viral mRNAs at early times in infection and possible transcriptional regulation function .

Herpes Simplex Virus Type 1 ICP27 Protein:Its Expression, Purification and Specific Antiserum Production

Herpes simplex virus type 1 (HSV-1) is the causative agent of cold sores and other more serious diseases. HSV-1 infected-cell protein 27 (ICP27) is an immediate-early regulatory phosphoprotein homologous to gene products identified in all classes of herpesviruses so far. To raise the antiserum to ICP27 for further characterization of its biological function, the ICP27 gene was cloned into the pET-28a (+) vector, then ICP27 protein was expressed in E. coli and purified by nickel-nitrilotriacetic acid (Ni 2+ -NTA) affinity resin column, finally the purified protein was used to raise antiserum. Western blot analysis demonstrated that the antiserum recognized the recombinant protein, and the antiserum was able to probe the ICP27 in HSV-1 infected cells with high specificity by immunofluorescence assay (IFA). Therefore, the specific antiserum will provide a valuable tool for further studies investigating ICP27's biological function during HSV-1 infection.

Oral and perioral herpes simplex virus infection type I in a fivemonth- old infant: A case report

BACKGROUND Herpes simplex virus(HSV)is a highly infectious pathogen that is easily transmitted via the bodily fluids of an infected individual.This virus usually affects individuals older than six months of age,and rarely causes lesions or symptoms in younger patients.CASE SUMMARY We present the case of a five-month-old healthy girl who presented with painful herpetic gingivostomatitis and perioral vesicles.We discuss the pathophysiology of primary HSV infection and the effect of maternal antibodies on the infant’s immune system.In addition,we explain the diagnosis,management,and prognosis of HSV infection in young infants.CONCLUSION This case highlights the importance of early diagnosis and management of HSV infections to decrease the risk of developing severe complications and death.

FAILURE OF HERPES SIMPLEX VIRUS TYPE 2 TO SUBSTITUTE FOR DIMETHYL-BENZANTHRACENE IN TWO-STAGE SKIN CARCINOGENESIS

There are some Indications thtt herpes aimplex virus (HSV) may be mutagenic. Specific chromosomal changes have also been demonstrated In cultured cells infected with HSV. To further Investigate the mutagenic activity of HSV type 2 (HSV-2) we used mouse skin as a model system for cardnogenetls. Inoculation of the back skin of 4-week-old Sencar mke with live virus twice per week for one week or with Inactivated virus twice per week for two weeks was used to Initiate the mouse akin. After Initiation with HSV-2, 12-O-tetradecanoylphorbol-13-acetale(TPA) was applied twice weekly for 50 weeks as a promoter. During a period of 52 weeks, no skin carcinoma was found In the experimental groups, whereas 55% of control mice treated with 9, 10-dlmethy1-1, 2- benzanthracene (DMBA ) and then with TPA-developed skin carcinoma. The results demonstrate that HSV-2 could not substitute for DMBA in this animal model of two-stage skin carcinogenesis.

Preliminary study on Herpes simplex virus type 1 infection of human oral epithelial cell in vitro

Objective： To explore the functions and mechanisms of herpes simplex virus type I（HSV-1） while infecting human oral epithelial cells in vitro（being similar to the infection in vivo）. Methods：An abundance of HSV-1 strains amplified in Vero cells were used to infect human oral epithelial cells. The culture supernatant was collected to infect Vero cells again. Morphology of HSV-1 was identified by inverted microscope and transmission electron microscope. Nucleic acid of the virus was detected by PCR. Results：The infected human oral epithelial cells didn＇ t display an obvious cytopathic effect（CPE） under inverted microscope（while Vero cells which were infected by the culture supernatant showed typical（CPE）. The virus particles were not observed in the cytoplasm nor in nucleus of human oral epithelial cells, however under transmission electron microscope in the cytoplasm of Vero cells, the nucleic acid of HSV-1 could be detected in infected human oral epithelial cells, by PCR. Conclusion-HSV-1 can successfully infect human oral epithelial cells. This model may provide a useful approach for studying the pathogenesis of herpes virus-associated periodontal disease.

Consistency Analysis of Detection Results of Two Herpes Simplex Virus (HSV) Type II Nucleic Acid Detection Kits

Objective: The objective of the study is to verify the clinical validity of the following kits with the comparative experimental analysis and evaluate whether their performance can meet the clinical requirements, i.e. Class III in vitro diagnostic reagent “Herpes Simplex Virus (HSV) Type II Nucleic Acid Detection Kit (PCR-Fluorescence Probe Method)” of Daan Gene Co., Ltd. (Daan kit for short) and “Herpes Simplex Virus (HSV) Type II Nucleic Acid Detection Kit (Fluorescence PCR Method)” of Wuhan Biot Gene Co., Ltd. (Biot kit for short). Method: In the study process, the samples were divided into positive and negative groups according to the control test results, and the clinical application performance of Daan kit and Biot kit was evaluated by comparing their test results. Results: The results show that two kits indicate the same test results, i.e. 26 positive and 107 negative samples in a total of 133 male urethral discharge samples, and 32 positive and 238 negative samples in a total of 270 female cervical secretion samples. Conclusion: It can be concluded from the clinical test that Daan and Biot Herpes Simplex Virus (HSV) Type II Nuc- leic Acid Test Kits are reliable, accurate, safe, convenient for use, stable and high-value in the clinical application.

APPROXIMATION BY INTEGRAL TYPE MEYER-KONIG-ZELLER OPERATORS ON A SIMPLEX

Letbe a simplex in The integral type Meyer-Komg-Zeller operators are constructed on the simplex T, and the degree of approximation of these operators for L'-functions is obtained.

Streptococcus pneumoniae and Herpes Simplex Virus-1 Central Nervous System Co-Infection

Co-infections of the central nervous system (CNS) caused by bacterial and viral pathogens are considered to be rare. Herpes simplex virus type-1 (HSV-1) reactivation following Streptococcus pneumoniae infection is well described but most cases are related to oral or cutaneous lesions or in respiratory samples. HSV-1 CNS reactivation after Streptococcus pneumoniae meningitis is a very rare event and may have significant morbidity and mortality. In this case report, we describe a 71-year-old female patient that presented with a history of abdominal pain and confusion/disorientation that had tonic-clonic seizures while in the Emergency Department. The diagnostic work-up confirmed CNS co-infection caused by Streptococcus pneumoniae and HSV-1. Of note, beyond age, the patient had no known risk factors for both entities and recovered fully after antibiotic and antiviral therapy. This case underlines that clinicians must be aware of CNS co-infection despite being a rare diagnosis. This should be suspected particularly in patients who present an unusual clinical course of CNS infection.

Effect of Gardenia extract ZG on the adsorption quantity of herpes simplex virus type 1 (HSV-1)

To observe the effect of Gardenia extract ZG on the adsorption quantity of herpes simplex virus type 1 （HSV-1） so as to explore the mechanism of its antiviral activity, fluorescein isothiocyanate （FITC） was used as the fluorescent probe to label viruses and heparin sodium was used as control. Meanwhile, the effect of Gardenia extract ZG on the adsorption quantity on the surface of Hep-2 cells was determined by flow cytometry. It was demonstrated that adsorption of HSV-1 on the surface of Hep-2 cells exhibited the character of saturation and specificity and heparin sodium could prevent attachment of viruses on these ceils. These results are in accord with those reported previously. It was also proved that the manner of drug-use prior to adsorption or simultaneous use of drug and adsorption was better than adsorption prior to drug-use, and the inhibition rates of the former and latter manner were 84.76% and 82.92% respectively. Three manners of drug-use with Gardenia extract ZG were all effective to reduce the adsorption quantity of viruses, especially the manner of simultaneous use of drug and adsorption with an adsorption inhibition rate of 68.46%. From the above observation, it is apparent that the mechanism of anti-viral activity of Gardenia extract ZG may be via several steps involved in the HSV-1 adsorption.

HSV1感染中的表观遗传调控机制研究进展

1型单纯疱疹病毒(HSV1)是一类最为常见的人类传染病原体,感染后可导致一系列程度不同的疾病。HSV1在中枢神经系统的潜伏感染及偶发重激活是其病理发生的关键,也为抗病毒治疗带来了巨大的挑战。目前,关于HSV1感染的建立、维持和重激活的机制并未完全阐明,但普遍认为表观遗传调控可能在其中扮演重要作用。越来越多研究表明,病毒裂解期和潜伏感染期的基因组呈现不同的染色质结构,其富含的多种翻译后修饰组蛋白赋予病毒基因转录激活或抑制特征。此外,病毒潜伏相关转录本LATs也可能参与基因组表观遗传修饰调控。

Anti-herpes simplex virus activities of monogalactosyl diglyceride and digalactosyl diglyceride from Clinacanthus nutans, a traditional Thai herbal medicine

Objective: To evaluate the monogalactosyl diglyceride(MGDG) and digalactosyl diglyceride(DGDG) from Clinacanthus nutans(C. nutans) for their in vitro antiviral activities against herpes simplex virus type 1(HSV-1) and type 2(HSV-2) by plaque reduction assay.Methods: MGDG and DGDG were extracted with chloroform from C. nutans leaves.MGDG and DGDG were separated from chloroform crude extract using column chromatography, characterized by thin layer chromatography and quantified by high performance liquid chromatography. The anti HSV-1 and 2 activity against pre-treatment and posttreatment of the compounds was evaluated using plaque reduction assay. The cytotoxicity of the extract and the compounds on Vero cells were performed by MTT assay.Results: MGDG and DGDG obtained by column chromatography showed identical profiles as standard MGDG and standard DGDG using thin layer chromatography and high performance liquid chromatography. MGDG and DGDG from C. nutans showed 100%inhibition of HSV-1 replication at the post step of infection at noncytotoxic concentration with IC50 values of 36.00 and 40.00 mg/m L, and HSV-2 at 41.00 and 43.20 mg/mL,respectively. Moreover, MGDG and DGDG from C. nutans were demonstrated to have antiherpes simplex activity at the same level as standard synthetic compounds. In contrast, pretreatment of Vero cells with MGDG and DGDG before HSV-1 and HSV-2 infection did not show inhibitory effect against these viruses. MGDG and DGDG exhibited antiviral activity against HSV-1 with selectivity index of 26.00 and 23.00 and HSV-2 of 23.30 and 21.30.Conclusions: MGDG and DGDG from C. nutans, a traditional Thai herbal medicine illustrated inhibitory activity against HSV-1 and HSV-2, probably by inhibiting the late stage of multiplication, suggesting their promising use as anti-HSV agents.