• IMMUNE NETWORK
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• v.12 no.5
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• pp.196-206
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• 2012

Besides their role as building blocks of protein, there are growing evidences that some amino acids have roles in regulating key metabolic pathways that are necessary for maintenance, growth, reproduction, and immunity. Here, we evaluated the modulatory functions of several amino acids in protective immunity against mucosal infection of herpes simplex virus type 1 (HSV-1). We found that glutamine (Gln) and leucine (Leu) showed enhanced protective immunity to HSV-1 mucosal infection when two administration of Gln and single administration of Leu per day, but not when administered in combinations. Ameliorated clinical signs of HSV-1 challenged mice by the intraperitoneal administration of Gln and Leu were closely associated with viral burden and IFN-${\gamma}$ production in the vaginal tract at 2 and 4 days post-infection. In addition, the enhanced production of vaginal IFN-${\gamma}$ appeared to be caused by NK and HSV-1 antigen-specific Th1-type CD4+ T cells recruited into vaginal tract of mice treated with Gln and Leu, which indicates that IFN-${\gamma}$, produced by NK and Th1-type CD4+ T cells, may be critical to control the outcome of diseases caused by HSV-1 mucosal infection. Collectively, our results indicate that intraperitoneal administration of Gln and Leu following HSV-1 mucosal infection could provide beneficial effects for the modulation of protective immunity, but dosage and frequency of administration should be carefully considered, because higher frequency and overdose of Gln and Leu, or their combined treatment, showed detrimental effects to protective immunity.

• Journal of Microbiology and Biotechnology
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• v.18 no.2
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• pp.350-354
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• 2008

In order to investigate the prevalence of sexually transmitted viruses such as human papillomavirus (HPV) and herpes simplex virus (HSV) in Korean commercial sex workers (CSWs), we selected 188 CSWs (age range 20-44 years, median age 24 years) who regularly visited one public health center in Seoul, Korea. HPV genotypes were analyzed by using a HPV DNA Chip, and an enzyme-linked immunosorbent assay (ELISA) was used to detect type-specific IgG against HSV2 antibody identifying seropositivity for HSV2 infection. Polymerase chain reaction (PCR) was performed with specific primers to detect HPV and HSV1/2 in cervical swabs from the CSWs. The prevalence of HPV infection was 83.5% in 188 cervical swab specimens and the main high-risk HPV genotypes were HPV16, 18, 56, and 58. The principal low-risk HPV genotypes were HPV6 and 11. The prevalence of HSV1/2 DNA was 13.8% and HSV2 seroprevalence was 86.2%. These results suggest that high frequencies of HPV and HSV2 infection might contribute to the rapid spread of STD viruses in CSWs in Korea. Additionally, an understanding of why high-risk HPV genotypes are so prevalent could provide guidelines for prophylactic vaccine development in Korea.

• Clinical and Experimental Pediatrics
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• v.46 no.9
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• pp.939-943
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• 2003

Neonatal herpes simplex virus(HSV) infections result in significant morbidity and mortality. Although acyclovir treatment has improved survival, severe neurological sequelae can occur in the majority of survivors. HSV infections limited to the skin, eyes and mouth(SEM) can cause neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. National Institutes of Allergy and Infectious Diseases(NIAID) Collaborative Antiviral Study Group conducted a phase I/II trial of continuous oral acyclovir therapy for the suppression of cutaneous recurrences. We describe a preterm infant who had two recurrences after neonatal SEM disease had been treated with intravenous acyclovir, and there were no more recurrences after continuous oral acyclovir suppressive therapy for six months. We report this case with a review of related literature.

• The Journal of Korean Society of Virology
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• v.28 no.3
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• pp.215-224
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• 1998

Cloning, sequencing and expressing in E. coli of the thymidine kinase (TK) gene of Herpes simplex virus type-1 (HSV-1) strain F was investigated. The TK gene, located in the BamHI 3.74 kb DNA fragment of the plasmid pHLA-12, was amplified by polymerase chain reaction (PCR). The 1,131 kb PCR product was cloned into the BamHI and EcoRI sites of pBacPAK9 plasmid and then named pBac-TK recombinant. The TK gene was subcloned into the BamHI and BglII sites of pQE-30, and named pQE-TK recombinant. The nucleotide sequence of the 1,131 kb TK gene was determined, and the GC content was 65.13%. There were deduced 367 amino acid residues with a total molecular weight of 43 kDa. The weight was confirmed by the protein produced by E. coli M15/pQE-TK on the SDS-PAGE and Western blot. The production of the TK protein in the IPTG induced cells was measured over 4 h. At the end of 1, 2 and 3 h the level increased by 146, 204 and 242%, respectively. The amount of the protein at the highest fraction purified with Ni-NTA resin chromatography was $0.68\;{\mu}g$ per ml. The soluble state TK protein was present in the cytoplasm. In these results the F strain was different in base sequence and amino acid sequence from that of the CL101 strain, which caused difference in their strains.

• Journal of Ginseng Research
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• v.37 no.2
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• pp.210-218
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• 2013

Numerous studies have suggested that Korean red ginseng (KRG) extract has various immune modulatory activities both in vivo and in vitro. In this study, we used a mouse model to examine the effects of orally administered KRG extract on immunity against herpes simplex virus (HSV). Balb/c mice were administered with 100, 200, and 400 mg/kg oral doses of KRG extract for 10 d and then vaginally infected with HSV. We found that KRG extract rendered recipients more resistant against HSV vaginal infection and further systemic infection, including decreased clinical severity, increased survival rate, and accelerated viral clearance. Such results appeared to be mediated by increased vaginal IFN-${\gamma}$ secretion. Moreover, increased mRNA expression of IFN-${\gamma}$, granzyme B, and Fas-ligand was identified in the iliac lymph node and vaginal tracts of KRG extract treated groups (200 and 400 mg/kg). These results suggest that the activities of local natural killer cells were promoted by KRG extract consumption and that KRG may be an attractive immune stimulator for helping hosts overcome HSV infection.

• Molecules and Cells
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• v.45 no.7
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• pp.479-494
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• 2022

Human mesenchymal stem cells (MSCs) are multipotent stem cells that have been intensively studied as therapeutic tools for a variety of disorders. To enhance the efficacy of MSCs, therapeutic genes are introduced using retroviral and lentiviral vectors. However, serious adverse events (SAEs) such as tumorigenesis can be induced by insertional mutagenesis. We generated lentiviral vectors encoding the wild-type herpes simplex virus thymidine kinase (HSV-TK) gene and a gene containing a point mutation that results in an alanine to histidine substitution at residue 168 (TK(A168H)) and transduced expression in MSCs (MSC-TK and MSC-TK(A168H)). Transduction of lentiviral vectors encoding the TK(A168H) mutant did not alter the proliferation capacity, mesodermal differentiation potential, or surface antigenicity of MSCs. The MSC-TK(A168H) cells were genetically stable, as shown by karyotyping. MSC-TK(A168H) responded to ganciclovir (GCV) with an half maximal inhibitory concentration (IC₅₀) value 10-fold less than that of MSC-TK. Because MSC-TK(A168H) cells were found to be non-tumorigenic, a U87-TK(A168H) subcutaneous tumor was used as a SAE-like condition and we evaluated the effect of valganciclovir (vGCV), an oral prodrug for GCV. U87-TK(A168H) tumors were more efficiently ablated by 200 mg/kg vGCV than U87-TK tumors. These results indicate that MSC-TK(A168H) cells appear to be pre-clinically safe for therapeutic use. We propose that genetic modification with HSV-TK(A168H) makes allogeneic MSC-based ex vivo therapy safer by eliminating transplanted cells during SAEs such as uncontrolled cell proliferation.

• Journal of Yeungnam Medical Science
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• v.4 no.2
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• pp.205-210
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• 1987

Kaposi's varicelliform eruption is a more or less generalized infection of the skin, and sometimes of internal organs, with herpes simplex, vaccinia or Coxsackie virus A 16 ; it appears in people who have atopic dermatitis or some other skin diseases. There is a predilection for infants and children, but no age-group is exempt. We reported 3 cases of Kaposi's varicelliform eruption with atopic dermatitis. They had characteristic multiple umbilicated vesicles on the sites that atopic dermatitis had been involved. A 14-year-old boy and a 2-month-old infant had fever. A 17-year-old boy had wide-spread vesicles. All three patients showed multinucleated giant cells on Tzanck test, that suggests herpes simplex virus origin. They were treated with acyclovir. Within 1 to 2 days after the initiation of the therapy, new lesions had ceased to develop. Most of the lesions were cleared in 7 days without complication.

• The Korean Journal of Cytopathology
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• v.1 no.1
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• pp.74-84
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• 1990

Herpes simplex virus type 1 and 2(HSV-1, HSV-2) are the ubiquitous human pathogens responsible for a variety of afflictions. HSV-2 is one of the viruses that were suspected of promoting carcinogenesis in the uterine cervix. Certainly, there is a need for the more sensitive and accurate laboratory techniques for HSV detection. We examined total 80 cases of smears including 17 Tzanck smears of skin and 63 cases of Papanicolaou smears from total 77 patients with clinical impression of herpetic infections, from September, 1985 through August, 1989. Immunohistochemical typings for HSV-1 and HSV-2 were performed together with routine cytologic findings and compared. The results are as follows : 1) Patients were 9 males and 33 females, and age distribution was between 5 and 71 years. 2) Subjective symptoms such as ulceration, vesicle, vaginal discharge, pruritus, and pain were complained in 36 patients and 38 cases were genital herpes. Recurrence was noted in 11 cases. 3) Positive results were obtained in 42 among 80 cases. 4) Both routine cytology and immunohistochemical staining were positive in 13 cases and in 24 cases only immunohistochemical staining were positive. 5 cases were positive only in routine cytologic smears. 5) The cases that immunocytochemical stain had been performed were 37 cases, which were all positive in type 2. Among the above 37 cases, type 1 also were positive in 5 cases. The results show that the immunoperoxidase technique is one of the rapid and reliable method to confirm the herpetic infection when suspected and that it is particularly useful when the Papanicolaou smear findings are equivocal.

• The Journal of Internal Korean Medicine
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• v.21 no.2
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• pp.291-297
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• 2000

Objective : In order to find antiviral compounds against Herpes simplex virus type I(HSV-1) and II(HSV-2) from herb medicines, a convenient virus-induced cytopathic effect(CPE) inhibition assay was introduced. Methods : Fourteen purchased herbal medicines, and their toxicity of infected cell and anti-viral activities were evaluated. Among them, the major part of herbal medicines showed cell stability compared with the contrast. Results : Cytotoxic concentration (CC) of the $H_2O$ extracts of Hyongbangpaedoksan against HSV-1 and HSV-2 was 181.12. This is high level cytotoxic concentration compared with the contrast. Therefore, we assumed that the high level cytotoxic concentration of herbal medicine play a major role in improvement of antiviral activity at the first infective cell. But antiviral effect was unable to figure out for selective index(Sl)=CC50/EC50. The other herbal medicines were unable to showed potent anti-HSV activity. Conclusions : The antiviral activation using herbs in this thesis have unlimited objects, to select research object will help to show the direction of antiviral drug development that have less side effect and more excellent efficiency.

• Archives of Pharmacal Research
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• v.20 no.1
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• pp.58-67
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• 1997

In order to find antiviral compounds against Herpes simplex virus type I (HSV-1) and II (HSV2) from natural products, a convenient virus-induced cytopathic effect (CPE) inhibition assay was introduced. More than 300 fractions were prepared by solvent fractionation from sixty collected plants or purchased herbal medicines, and their anti-herpetic activities were evaluated. Among them, several medicinal plants showed potent anti-herpetic activity. Selective indexes (SI) of the EtOAc extract of Caraganae Radix (Caragana sinica) against HSV-1 and HSV-2 were more than 8.06 and 24.79, SI of the MeOH extract of Acer okamotoanum leaves were 3.92 and 3.51, SI of the $CH_{2}Cl_{2}$ extract of Veratri Rhizoma et Radix (Veratrum patulum) were 5.49 and 1.31 and SI of the MeOH extract of aerial part of Osmundae Rhizoma (Osmunda japonica) were more than 3.45 and 1.25, respectively.