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OBJECTIVE@#JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.@*METHODS@#HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.@*RESULTS@#HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).@*CONCLUSION@#JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.
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Humans , Caspase 1/metabolism , Inflammasomes/pharmacology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis , Simplexvirus/metabolism , Drugs, Chinese Herbal/pharmacology , Herpes Simplex/drug therapyABSTRACT
In this study, according to TCM theory of "liver qi stagnation forming fire", emotional stress mice model was employed to evaluate the protective effects of Qingre Xiaoyanning on herpes simplex virus type 1 (HSV-1) induced reactivation. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines. BALB/c mice were divided into six groups, including mock group, HSV-1 latency group, HSV-1 reactivation group (HSV-1 latency + stress), low (0.658 g·kg-1·day-1) and high dose (1.316 g·kg-1·day-1) of Qingre Xiaoyanning groups and positive control group (acyclovir, 0.206 g·kg-1·day-1). Except for the normal group and HSV-1 latency group, all mice in other groups received a daily 12-h restraint stress for 4 days. After 7-day treatment of drugs, body weight and recurrent eye infections of mice were recorded. Brain tissues were harvested to monitor HSV-1 antigen distribution by immunohistochemical staining and detect virus titer by plaque assay. In the meantime, the mRNA and protein levels of infected cell polypeptide (ICP27) and glycoprotein B (gB) in the brain tissues were detected by RT-PCR and Western blot, respectively. The level of 4-hydroxynonenal (4-HNE) and expressions of ferroptosis-related proteins were measured by Western blot. The evaluation of malondialdehyde (MDA) content in the brain tissues was conducted by MDA assay commercial kit. The results showed that Qingre Xiaoyanning significantly retarded the decline of body weight of mice induced by HSV-1 reactivation, reduced the activation rate of HSV-1 and recurrent eye infections, declined virus titer of HSV-1, down-regulated gene and protein expressions of ICP27 and gB, and hindered the distribution of HSV-1 antigen in the brain of mice. Meanwhile, Qingre Xiaoyanning also decreased the protein expression of ferroptosis-related proteins, including DMT1, TFR1 and ALOX15 in the brain tissue of HSV-1 reactivated mice. The levels of lipid peroxidation products, 4-HNE and MDA, were also reduced by Qingre Xiaoyanning treatment. All the above results indicate that Qingre Xiaoyanning significantly inhibited HSV-1 reactivation by restraint stress, which might be related to the regulation of ferroptosis. Our findings provide a theoretical basis for the application of "clearing liver-fire" TCM on treatmenting HSV-1 reactivation-related symptoms.
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Objective:To study the protective effects of bicistronic DNA vaccines carrying herpes simplex virus type 2 glycoprotein D (HSV-2 gD) and adjuvant CCL28 sequences that were connected by internal ribosome entry site (IRES) sequence in mouse model.Methods:The recombinant DNA vaccines, pgD-IRES-CCL28 and pCCL28-IRES-gD, encoding HSV-2 gD and adjuvant CCL28 were constructed with IRES sequence. After verified by sequencing, they were intramuscularly injected twice into BALB/c mice. Serum samples and vaginal lavage fluids were collected regularly. Splenocytes, mesenteric lymph node cells and rectal mucosa tissues were separated and collected. The titers of antigen-specific antibodies in immunized mice were analyzed with end-point ELISA. In vitro neutralization assay was used to measure neutralizing antibody titers in serum and vaginal lavage fluid after vaccination and virus challenge. CCL28-responsive immune cells in splenocytes, mesenteric lymph node cells and rectal tissues were detected by chemotaxis experiment and immunohistochemical staining. The protective effects of the bicistronic DNA vaccines were evaluated by fluorescent quantitative PCR, weighing and disease severity assessment. Humoral and cellular immune responses induced by the bicistronic DNA vaccines and their efficacy in immunoprotection were analyzed by comparing with pgD+ pCCL28 group. Results:IgG titers in serum samples and IgA antibody titers in vaginal lavage fluids of mice immunized with pCCL28-IRES-gD were similar to those in pgD+ pCCL28 group. The neutralizing ability of antibodies, the number of rectal mucosal IgA+ plasma cells and CCL28-responsive immune cells in mucosal tissues were increased in pCCL28-IRES-gD group. Serum neutralizing antibodies were not produced immediately in the mice challenged with HSV-2, but no weight loss, disease symptoms or death was observed. However, pgD+ pcDNA3.1 and pgD-IRES-CCL28 were ineffective against HSV-2 infection in mice.Conclusions:The recombinant bicistronic DNA vaccine of pCCL28-IRES-gD could induce stronger mucosal immune response in mice and provide better protective effects.
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Objective:To compare the immune responses to simply mixed and fused recombinant DNA vaccines of herpes simplex virus type 2 glycoprotein D (HSV-2 gD) and molecular adjuvant CCL19 in mice and to evaluate the protective effects.Methods:Gene recombination technology was used to construct recombinant DNA vaccines expressing HSV-2 gD and CCL19 alone or fused together. After verification by sequencing, Western blot and ELISA, BALB/c mice were immunized twice by intramuscular injection. Serum samples and vaginal lavage fluids were collected regularly after immunization. Splenocytes, mesenteric lymph node cells and rectal tissues were collected after immunization. Differences in humoral and cellular immune responses to the two forms of vaccines and their protective effects in mice were analyzed using end-point ELISA, in vitro neutralization assay, immunohistochemical staining, chemotaxis assay, vaginal virus challenge, fluorescence quantitative PCR, weighing and disease severity assessment. Results:The fused recombinant pgD-IZ-CCL19 plasmid could express gD protein and CCL19 protein in vitro, but the level of expressed CCL19 protein by pCCL19-IZ-gD plasmid was less than that by pgD-IZ-CCL19. The mice immunized with pgD-IZ-CCL19 showed higher levels of IgG in sera and IgA in vaginal lavage fluids ( P<0.01) and stronger neutralization ability than the mice vaccinated with pgD+ pCCL19. Compared with other groups, more lymphocytes were recruited in the rectal mucosa, the spleen and mesenteric lymph nodes of mice immunized with pgD-IZ-CCL19. Weight loss or disease symptoms were not observed in the pgD-IZ-CCL19 group after virus challenge. In addition, the positive rate of HSV-2 in vaginal mucosa and the mortality rate in the pgD-IZ-CCL19 group were the lowest. However, pCCL19-IZ-gD turned out ineffective in preventing HSV-2 infection. Conclusions:The fused recombinant DNA vaccine pgD-IZ-CCL19 could induce stronger immune responses in mice and provide better protective effects, which was superior to the simply mixed DNA vaccine.
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In this study, emotional stress-induced herpes simplex virus type 1(HSV-1) susceptibility model was employed to simu-late the pathological state of " depression-induced liver fire", and the protection effect of Qingre Xiaoyanning(QX) in clearing liver fire was investigated. BALB/c mice were randomly divided into a normal group, a HSV-1 group, a restraint stress + HSV-1 group,low-(0. 658 g·kg~(-1)) and high-dose(1. 316 g·kg~(-1)) QX groups, and an acyclovir group. Except for the normal group and the HSV-1 group, the mice in other groups received daily restraint stress for 6 h from day 3 of medication. On day 9 of medication, mice were anesthetized by isoflurane and infected intranasally with HSV-1. Survival rate, weight change, encephalitis symptoms, and eye injury of mice were recorded for 14 d after virus infection. Hematoxylin-eosin(HE) staining and immunohistochemical staining were used to detect pathological changes and HSV-1 antigen distribution. Plaque assay was performed to detect the titer of HSV-1. The protein ex-pression of ICP27 in the mouse brain was detected by Western blot. The experimental results showed that QX could increase the survival rate of HSV-1-infected mice loaded with emotional stress(P<0. 001), reduce the titer of HSV-1 in the mouse brain(P<0. 01), relieve brain inflammation(P<0. 05) and eye injury(P<0. 05), down-regulate the expression of ICP27 related to HSV-1(P<0. 05), and decrease the distribution of HSV-1 antigen in the mouse brain. The results demonstrated that QX significantly reduced the susceptibility to HSV-1 induced by emotional stress, which is expected to provide a theoretical basis for the treatment and preven-tion of HSV-1 infection and promote the clinical development and application of Chinese medicine effective in clearing liver fire.
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Animals , Mice , Capsules , Herpes Simplex , Herpesvirus 1, Human , Mice, Inbred BALB C , Psychological DistressABSTRACT
Background: Herpes simplex virus type 2 (HSV-2) causes genital herpes, a chronic viral infection that is sexually transmitted and often results in genital ulcer disease (GUD) worldwide.Aim: The aim of this study was to determine the prevalence of herpes simplex virus type 2 (HSV-2) IgG and IgM antibodies and the associated risk factors among undergraduate female students of Babcock University.Methods: After ethical approval was obtained, serum samples of 150 consenting female participants (16-35 years) were collected randomly and screened using NADALR HSV-2 IgG/IgM Rapid Antibody Test Cassette (Bulgarian Company for Biotechnology, Sofia, Bulgaria). The demographic and clinical information of the participants were also collected using a structured questionnaire. The results were statistically analyzed using the SPSS version 18.0.Results: The outcome of the study shows that out of the 150 participants screened, 5 (3.3%) were positive for HSV-2 IgG antibody, 4 (2.7%) were positive for HSV-2 IgM; while 2 (1.3%) were positive for both HSV-2 IgG and IgM antibodies. There were no significant differences (P>0.05) in the seropositivity for HSV-2 IgG and IgM antibodies among the study participants on the basis of age distribution. With regards to clinical indication for genital herpes in relation to seropositivity of HSV-2 IgG and IgM antibodies among the study participants, none of the 7 (4.6%) who indicated vaginal itching was seropositive for either HSV-2 IgG or HSV-2 IgM or both. On the other hand, genital lesions were recorded in 0.7% HSV-2 IgG seropositive, 1.3% HSV-2 IgM seropositive and 0.7% HSV-2 both IgG and IgM seropositive. Genital ulcer was recorded among two participants who were either seropositive for HSV-2 IgG (0.7%) or HSV-2 IgM (0.7%). Only one (0.7%) participant indicated inguinal lymphadenopathy, however, the person was HSV-2 IgG/IgM seronegative. Identifiable risk factor significantly (P<0.05) associated with HSV-2 infection include: history of sexually transmitted infections, HIV positive status, and change of sex partners recently.Conclusion: The outcome of this study shows that HSV-2 infection exists among undergraduate female students of Babcock University, Nigeria and therefore appropriate public health measures must be taken to halt the cycle of infection within the University community. Early detection of genital herpes and prompt treatment will help prevent subsequent complications such as genital ulcer disease among young female adults.
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Purpose: The purpose of this study was to investigate the production of IL-27 p28 and EBI3 in the ocular inflammatory sites, and the role of IL-27 signaling in a model of HSV-1 induced herpetic stromal keratitis (HSK). Methods: The BALB/c mice were injected intraperitoneally (24 h before infection) with anti-IL-27 antibody or IgG antibody as control, infected with HSV-1 via corneal scarification, and then injected intraperitoneally with anti-IL-27 antibody or IgG antibody at 1, 3, and 5 days postinfection. Slit lamp and histopathology were used to assess disease outcome. The levels of IL-27 p28 and EBI3 in corneas were determined by western blotting and immunofluorescence. Furthermore, viral titers were determined, and immune cell infiltrates were collected and analyzed by flow cytometry. Results: We found that the levels of IL-27 p28 and EBI3 in corneas were elevated significantly at the peak of HSK, and both of them were expressed simultaneously in the epithelium, stroma, and endothelium of corneas. In the group of anti-IL-27 treatment, the severity of the corneal lesion and CD4+ T cells infiltration were significantly decreased, and the percentage of CD4+ Foxp3+ Tregs was upregulated markedly in the spleen, DLNs and cornea of HSK mice compared to IgG treatment. Conclusion: These results provided evidence that IL-27 as a pathogenic pro-inflammatory cytokine controlled CD4+ Foxp3+ Tregs production in HSK, which ultimately resulted in promoting the progression of HSK and poor prognosis.
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@#Isolated third nerve palsy as the sole manifestation of meningitis is rare. We describe a patient with chronic lymphocytic leukemia who developed third nerve palsy due to HSV2 meningitis. HSV2 PCR was positive in CSF and the patient was partially recovered upon treatment with acyclovir
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Objective To observe and analyze the pathological changes in BALB/c mice infected with herpes simplex virus typeⅡ (HSV-2) through nasal and genital inoculation. Methods Six-week old female BALB/c mice were divided into two groups, experimental and control groups. In the experimental group, the mice were infected with HSV-2 (104 CCID50/20μl per mouse) through nasal and genital tract in-oculation. Accordingly, the mice in the control group were injected with equal volume of PBS. Tissue speci-mens were collected from lung, nervous system and reproductive system for pathological analysis and viral load detection at different time points after infection. Lat gene expression in mouse trigeminal and sacral gan-glia was detected through in situ hybridization. In addition, the proliferation of viruses isolated form trigemi-nal and sacral ganglia of the infected mice was observed in vitro. Results Weight loss and histopathological lesions were observed in the mice of the experimental group 6 d after infection. Major pathological changes in the HSV-2-infected mice through nasal tract inoculation involved the lung and central nervous system( CNS) , including alveolar wall congestion, cerebrovascular cuff response and lymphocyte infiltration. How-ever, the major lesions in the infected mice through genital tract inoculation were found in the reproductive ducts, such as sacral ganglion necrosis, eosinophilia in the vagina and uterus, and ovarian congestion. Re-sults of the viral load detection in tissues and organs of the infected mice were consistent with the pathological changes. The mice infected through nasal tract inoculation had significantly higher viral loads in the nerves and lungs than those by genital tract inoculation, but lower viral loads in the genital tracts and sacral ganglia. Positive expression of lat gene at mRNA level was detected in the trigeminal and sacral ganglia of mice with HSV-2 latency 28 d after infection. In addition, both of the tissue fragments from trigeminal and sacral ganglia had cytopathic effects ( CPEs) on Vero cells. Enhanced expression of lat gene at mRNA level and much severer CPEs were induced by genital tract inoculation than by nasal tract inoculation. Conclu-sions HSV-2 could infect and cause histopathological damages in BALB/c mice through both nasal and genital tracts. In addition, the locations of the pathological lesions were closely related to the mode of infection.
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Objective A lentivirus-mediated colon cancer cell line stably overexpressing human SAMHD1 gene was constructed to observe the effect of this gene on the ability of the cells to resist herpes simplex virus type 1 (HSV-1) infection. Methods p CDH-EF1-MCS-SAMHD1-T2 A-GFP recombinant plasmid was constructed using pCDH-EF1-MCS-T2 A-copGFP lentiviral vector. After confirming successful synthesis with sequencing, the recombinant plasmid and lentivirus packaging plasmids were co-transfected into 293 T cells. The pseudovirus solution was collected and concentrated, then human colon cancer cells were infected with the concentrated solution. The cell line overexpressing SAMHD1 gene was infected with HSV-1 in contrast to the control group, and the virus infection efficiency was assessed by Western blotting and immunofluorescence analyses. Results The pCDH-EF1-MCS-SAMHD1-T2 A-GFP recombinant plasmid was successfully constructed and verified by gene sequencing. Western blotting confirmed the overexpression of the SAMHD1 gene with higher levels of the gene in the transfected cells in contrast to control human colon cancer cell line. Western blotting and immunofluorescence showed that the cell line overexpressing human SAMHD1 gene could effectively inhibit the infection of HSV-1. Conclusion Lentivirus-mediated stable cell line overexpressing human SAMHD1 gene was effective in inhibiting HSV-1 replication and could help us to further investigate the function of SAMHD1.
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@# Objective To understand the awareness of AIDS related knowledge, high risk behaviors, the infection status of HIV, syphilis and HSV-2, and to explore the associated factors with HSV-2 infection among whoremasters in Kaiyuan City, so as to provide scientific evidence for targeted intervention to prevent and control HIV and other STDs. Methods A self-designed questionnaire survey was conducted among whoremasters recruited through outreach activities and snowball sampling. The blood and urine were also collected for corresponding laboratory examination. Results Among the whoremasters, 98.22% had a high awareness of AIDS related knowledge, 9.33% once used drugs, and 14.67% did not use a condom during the latest commercial sex. 62.22% of the whoremasters ever had non-marital sex partners, and of those who had sex with non-marital sex partners in the past year, 59.55% reported using condoms inconsistently. The total infection rate of HIV/syphilis/HSV-2 was 18.22% and the infection rates of HIV, syphilis and HSV-2 were 3.11%, 1.33% and 16.44%, respectively. The older whoremasters were more likely to have a higher HSV-2 infection rate (AOR=1.044,95%CI:1.016-1.073,P=0.002), and those whoremasters not using a condom during the latest commercial sex were more likely to have a higher HSV-2 infection rate (AOR=3.125,95%CI:1.229-7.945,P=0.017). Conclusions Though whoremasters in Kaiyuan City had a high awareness of AIDS related knowledge, they had high-risk behaviors and relatively high HIV and other STDs infection rates. Targeted interventions are needed to improve the risk awareness of STDs infection to promote consistent condom use in both commercial and non-marital sexual behaviors among whoremasters.
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Objective To explore the effect of herpes simplex virus type (HSV-1) infection on expression of β-amyloid (Aβ) in human neuroblastoma cell lines SH-SY5Y. Methods African green monkey kidney cell lines Vero cells were used to amplified HSV-1, and the virus titers were measured. SH-SY5Y cells were infected with HSV-1 3.2×108 plaque forming unit (PFU)/mL at a multiplicity of infection (MOI) of 10 for 12 h or 24 h, and the morphological changes of the cells were observed under microscope. PCR was used to detect the expression of HSV-1 DNA. Double-color immunofluorescence assay was performed to show the expression of Aβ and apolipoprotein E (ApoE). Western blotting was used to detect the expression levels of amyloid precursor protein (APP), melanin metabolic enzyme (MME), ApoE, glycogen synthase kinase-3β (GSK-3β) and phosphorylated glycogen synthase kinase-3β (p-GSK-3β). Results After infection with HSV-1 for 12 h, the SH-SY5Y cells had synapse reduction and neurite retraction and few neurites. And after 24 h of infection, the cells began to aggregate, and were round and shed. Compared with phosphate buffer saline (PBS) control group, the expression of Aβ was significantly increased after infection with HSV-1 for 12 h (P0.01), while the expression of ApoE protein was not significantly changed. After 24 h of infection, the expressions of Aβ and ApoE were significantly increased (P0.05), but the expression of Aβ was significantly lower than that on 12 h of post-infection (P0.01). Western blotting analysis showed that, compared with PBS control group, the expression of APP was significantly decreased on 12 h of post-infection (P0.05), and the expressions of GSK-3β, p-GSK-3β and MME were significantly increased (P0.05). However, the expression of MME was significantly decreased (P0.05) and the expression of ApoE was significantly increased (P0.05) 24 h post-infection. Conclusion HSV-1 infection induces the expression of Aβ in SH-SY5Y cells through promoting APP metabolism and Ser9 phosphorylation of GSK-3β on 12 h of post-infection, and inhibiting the degradation of Aβ on 24 h of post-infection.
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Objective@#To evaluate the anti- herpes simplex virus type 1 (HSV-1) activity of KPC-rg1, a water extract from Cinnamomum cassia, and explore its potential function of broad-spectrum antivirus effect.@*Methods@#In vitro, the changes of morphology of Vero cells were assessed and viral loads were detected after cells were infected with HSV-1 alone and HSV-1 pre-treated with KPC-rg1 respectively. The corneal lesions of mouse and tree shrew corneal infection model were evaluated after they were infected with HSV-1 alone and HSV-1 pre-treated with KPC-rg1 respectively. The antiviral activity of KPC-rg1 against 9 viruses were measured by CPE and GFP reduction assays.@*Results@#The virus replication of HSV-1 infected cells was moderately inhibited by KPC-rg1 in a dose range of 0.0001-1.0 mg/ml, while the cells were completely protected when they were infected with HSV-1 pre-treated with KPC-rg1 (0.001-1.0 mg/ml). The corneal lesions of animals were improved in both mouse and tree shrews models infected with HSV-1 after the treatment of KPC-rg1, while animals were completely protected from infection when HSV-1 pre-treated with KPC-rg1. KPC-rg1 had a potential anti-virus effect on the enveloped viruses such as HSV-1, HCMV, RSV alone and HIV-1.@*Conclusions@#KPC-rg1 is a collosol (Tyndall effect) which would immediately form a stable super-nanoparticle structure of KPC-rg1/virus when encounter virus, and thus the virus coated by KPC-rg1 lost its ability of infection. KPC-rg1 can reduce the suffering by newly or latent virus infection because its encapsulation of virus and inhibition of further infection. Our study added additional proofs of the anti-viral property of the water extract from Cinnamomum cassia, and provided a further basis to develop KPC-rg1 as a drug which could be potentially applied in clinic to treat HSV-1 infection.
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El virus herpes simple tipo 2 (VHS-2), es una infección de transmisión sexual prevalente en el mundo a pesar de los avances diagnósticos y terapéuticos. Según estimaciones en el 2012, se calculaba que existían 417 millones de personas infectadas en todo el mundo. El objetivo de este proyecto fue detectar el VHS-2 en mujeres indígenas del estado Zulia, para ello se seleccionaron 100 mujeres de las etnias wayúu y añú sin discriminar edad y/o paridad. El médico procedió a realizar la toma de muestras con un hisopo de alginato, para el procesamiento de las mismas se utilizó el método de Reacción en Cadena de la Polimerasa (PCR) para detectar el VHS-2, en muestras de origen cérvico-uterino, y el diagnostico citológico se realizó a través de la coloración con hematoxilina- eosina. Se obtuvo un 22% de muestras positivas para VHS-2, los hallazgos obtenidos, demuestran que un porcentaje considerable de las pacientes presentan infección por el VHS- 2, siendo este de suma importancia debido a que el mismo puede contribuir a la progresión de procesos inflamatorios persistentes.
The herpes simplex virus type 2 (HSV-2) is a sexually transmitted infection prevalent in the world; in spite of despite diagnostic and therapeutic advances. According to estimates in 2012, it was calculated that there were 417 million people infected worldwide. The objective of this project was to detect HSV-2 in indigenous women of the Zulia state, for that 100 women of the Wayúu and Añú ethnic groups, were selected without discriminating age and/or parity. The physician proceeded to sample with an alginate swab, for the processing of the same was used the polymerase chain reaction (PCR) method to detect HSV-2 in samples of cervical-uterine origin, and cytological diagnosis was made through staining with hematoxylin-eosin. 22% of HSV-2 positive samples were obtained, the results show that a considerable percentage of patients present HSV-2 infection, which is extremely important because it can contribute to the progression of processes inflammatory agents.
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Background Corneal neovascularization and inflammation occur in herpes simplex keratitis (HSK).Aciclovir (ACV) is an antiviral medication which is primarily used for the treatment of HSV infection.Bevacizumab is an angiogenesis inhibitor which has the ability to slow the growth of corneal neovascularization.However,whether bevacizumab play treating effects on HSK is worth studing.Objective This study attempted to study the effects of bevacizumab on cornea lesion in mouse models of HSK.Methods The solution containing herpes simplex virus type-1 (HSV-1) of Mckrae strain was induced by cultured and infectious Vero cells and prepared by ten-times step dilution with free-serum DMEM,and plaque assay was used to detect the viral titers.HSV-1 of 1 ×l07 plaque-forming unit (PFU) in 0.6 μl was injected into the corneal stroma of 6 to 8-week-old SPF male C57BL/6 mice using a microliter syringe to establish latent HSK mouse models.The models were examined under the slit lamp microscope at day 5,7,11,14 and 17 after modeling as well as day 0,2,4 and 6 after recurrence,and the central cornea touch sensitivity was recorded.The models were divided into ACV-injected group,ACV+bevacizumabinjected group and normal saline-injected group,and 5 μl normal saline with 50 μg ACV,50 μg ACV + 5 μl bevacizumab or 10 μl normal saline was subconjunctivally iujected according to grouping in 4 eyes of each group,respectively.Twelve model eyes were exposed to ultraviolet (UV)-B to induce the recurrent HSK.Corneal wholemounts were prepared at day 9 after modeling for the assessment of corneal neovascularization and nerve fiber distribution by immunofluorescence assay of CD31 and β Ⅲ Tubulin antibodies.The areas of corneal neovascularization and scarring were mcasured with Image J software.The change rate of lesion was calculated and described as a ratio of lesion size at day 8 with day 0 after induction recurrence.Results The modeling success rate was over 80％,and all infected mice showed latent period at day 45 after modeling.Corneal opacification was the most serious at day 7 after modeling and day 2 after recurrence,and the largest corneal neovascular area was seen at day 15 after modeling and at day 2 after recurrence,and the central cornea touch sensitivity was the worst at day 9 after initial infection.The mean corneal lesion area was 3.348 mm2 in the ACV+bevacizumab-injected group,which was smaller than 3.930 mm2 in the ACV-injected group (Z=-2.309,P =0.021).The central corneal sensitivity in the ACV+bevacizumab-injected group was significantly higher than that in the normal saline-injected group (5.50± 0.71 versus 0.50± 1.41,Z =-2.397,P =0.029).The increase rate of corneal lesion area in the ACV +bevacizumabinjected group was evidently lower than that in the normal saline-injected group ([167.10 ± 52.53]％ versus [312.30± 74.18] ％,Z =-1.992,P =0.046).At the 7th day after modeling,the relative expressing levels of thymidine kinase (TK) and infected-cell protein-27 (ICP-27) mRNA in the corneal tissue and trigeminal ganglion were significantly increased at day 7 and reduced at day 45 after modeling,and the factors raised again at day 2 and retreated at day 7 after induction of recurrence.In addition,the expression of LAT mRNA peaked at day 45 after modeling and reduced gradually at day 2 after recurrence until a new increasing peak at day 7 after recurrence (all at P＜0.01).Immunofluorescence showed that compared with the normal saliue-injected group,the corneal new vessels were lessened and corneal never fibers were increased in the ACV-injected group and ACV +bevacizumab-injected group.Conclusions The combination of bevacizumab with ACV can inhibit corneal neovascularization and scarring in HSK mice,and bevacizumab exhibits a synergistic effect with ACV in management of HSK.
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Objective To explore herpes simplex virus type 2 (HSV-2) infection and associated factors among people participating premarital physical examination in 2013-2014 in Minhang District of Shanghai.Methods During 2013 to 2014,people participating premarital physical examination in Minhang District were interviewed with questionnaire regarding HIV/AIDS related Knowledge,sexual behaviors,etc.Blood samples were collected to detect HIV,HSV-2 and syphilis.Results A total of 2 116 participants were investigated,among which 92 were infected with HSV-2,with a prevalence rate of 4.35％.The HSV-2 infection rates were 3.69％ and 5.01％ for male and female,respectively.Multivariate logistic regression analysis showed that for the males,education level of high school and below (OR=2.47,95％CI:1.195-5.108),fiancee infected with HSV-2 (OR=9.29,95％CI:4.279-20.164) were more susceptible to HSV-2.For the females,aged above 25 years (OR=9.29,95％CI:4.279-20.164),census register of other cities in China (OR =2.19,95％CI:1.091-4.378),education level of high school and below (OR =3.37,95％CI:1.721-6.596),never used condoms (OR =3.45,95％CI:1.265-9.392),fiance infected with HSV-2 (OR =8.46,95％CI:3.700-19.351) were more susceptible to HSV-2.Conclusions The prevalence of HSV-2 among premarital population is relatively low in Minhang District.However,low condom use rate leads to an increase in the risk of HSV-2 infection when either partner infected with HSV-2,suggesting increasing condom use between affianced couples.
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Objective To explore herpes simplex virus type 2 (HSV-2) infection and associated factors among people participating premarital physical examination in 2013-2014 in Minhang District of Shanghai.Methods During 2013 to 2014,people participating premarital physical examination in Minhang District were interviewed with questionnaire regarding HIV/AIDS related Knowledge,sexual behaviors,etc.Blood samples were collected to detect HIV,HSV-2 and syphilis.Results A total of 2 116 participants were investigated,among which 92 were infected with HSV-2,with a prevalence rate of 4.35％.The HSV-2 infection rates were 3.69％ and 5.01％ for male and female,respectively.Multivariate logistic regression analysis showed that for the males,education level of high school and below (OR=2.47,95％CI:1.195-5.108),fiancee infected with HSV-2 (OR=9.29,95％CI:4.279-20.164) were more susceptible to HSV-2.For the females,aged above 25 years (OR=9.29,95％CI:4.279-20.164),census register of other cities in China (OR =2.19,95％CI:1.091-4.378),education level of high school and below (OR =3.37,95％CI:1.721-6.596),never used condoms (OR =3.45,95％CI:1.265-9.392),fiance infected with HSV-2 (OR =8.46,95％CI:3.700-19.351) were more susceptible to HSV-2.Conclusions The prevalence of HSV-2 among premarital population is relatively low in Minhang District.However,low condom use rate leads to an increase in the risk of HSV-2 infection when either partner infected with HSV-2,suggesting increasing condom use between affianced couples.
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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 post-treatment 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 IC
ABSTRACT
BACKGROUND: Herpes simplex virus type 2 (HSV-2) is the second most common cause of viral meningitis and the most common cause of recurrent meningitis. Although the incidence of HSV-2 meningitis is high, its clinical characteristics are not well known. The purpose of this study was to review the clinical characteristics and prognosis of HSV-2 meningitis. METHODS: We analyzed patients who were admitted to the Department of Neurology at Severance Hospital with a final diagnosis of HSV-2 meningitis, as confirmed by applying the polymerase chain reaction to the cerebrospinal fluid (CSF) of patients. RESULTS: The study involved 998 patients with aseptic meningitis and 60 patients diagnosed with HSV-2 meningitis. The mean age at meningitis presentation was 32.5 years (range 18-54 years), and 72% of the patients were female. Common clinical symptoms were headache (100%), nausea and/or vomiting (83%), meningismus (57%), and fever (55%). Six patients had a history of genital herpes infection, and 11 had a past history of recurrent meningitis. The CSF study was notable for elevated protein (111.0±53.5 mg/dL, mean±standard deviation) and white cell count (332.0±211.3 cells/µL). The CSF/serum glucose ratio was 0.52±0.90. Various treatments were applied, including conservative care, antiviral agents, empirical antibiotics, and combined treatments. All patients recovered without serious neurologic sequelae. CONCLUSIONS: HSV-2 meningitis is relatively common, as are recurrent episodes. The clinical characteristics of HSV-2 meningitis are similar to those of other types of aseptic meningitis. HSV-2 meningitis is treated using antiviral therapy, and the prognosis is favorable even with conservative treatment.
Subject(s)
Female , Humans , Anti-Bacterial Agents , Antiviral Agents , Cell Count , Cerebrospinal Fluid , Diagnosis , Fever , Glucose , Headache , Herpes Genitalis , Herpes Simplex , Herpesvirus 2, Human , Incidence , Meningism , Meningitis , Meningitis, Aseptic , Meningitis, Viral , Nausea , Neurology , Polymerase Chain Reaction , Prognosis , Retrospective Studies , Simplexvirus , VomitingABSTRACT
La infección esofágica por virus del herpes es una entidad rara que se ha reportado con mayor frecuencia en pacientes inmunocomprometidos. Esta infección afecta principalmente a pacientes con virus de la inmunodeficiencia humana (VIH) y a pacientes que reciben terapia inmunosupresora o quimioterapia. La severidad de los síntomas está relacionada con el grado de afectación esofágica, siendo la odinofagia la presentación clínica más frecuente. Por otro lado, el hallazgo endoscópico más común es la presencia de úlceras múltiples bien circunscritas que se presentan típicamente en el tercio distal del esófago. El tratamiento estándar descrito es el aciclovir oral por 1 a 2 semanas.
Esophageal herpes viral infections are rare condition that have been reported most frequently in immunocompromised patients. This infection primarily affects patients with human immunodeficiency virus (HIV) and patients receiving immunosuppressants or chemotherapy. The severity of symptoms is related to the degree of esophageal involvement. Odynophagia is the most common clinical presentation while the most common endoscopic finding is multiple well-circumscribed ulcers. These typically occur in the distal third of the esophagus. Standard treatment is oral acyclovir for one to two weeks.