Research progress on herpes simplex virus membrane fusion protein interactions / 中国生物制品学杂志

@#Herpes simplex virus(HSV)is a ubiquitous enveloped virus containing double-stranded DNA. HSV-1 infection can cause inflammation of the lips,conjunctivitis and encephalitis,HSV-2 infection can cause genital herpes at many ages,and both viruses can establish lifelong latent infection in the body. Membrane fusion triggered by the interaction of various HSV membrane proteins is an important way for viruses to enter host cells. This review introduced the conserved core fusion mechanism of HSV composed of four viral glycoproteins gD,gH,gL and gB by analyzing the structure of glycoproteins and their interaction modes. Since there is currently no HSV vaccine approved for marketing in the world,it is of great significance to study the mode of action of HSV and host cells for the development of vaccines

Estudio de seroprevalencia de HVS 1-2 en gestantes y recién nacidos de 2017 a 2021

El virus herpes simple (VHS) pertenece a la subfamilia alfa virus, miembro de la familia Herpes viridae. Existen dos tipos de VHS íntimamente relacionados, el VHS tipo 1 (VHS1) y el VHS tipo 2 (VHS2), que causan enfermedades de diversa gravedad. El VHS1 se transmite principalmente por contacto de boca a boca y el VHS2 se transmite por vía sexual; ambos pueden causar herpes genital. La carga de morbimortalidad a nivel mundial derivada de patógenos de transmisión sexual compromete la vida, así como la salud sexual y reproductiva, y la salud del recién nacido. Objetivos: Determinar la seroprevalencia IgG e IgM por VHS1 y VHS2 de los recién nacidos y madres en el periodo de enero 2017 a julio 2021 en un hospital de tercer nivel. Materiales y Métodos: Estudio observacional, retrospectivo de corte transversal de enero 2017 a julio 2021. Se midió anticuerpos IgG e IgM en recién nacidos y gestantes de ultimo trimestre, utilizando el método de ELISA. Resultados: De un total de 4712 serologías IgG e IgM de madres y RN analizados la seroprevalencia de IgG en gestantes fue cercana al 100% con valor similar en los RN (87%), la seroprevalencia de IgM en las madres fue 0,23% y de los RN 0,36% con tendencia ascendente. Conclusión: la seroprevalencia de IgG para VHS es elevada, en cambio la seroprevalencia de IgM en gestantes y recién nacidos en el periodo de estudio es significativamente baja.

The herpes simplex virus (HSV) belongs to the alpha virus subfamily, a member of the family Herpes viridae. There are two closely related types of HSV, HSV type 1 and HSV-2, which cause diseases of varying severity. HSV-1 is transmitted mainly by mouth-to-mouth contact and HSV-2 is transmitted sexually, both of which can cause genital herpes. The global burden of morbidity and mortality from sexually transmitted pathogens compromises life, as well as sexual and reproductive health, and the health of the newborn. Objective: To determine the IgG and IgM seroprevalence for HSV 1 - 2 of newborns and mothers in the period from January 2017 to July 2021 in a third level hospital. Materials and Methods: Observational, retrospective, cross-sectional study of January 2017 to July 2021. IgG and IgM antibodies were measured in newborns and pregnant women in the last trimester, using the ELISA method. Results: Of a total of 4712 IgG and IgM serologies of mothers and newborns analyzed the seroprevalence of IgG in pregnant women was close to 100% with similar value in newborns (87%), IgM seroprevalence in mothers was 0.23% and the RN 0.36% with an upward trend. Conclusion: The IgG seroprevalence for HSV is high, while the IgM seroprevalence in pregnant women and newborns during the study period is significantly low.

Research progress on the mechanisms of the latency and recurrence of herpes simplex virus type Ⅰ in trigeminal ganglion / 国际眼科杂志(Guoji Yanke Zazhi)

Herpes simplex keratitis(HSK), caused by the infection of herpes simplex virus type Ⅰ(HSV-1)in cornea, is a global blinding corneal disease. After the primary infection in ocular surface, HSV-1 is transported into trigeminal ganglion and establishes the life-lasting latency, and it results in recurrent keratopathy. In the process of studying the latent mechanism of HSV, it has been gradually recognized that both the virus itself and the host response regulate the latent process of HSV. In recent years, a large number of research results have been obtained on the molecular mechanisms of invasion, immunity, latency and recurrence of neurotropic viruses, which provide new ideas for the prevention and treatment of HSK. In the present review, the recent progress of HSV latency mechanism in trigeminal ganglion after the primary infection in corneal surface was introduced, and the unsolved basic and clinical problems in HSK were discussed.

The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro / 中西医结合学报

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.

Current Status Of Immunoglobulin M And Immunoglobulin G Seroprevalence Of Torch Infections In Pregnant Women With Bad Obstetric History At A Tertiary Care Hospital

Introduction: TORCH stands for Toxoplasma gondii, Rubella virus, Cytomegalo virus (CMV) and Herpes simplex virus- 2 (HSV-2). These infections are transmitted to the foetus through transplacental route at any time during gestation or sometimes at the time of delivery. The infection may be asymptomatic or mild in mother but associated with inadvertent outcomes for the foetus. One of the causes of BOH is maternal infection. TORCH infection is asymptomatic in pregnant women and on clinical basis it is difficult to diagnose. To study the TORCH infection (IgM and IgG antibodies)Aim: prevalence in pregnant women with Bad Obstetric History. A hospital based cross-sectionalMaterials And Methods: study conducted in Department of Microbiology in collaboration with Department of Obstetrics and Gynecology, SHKM GMC, Nalhar, Nuh, Haryana over a period of one year (February 2020 - January 2021). A total of 90 samples were included in the study including control group. The IgM seroprevalence of TORCH in participants with bad obstetricResults: history was found to be 11.11%. In cases with Bad obstetric history prevalence of IgM Toxoplasma, Rubella, Cytomegalovirus & Herpes Simplex Virus was found as 4.44%, 0%, 2.22% & 4.44% respectively and prevalence of IgG Toxoplasma, Rubella, Cytomegalovirus, & Herpes Simplex Virus was found as 53.33%, 91.11%, 88.89% & 66.67% respectively. This study concluded that a previous history of pregnancy wastage and the serologicalConclusion: screening for TORCH infections during current pregnancy must be considered while managing BOH cases to reduce the adverse fetal outcome

Cervicitis necrótica por co-infección de virus herpes simplex 2 y Mycoplasma genitalium / Necrotic cervicitis for co-infection of herpes simplex virus 2 and Mycoplasma genitalium

Resumen Las cervicitis es una condición frecuente causada principalmente por agentes de transmisión sexual. Su presentación clínica varía desde cuadros asintomáticos hasta procesos inflamatorios extensos, que incluso asemejan un tumor maligno. Presentamos el caso de una adolescente que presentó úlceras genitales, síntomas generales y cérvix necrótico con aspecto tumoral. Los estudios de laboratorio confirmaron una co-infección por virus herpes simplex 2 (HSV-2) y Mycoplasma genitalium. El estudio histológico descartó una neo- plasia. Evolucionó favorablemente al tratamiento antimicrobiano, con recuperación progresiva del aspecto del cérvix. La cervicitis en raras ocasiones se presenta con compromiso necrótico. La co-infección por HSV-2 y M. genitalium, en este caso, pudo ser el determinante del daño cervical y la necrosis. Una evaluación acuciosa y estudio con exámenes diagnósticos de alta sensibilidad y especificidad permitieron hacer un diagnóstico y tratamiento adecuado.

Abstract Cervicitis is a frequent condition caused mainly by sexually trans- mitted agents. The clinical spectrum varies from absence of symptoms to extensive inflammatory processes that may simulate a malignant neoplasm. We present a clinical case of an adolescent with genital ulcers and systemic disease. Speculoscopy revealed a tumoral-looking cervix. Laboratory studies confirm infection with herpes simplex virus 2 (HSV-2) and Mycoplasma genitalium, together with a histological study that ruled out neoplasia. It progresses favorably to antimicrobial treatment, with recovery of the appearance of the cervix. Cervicitis rarely presents with necrotic involvement. Co-infection with HSV-2 and M. genitalium infection may have been the determinant of cervical damage and the necrotic appearance. A thorough evaluation and study with highly sensitive and specific diagnostic tests allowed an adequate diagnosis and treatment.

Qingre Xiaoyanning inhibits emotional stress-induced reactivation of latent herpes simplex virus type 1 in mice / 药学学报

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.

Fulminating herpes simplex hepatitis

ABSTRACT Herpes simplex virus (HSV) is a rare cause of acute hepatitis in patients with chronic immunosuppression, including Crohn's disease. HSV hepatitis has the propensity to cause acute liver failure and death. The presenting signs and symptoms can be nonspecific, thereby causing the diagnosis to go overlooked with inadequate management, leading to a high mortality rate. We report a case of a 31-year-old male on chronic prednisone treatment for Crohn's disease who unexpectedly died. Subsequently, an autopsy showed HSV hepatitis as the cause of death. Thus, although a rare complication, HSV hepatitis should always be kept in mind as a fatal complication in patients with acute hepatitis and chronic immunosuppression.

Construction of recombinant herpes simplex virus 2 expressing enhanced green fluorescent protein using CRISPR/Cas9 / 中华微生物学和免疫学杂志

Objective:To construct a recombinant herpes simplex virus 2 (HSV-2) expressing enhanced green fluorescent protein (EGFP) using clustered, regularly interspaced, short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) technology.Methods:Four strategies for inserting exogenous EGFP gene into HSV-2 genome using CRISPR/Cas9 technology were designed: (1) conventional homology-directed repair: circular two homology arm donor-mediated gene knock-in; (2) linearized single homology arm donor-mediated gene knock-in; (3) homology-independent targeted integration; (4) conventional homology-directed repair-mediated by cell lines stably expressing Cas9 and sgRNA.Results:The recombinant virus HSV-2-EGFP was successfully constructed based on the second, the third and the fourth strategies. The second strategy was the most efficient, followed by the third and the fourth strategies. The purified recombinant virus could stably express green fluorescent protein in seven passages and shared similar growth characteristics in Vero cells to the parental virus.Conclusions:Linearized single homology arm donor could increase the efficiency of gene knock-in, and cell lines stably expressing Cas9 and sgRNA could increase the efficiency of gene knock-in mediated by homology-directed repair.

Protective effects of bicistronic DNA vaccines of herpes simplex virus type 2 glycoprotein D and adjuvant CCL28 on mice / 中华微生物学和免疫学杂志

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.

Protective effects of fusion recombinant DNA vaccine of herpes simplex virus type 2 glycoprotein D and adjuvant CCL19 on mice / 中华微生物学和免疫学杂志

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.

Asociación entre los niveles de linfocitos T CD4 y lesiones bucales de portadores del VIH/sida / Association between CD4 T lymphocyte levels and oral lesions in HIV/AIDS patients

Introducción: Las enfermedades de la cavidad bucal en los pacientes con VIH/sida pueden verse agravadas dependiendo de la respuesta inmunitaria del paciente y los niveles de linfocitos. Objetivo: Relacionar los niveles de linfocitos T CD4 y las principales lesiones bucales en pacientes con el VIH/sida del Hospital Nacional Hipólito Unanue (Lima, Perú), durante el 2018. Métodos: Se realizó un estudio analítico y de corte transversal, entre julio y octubre del 2018, en 65 pacientes hospitalizados, a los cuales se realizó un examen clínico de la cavidad bucal. Se evaluó la presencia de manifestaciones bucales asociadas al VIH/sida; también se clasificó el nivel de linfocitos T CD4 en tres categorías (> 500 cel/mm3, entre 200-500 cel/mm3 y < 200 cel/mm3). Resultados: Un 70,8 por ciento de los pacientes no se encontraba con tratamiento antirretroviral al momento del examen. El nivel promedio de linfocitos T CD4 fue 237,65 cel/mm3, con mayor prevalencia en mujeres. El 56,9 por ciento de los pacientes presentaron lesiones bucales, el sexo masculino fue el más afectado (91 por ciento). La lesión más frecuente fue la candidiasis bucal (44,6 por ciento) y la categoría que presentó mayor frecuencia de lesiones bucales fue la < 200 cel/mm3 (38,5 por ciento; p < 0,05). Conclusiones: El sexo masculino presentó la mayor cantidad de lesiones bucales asociadas a bajos niveles de linfocitos T CD4. La mayor parte de lesiones bucales se presentaron en un nivel de linfocitos T CD4 < 200 cel/mm3. La candidiasis bucal fue la lesión que más se evidenció al momento de realizar el examen clínico(AU)

Introduction: Oral diseases may be aggravated in HIV/AIDS patients depending on their immune response and lymphocyte levels. Objective: Describe the relationship between CD4 T lymphocyte levels and the main oral lesions in HIV/AIDS patients from Hipólito Unanue National Hospital in Lima, Peru, during the year 2018. Methods: An analytical cross-sectional study was conducted of 65 hospitalized patients from July to October 2018. The patients underwent oral clinical examination. Evaluation was performed of the presence of HIV/AIDS-related oral manifestations, and CD4 T lymphocyte levels were classified into three categories: > 500 cell/mm3, 200-500 cell/mm3 and < 200 cell/lmm3. Results: Of the total patients studied, 70.8 percent were not under antiretroviral treatment at the moment of the examination. Average CD4 T lymphocyte level was 237.65 cell/mm3, with higher results among women. 56.9 percent of the patients had oral lesions. Males were more commonly affected (91 percent). The most frequent lesion type was oral candidiasis (44.6 percent), whereas the category presenting the highest frequency of oral lesions was < 200 cell/mm3 (38.5 percent; p < 0.05). Conclusions: Male patients presented the largest number of oral lesions associated to low CD4 T lymphocyte levels. Most of the oral lesions were found at a CD4 T lymphocyte level < 200 cell/mm3. Oral candidiasis was the lesion most commonly found by the clinical examination(AU)

Application of CRISPR/Cas9 technology in the study of herpes simplex virus / 中华微生物学和免疫学杂志

Herpes simplex virus (HSV), the main pathogen of human herpetic diseases, is an attractive viral vector due to a wide range of host cell types and a large capacity of foreign gene. The manipulation on herpes simplex virus genome, up to 152 kb, has been the key process and has undergone the improvement from homologous recombination to bacterial artificial chromosome (BAC) and CRISPR/Cas9. However, homologous recombination is imperfect because the efficiency of recombination is relatively low and the product is too complex to purify. Construction of recombinant HSV based on BAC is time-and labor-consuming. Currently, CRISPR/Cas9 has been applied to genetic engineering of various species by more and more researchers due to its convenience, good repeatability, low cost, and then the manipulation of viral genome is more accurate and efficient. Application of CRISPR/Cas9 in the research of HSV gene function, HSV infection therapy and viral vector were summarized in this review, in order to provide reference for corresponding research.

Qingre Xiaoyanning Capsules alleviate HSV-1 susceptibility induced by emotional stress / 中国中药杂志

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.

Improvement of Transdermal Delivery of Aciclovir Aliphatic Ester Prodrugs by Using Supersaturated System / 中国药房

OBJECTIVE：To prepare supersaturated system of lip ophilic aci clovir（ACV）prodrug，and to increase the cutaneous bioavailability of ACV. METHODS ：Three prodrugs of ACV were synthesized by anhydride acylation ，i.e. aciclovir acetate （ACV-Ace），butyrate（ACV-But）and hexanoate （ACV-Hex）. The structures of ACV and three ACV prodrugs were confirmed by 1H-NMR and HRESI-MS ；the concentrations of ACV and three ACV prodrugs were determined by UPLC-triple quadrupole tandem mass spectrometry ，and saturated solubility of them in different volume fractions of propylene glycol-water solution was calculated. The compound with the greatest potential of form supersaturated system was screened out. The supersaturated system of that compound was prepared by co-solvent method. The effect of hydroxypropyl methylcellulose E 3 （HPMC E 3） on its physical stability was observed by light microscope. Vertical Franz diffusion cells were used to study the effects of degree of supersaturation （DS）and HPMC E 3 on the deposited amount of drug in the excised porcine skin after using the supersaturated system for 1 h. The distribution of ACV in the excised porcine skin was determined by frozen slicing stratified quantitative method after using the supersaturated system and marketed aciclovir cream for 1 h. RESULTS ：Three ACV prodrugs were successfully synthesized. The established quantification methods met the requirements of biological sample analysis. Among all of the three ACV prodrugs ， ACV-Hex showed the lowest saturated solubility in water [ （0.5±0.0）mmol/L] a nd the highest saturated solubility in propylene glycol [（53.4 ± 14.2）mmol/L]，which made it potentially feasible to form supersaturated system with high DS. In 10％propylene glycol-water system ，the addition of HPMC E 3 163.com enabled ACV-Hex supersaturated systems ，with DS no morethan 4，to maintain physical stability within 1 h. The total deposited amount （ACV + ACV-Hex ） in skin after the application of ACV-Hex supersaturated system with DS of 4 for 1 h was higher than that after the application of ACV-Hex supersaturated system with DS less than 4 or without HPMC E 3. In addition ，the concentration of ACV in the basal epidermis （skin thickness was 100-160 mm）by supersaturated system was significantly higher than that of the marketed aciclovir cream （P＜0.05）. CONCLUSIONS：ACV-Hex，the lipophilic prodrug of ACV ，can form stable supersaturated system with DS of 4 in 10％ propylene glycol-water system in the presence of HPMC E 3. High concentration of ACV could be accumulated in the basal epidermis after the skin was exposed to supersaturated system for 1 h，which may be valuable for local treatment skin infection of herpes simplex virus .

Idiopathic ileal volvulus with multiple concomitant infections in a starving man

@#Background: Small bowel volvulus is defined as the torsion of the small intestine, potentially leading to bowel obstruction, gangrene and perforation. It is a rare condition, especially in adults. Case presentation: A 30-year-old man was retrieved from the jungle with severe weight loss and abdominal symptoms. He succumbed to death despite 22 days of intensive medical treatment. An autopsy revealed a ruptured gangrenous ileal volvulus with peritonitis and subdiaphragmatic abscess. Further laboratory analysis detected systemic Candida tropicalis and intestinal gramnegative bacterial sepsis, systemic Zika virus viremia, leptospirosis complicating rhabdomyolysis and disseminated intravascular coagulopathy, Type I Herpes Simplex virus infection of the tongue and upper gastrointestinal tract. The cause of death was the ruptured ileal volvulus, complicated with upper gastrointestinal bleeding due to Herpes simplex virus esophagitis in a malnourished patient with resolving leptospirosis and underlying Zika virus co-infection. Conclusion: Rare clinical scenarios of adult-onset intestinal volvulus with concomitant multiple infections precludes clinical diagnosis and early treatment, leading to devastating consequences of clinical outcome. The positive clinical and postmortem correlation is a good learning lesson in many disciplines of medicine and science.

Taxonomic classification and detection of potential pathogens in healthy voluntary blood donors: Based on metagenomics analysis / 中国输血杂志

【Objective】 To map a comprehensive description of microbiome presented in healthy blood donations in Liangshan Yi Autonomous Prefecture, and detect the potential pathogens and its prevalence. 【Methods】 A total of 1 299 blood samples were randomly selected from healthy blood donors in Liangshan Prefecture. Total nucleic acids were extracted and sequenced by high-throughput sequencing, and the microbiome was determined by metagenomics analysis. Quantitative real-time PCR (qPCR) and ELISA assays were used to detect antibodies against HSV DNA and HSA in each sample. The prevalence of HSV in healthy blood donors was compared in terms of gender, age, occupation, education level, and frequency of donation. 【Results】 3.49GB data were obtained from DNA pool through high-throughput sequencing. After filtering the data of human genome, the DNA sequences annotated as bacteria, parasites / fungi and viruses were 213 057, 10 623 and 15 reads, respectively. A total of 2.79GB data were obtained from cDNA pool, after filtering the data of human genome, the fragments annotated as bacteria, parasites / fungi and viruses were 4 105 600, 18 446 and 0 reads, respectively. The prevalence of IgG and / or IgM antibodies against herpes simplex virus type 1 and 2 were 8.62% (112 / 1 299) and 18.32% (238/1 299), and that of nucleic acid was 0.77 ‰ (1/1 299). 【Conclusion】 The microbiome of healthy blood donors in Liangshan Prefecture and the potential pathogens were identified in this study. Regional specificity of HSV infections emerged in Liangshan Prefecture. Considering the collaboration between HSV-2 and HIV infection, epidemiological investigation of HSV-2 infection should be conducted preferentially among different populations in Liangshan Prefecture and other HIV high prevalence areas in order to benefit the prevention and control of HIV.

Erupción variceliforme de Kaposi y enfermedad de Darier / Kaposi's varicelliform rash and Darier's disease

La erupción variceliforme de Kaposi es una infección cutánea diseminada, causada en la mayor parte de los casos por el virus Herpes simple tipo 1. Se suele presentar en pacientes con alteraciones preexistentes de la barrera cutánea, especialmente en niños con dermatitis atópica. Se comunica el caso de un paciente de 84 años, quien negaba enfermedades cutáneas previas, que consultó por lesiones dolorosas y pruriginosas, en la piel del tórax y el abdomen, de 3 semanas de evolución. Con sospecha de una enfermedad infecciosa viral, bacteriana, ampollar o neutrofílica, se realizó inmunofluorescencia directa para herpes, cultivo y biopsia de piel para estudio histológico. La inmunofluorescencia fue positiva para Herpes simple tipo 1 y el estudio histopatológico mostró cambios compatibles con infección herpética y enfermedad de Darier. La enfermedad de Darier es una genodermatosis infrecuente que se suele manifestar en la adolescencia. Si bien su diagnóstico en la ancianidad es excepcional, este caso ilustra que se debe considerar en todos los pacientes que presenten erupción variceliforme. (AU)

Kaposi's varicelliform rash is a disseminated cutaneous infection, caused by Herpes virus 1. It usually presents in patients with pre-existing skin barrier disorders, especially in children with atopic dermatitis. We report the case of an 84-year-old patient, who reported having no previous skin diseases, who consulted for painful, itchy, 3-week-old skin lesions. As we suspected viral, bacterial, bullous or neutrophilic disease, direct immunofluorescence, culture, and skin biopsy for histological study were performed. Immunofluorescence was positive for Herpes simplex type 1 and the histopathological study showed changes compatible with herpetic infection and Darier's disease. Darier's disease is a rare genodermatosis that usually manifests in adolescence. Although its diagnosis in old age is anecdotal, it should be considered in patients with a varicelliform rash. (AU)

Prevalencia de virus del herpes simple (VHS) en embarazadas de un hospital de referencia de Paraguay, 2019

Resumen Introducción: El Herpes, causada por el virus herpes simple cuyo virus permanece dentro de las terminaciones nerviosas una vez adquiridas, tiene recurrencias que son desencadenadas por estrés, traumatismo, etc. Objetivo: Determinar la prevalencia de Herpes simple virus en embazadas de un Hospital de Referencia de Paraguay durante el 2019 Material y métodos: Estudio observacional, descriptivo de corte trasversal sobre la prevalencia de VHS en embarazadas. Fueron incluidas en el estudio embarazado que acuden al servicio de ginecología y Obstetricia que tengan STORCH (toxoplasmosis, rubéola, citomegalovirus, herpes simple y VIH) entre sus archivos. Los resultados se presentan en tasa de proporciones. Resultados: La prevalencia del HSV en embarazadas fue de del 32,5%(54), n=166, el 37%(20) se encontraban entre 25 a 29 años, el 68,5%(37) provinieron de Zona Urbana, el 48%(26) se encontraban solteras, 59,2%(32) alcanzaron un nivel de estudio secundario. 29,6%(16) llegaron a realizar 3 controles prenatales, el 75,92%(41) se encontraban con edad gestacional < a 20 sem, 42,5%(23) se encontraban en su 2° gestación, el 61,1%(33) no tuvieron parto vaginal anterior, el 88,8%(48) no tuvieron antecedentes de aborto, el 57,4%(31) no tuvieron antecedentes de Cesárea. Conclusión: Se observó que la prevalencia del VHS en embarazadas fue del 32,5%(54) (n=166), se vio más en embarazadas con edades entre 25 y 39 años, en solteras que provenían en mayor porcentaje de zona urbana, con un nivel de estudio alcanzado hasta la secundaria, la mayoría de las embarazadas portadoras del virus se realizaron 3 controles prenatales.

Abstract Introduction: Herpes, caused by the herpes simplex virus whose virus remains within the nerve endings once acquired and has recurrences that are triggered by stress, trauma, etc. Objetive: Determine the prevalence of Herpes simplex virus in pregnant women of a Reference Hospital of Paraguay during 2019 Materials and method: Observational, descriptive cross-sectional study on the prevalence of HSV in pregnant women. They were included in the pregnant study who go to the gynecology and obstetrics department with STORCH (toxoplasmosis, rubella, cytomegalovirus, herpes simplex and HIV) among their files. The results are presented in proportion rate. Results: The prevalence of Herpes simplex virus in pregnant women who attend the Gynecology and Obstetrics service was 32.5% (54), n = 166, 37% (20) were between 25 and 29 years, 68.5% (37) came from the Urban Zone, 48% (26) were single. 59.2% (32) reached a secondary level of study, 29.6% (16) reached 3 prenatal controls, 75.92% (41) were gestational age less than 20 weeks, 42.5% (23) were in their second pregnancy, 61.1% (33) had no vaginal birth before, 27.7% (15) had 1 vaginal, 88.8% (48) had no history of abortion, 11.1% (6) had a history of abortion, 57.4% (31) had no history of Caesarean section. Conclusion: It was observed that the prevalence of the HSV in pregnant women was 32.5% (54) of a total of 166 pregnant women who entered the study, it was seen more in pregnant women between 25 and 39 years old, in single women who came from a greater percentage of urban areas, with a level In the study reached until secondary school, the majority of pregnant women carrying the virus performed 3 prenatal controls.

Diagnosing Herpetic Genital Ulcers in a Resource-Limited Setting- What Works?

Aims: Globally, viral agents, especially herpes simplex virus (HSV), have overtaken the bacterial causes of genital ulcers. Very few laboratories in India, perform culture techniques and polymerase chain reaction (PCR) for diagnosis of genital ulcers. This study aimed to establish the utility of existing tests, which are cheaper and need less technical expertise, when compared to newer tests such as PCR.Study Design: This cross sectional study was carried out to determine the aetiology of genital ulcers, with emphasis on diagnosis of herpetic ulcers, using newer and more accurate methods of diagnosis and evaluating their performance by comparing against viral culture as gold standard test.Place and Duration of the Study: The study was carried out over a period of one year in the Apex Regional Sexually Transmitted Diseases (STD) Centre at Safdarjung Hospital, New Delhi and the Department of Microbiology, AIIMS, New Delhi.Methodology: Fifty three patients with genital ulcers were included in the study. Specimens from ulcers were taken for various tests, including Giemsa stain, ELISA for HSV-1 & 2, PCR and Viral culture for HSV.Results: HSV was identified in 31 of 53 cases (58.5%), including 03 cases of HSV-1, and 28 cases of HSV-2. Sensitivity and specificity of PCR was 90.0% and 84.85%, respectively. Viral culture positivity was 37.7%.Conclusion: Genital herpes is associated with an increased risk of Human Immunodeficiency Virus (HIV) acquisition, and clinical manifestations are diverse; hence a presumptive diagnosis should be confirmed by reliable laboratory tests. Nucleic acid amplification tests (NAAT) are the most sensitive methods for direct detection of HSV. The extensive validation of these tests allows for their application in routine laboratory settings with consistency and greater diagnostic accuracy. When standardised and used, PCR is a highly reproducible, rapid and labour efficient method for HSV detection.