Catarata congênita nas infecções intrauterinas mais comuns (STORCH): revisão de literatura / Congenital cataract in the most common intrauterine infections (STORCH): a review of the literature

RESUMO Objetivo: O objetivo deste estudo foi revisar os aspectos clínicos e patológicos da catarata congênita secundária às infecções por sífilis, toxoplasmose, rubéola, citomegalovírus e herpes simples. Métodos: Trata-se de uma revisão de literatura, na qual foram incluídos artigos de periódicos indexados às bases de dados PubMed®, Cochrane, Lilacs, Embase e SciELO de 2010 a 2023. Resultados: Foram encontrados 45 artigos, e, após seleção, restaram 9 artigos. Além disso, foram adicionados artigos para enriquecer a discussão. A infecção por sífilis está relacionada a alterações corneanas. O citomegalovírus e a toxoplasmose estão relacionados com a coriorretinite e/ou microftalmia. A rubéola é responsável por causar catarata, glaucoma, microftalmia e retinite em sal e pimenta. Conclusão: Foram abordadas as principais etiologias infecciosas e seu quadro clínico na CC. O melhor tratamento para CC é cirúrgico associado a acompanhamento clínico, mas a prevenção é a maneira mais eficaz de combater a CC de etiologia infecciosa. O diagnóstico precoce e o tratamento efetivo previnem alterações e sequelas visuais irreversíveis. Nesse contexto, mostram-se importantes as ações de políticas públicas para o melhor desfecho clínico e melhor qualidade de vida.

ABSTRACT Objective: To review the clinical and pathological aspects of CC secondary to infections by syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes simplex. Methods: This is a literature review. Articles from journals indexed to PubMed, COCHRANE, LILACS, EMBASE and SCIELO from 2010 to 2023 were included. Results: A total of 45 articles were found, which, after selection, remained in 9 articles. Some articles were included to enrich the discussion in this topic. The infection caused by syphilis is related to corneal changes. Cytomegalovirus and Toxoplasmosis due to chorioretinitis and/or microphthalmia. Rubella is responsible for causing cataracts, glaucoma, microphthalmia, and salt and pepper retinitis. Conclusion: The main infectious etiologies and their clinical status in CC were addressed. The best treatment for CC is surgery associated with clinical follow-up, but prevention is the most effective way to combat CC of infectious etiology. Early diagnosis and effective treatment prevent irreversible visual changes and sequelae. In this context, public policy actions are important for the best clinical outcome and better quality of life.

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.

Encefalitis autoinmune posherpética. Caso clínico pediátrico / Autoimmune post-herpes simplex encephalitis. A pediatric clinical case report

La encefalitis por virus herpes simple (VHS) es una causa frecuente de encefalitis grave y potencialmente fatal. La encefalitis autoinmune posherpética (EAPH) afecta a un porcentaje de los pacientes que han presentado encefalitis herpética (EH) y se caracteriza por la aparición de nuevos síntomas neurológico/psiquiátricos, y/o por el empeoramiento de los déficits adquiridos durante la infección viral dentro de un lapso temporal predecible. Se produce por un mecanismo no relacionado con el VHS, sino por fenómenos autoinmunes, y es susceptible de tratamiento con inmunomoduladores. Se presenta el caso de un varón de 5 años de edad con EAPH que requirió tratamiento inmunomodulador, de primera y segunda línea, con buena evolución y remisión de los síntomas.

Herpes simplex virus (HSV) encephalitis is a common cause of severe and potentially fatal encephalitis. Autoimmune post-herpes simplex encephalitis (AIPHSE) affects a percentage of patients who developed herpes simplex encephalitis (HSE) and is characterized by the onset of new neurological/psychiatric symptoms and/or worsening of deficits acquired during the herpes infection within a predictable time frame. It is caused by a mechanism not related to HSV, but by autoimmune conditions, and is susceptible to treatment with immunomodulators. Here we describe the case of a 5-year-old boy with AIPHSE who required first- and second-line immunomodulatory treatment, with an adequate course and remission of symptoms.

Enfermedad de castleman multicéntrica y tuberculosis diseminada en paciente HIV positivo / Multicentric Castleman disease and tuberculosis in HIV positive patient

Resumen Presentamos el caso de un hombre de 40 años, HIV positivo con regular adherencia al tratamiento, que consultó por episodios febriles intermitentes de dos años de evolución, agregando en los últimos dos meses dolor abdominal difuso progresivo y adenomegalias ge neralizadas indoloras. En el laboratorio presentó panci topenia, coagulopatía, hipoalbuminemia y reactantes de fase aguda aumentados. La tomografía computarizada (TC) de tórax, abdomen y pelvis únicamente evidenció hepato-esplenomegalia y adenomegalias generalizadas. Se realizaron múltiples exámenes microbiológicos, in cluyendo cultivos para Mycobacterium sp. de distintas muestras, todos con resultados negativos, a excepción de la RT-PCR para VHH-8. Se tomó biopsia escisional de ganglio iliaco izquierdo con hallazgos compatibles con enfermedad de Castleman. A pesar de reiniciar terapia antirretroviral, la sintomatología progresó, iniciando tratamiento con corticoides y ganciclovir. Luego de una semana, desarrolló falla mulitorgánica y anasarca, que contraindicaron los fármacos iniciados. Se realizó nueva TC de tórax que mostró infiltrados con patrón en árbol en brote en lóbulo superior derecho asociado a derra me pleural bilateral, y a nivel abdominal, progresión de hepato-esplenomegalia y ascitis. Pasó a unidad de cui dados intensivos 48 horas después por falla hepática ful minante. El paciente falleció en pocas horas. Se recibió postmortem el cultivo del aspirado traqueal positivo para Mycobacterium tuberculosis y la punción-biopsia hepática con granulomas no necrotizantes. Nuestro objetivo es remarcar la importancia de pesquisar tuberculosis activa en nuestro país frente a la sospecha de enfermedad de Castleman antes de iniciar tratamiento, y resaltar que la TBC también puede presentarse como complicación infecciosa elevando la morbimortalidad.

Abstract We present the case of a 40-year-old man, HIV posi tive with regular adherence to treatment, who consulted for intermittent febrile episodes during a two-years period, progressive diffuse abdominal pain and painless generalized lymphadenopathy in the last two months. Laboratory analysis showed pancytopenia, altered co agulation tests, hypoalbuminemia, and increased acute phase reactants. Computed tomography (CT) of the chest, abdomen and pelvis revealed hepato-splenomegaly and generalized lymphadenopathy. Multiple microbiological tests were performed, including cultures for Mycobacte rium sp. from different samples, with negative results, except for the RT-PCR for HHV-8. An excisional biopsy of the left iliac lymph node was taken with findings compatible with Castleman's disease. Despite restarting antiretroviral therapy, the symptoms progressed, starting treatment with steroids and ganciclovir. After a week, he developed multiple organ failure and anasarca, which contraindicated the drugs previously started. A new CT of the chest showed infiltrates with a tree-in-bud pattern in the right upper lobe with bilateral pleural effusion, and at the abdominal level, progression of hepatospleno megaly and ascites. He was transferred to the intensive care unit 48 hours later due to fulminant hepatic fail ure. The patient died within a few hours. Postmortem recieved culture results of the tracheal aspirate were positive for tuberculosis (TB) and the histopathology of the liver biopsy showed non-necrotizing granulomas. Our objective is to highlight the importance of screening for active TB, in our country, when Castleman's disease is suspected, before starting treatment, and to stand out that TB can also present as an infectious complication, increasing morbidity and mortality.

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.

Research progress on corneal nerves and substance P in viral keratitis / 国际眼科杂志(Guoji Yanke Zazhi)

Diseases like viral keratitis can harm corneal nerves, which are necessary for maintaining the health and functionality of the cornea. Recent research has shown that corneal nerve pathology affects the infected eye as well as the contralateral one, and that aberrant changes in sympathetic nerves can be seen, with the exception of sensory nerves that correspond to corneal sensation. However, apart from in vivo confocal microscopy and corneal sensation, there have been no additional prognostic indicators that allow clinicians to assess the severity of corneal nerve damage. While multiple functions of corneal nerves are mediated by neuropeptides, substance P, the first topical neuropeptide used in ocular clinical practice, was proved to regulate the process of viral infections, and it is involved in bilateral corneal pathologies through pro-inflammatory and neurotrophic functions in viral keratitis, so it may be used as a diagnostic biomarker or a therapeutic target. Therefore, this review summarized the changes and roles of corneal nerves as well as substance P in viral keratitis, which may serve as a reference for further study into associated mechanisms and clinical applications.

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.

Manifestações clínicas de ceratite ulcerativa periférica com ceratite neurotrófica: desafio terapêutico / Clinical manifestations of peripheral ulcerative keratitis together with neurotrophic keratitis: therapeutic challenge

RESUMO A ceratite ulcerativa periférica é uma infiltração corneana imunomediana associada a doenças autoimunes e inflamatórias sistêmicas. Comumente associada à artrite reumatoide, ela também pode estar associada a outras doenças reumatológicas, inflamatórias e doenças infecciosas. A ceratite ulcerativa periférica é geralmente unilateral e periférica, devido à proximidade com a vasculatura conjuntival. Há tipicamente um defeito epitelial sobrejacente ao infiltrado e afinamento do estromal associado. O objetivo deste relato de caso foi abordar uma das possíveis etiologias de ceratite ulcerativa periférica associada a quadro de ceratite neurotrófica por herpes simplex, apresentar sua apresentação clínica aguda e alertar sobre as implicações do tratamento.

ABSTRACT Peripheral ulcerative keratitis (PUK) is an immune-mediated corneal infiltration associated with autoimmune diseases and systemic inflammation. Commonly associated with rheumatoid arthritis, it may also be associated with other rheumatologic, inflammatory, and infectious diseases. PUK is usually unilateral and peripheral, due to its proximity to the conjunctival vasculature. There is usually an epithelial defect overlying the infiltrate and the associated stromal thinning. The objective of this case report is to address one of the possible etiologies of PUK associated with a picture of neurotrophic keratitis due to Herpes Simplex and its acute clinical presentation, and to warn about possible suggestions for treatment.

Erupción variceliforme de Kaposi en un paciente adulto mayor con desnutrición severa

El eccema herpético o erupción variceliforme de Kaposi, a pesar de ser una infección viral poco frecuente, se considera una urgencia dermatológica, debido a su alto potencial de diseminación, gravedad y mortalidad en adultos. Los pacientes inmunosuprimidos suponen un alto riesgo de colonización cutánea y visceral, además de una mayor probabilidad de presentar otras infecciones causadas por el virus del herpes simple. Se caracteriza por presentar lesiones en piel de tipo vesículas umbilicadas agrupadas o diseminadas que evolucionan a erosiones hemorrágicas perforadas, que se localizan principalmente en cabeza, cuello y tórax; son dolorosas y tardan entre 2-6 semanas en sanar y por lo general se asocian a compromiso sistémico. El diagnóstico es clínico; en caso de duda, se puede utilizar Test de Tzanck, que es una herramienta rápida para confirmar infección por herpes virus; tiene una sensibilidad de 40-80 % y especificidad hasta del 100 %. El manejo consiste en terapia antiviral sistémica; el tratamiento antibiótico está indicado si existe riesgo sobreinfección bacteriana. El tratamiento oportuno de la infección es clave para la evolución hacia la recuperación del paciente.

Eczema herpeticum or Kaposi's varicelliform eruption is a rare viral infection; however, it's considered a dermatologic urgency due to the high potential for dissemination, severity and mortality. Immunosuppressed patients have a high risk of skin and visceral colonization in addition to a higher probability of other infections caused by herpes simplex virus. Kaposi's varicelliform eruption is characterized by vesicopustules, some umbilicated, others eroded and extended in clusters. They may also present hemorrhagic crusts with an erythematous base. The most commonly affected sites are head, neck, and trunk. These lesions are painful, they take from 2 to 6 weeks to heal and are usually associated with systemic signs of infection. Diagnosis is mainly clinical. In case of doubt, the Tzanck allows a rapid diagnostic approach with a sensitivity of 40-80 % and specificity up to 100 % in herpes virus. Antiviral treatment proved to be effective; additional antibiotic treatment is required if there is risk of bacterial infection. The timely treatment of the infection is the key in the evolution towards the recovery of the patient.

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

Genital ulcers caused by sexually transmitted agents,

Abstract Genital ulcers (GUs) represent a diagnostic challenge and can be secondary to neoplastic and inflammatory processes of different causes. Among those of infectious etiology, there are sexually transmitted infections (STIs), a very frequent reason for seeking the health service. The most common agents are herpes simplex virus and Treponema pallidum and, more rarely, Haemophilus ducreyi, Klebsiella granulomatis and Chlamydia trachomatis. A careful dermatological examination offers important diagnostic elements; however, atypical manifestations are very common. Distinctive characteristics of ulcers to look out for include their margin, edge, bottom, and base. Regional lymph node chain alterations should be evaluated regarding their number, size, mobility, consistency, inflammation, and pain on palpation. Diagnostic tests have variable sensitivity and specificity, and molecular tests are currently considered the reference exams. The rapid immunochromatographic tests represented a significant advance, as they can be performed with blood obtained from the digital pulp, offer results in up to 30 minutes, and do not require a laboratory structure. The treatment of persons affected by GU/STIs must be immediate, as it aims to prevent complications, as well as reduce transmission. It is not always considered that people with GUs/STIs have varying degrees of depression, anxiety, and self-reproach, with an impact on relationships. Establishing a bond and trusting the professional is essential for adherence to treatment and preventive measures that must be discussed individually.

Photodynamic Therapy in the Treatment of Herpes Simplex Type 1 Virus Infection / Terapia Fotodinâmica no Tratamento de Infecção pelo Vírus Herpes Simples Tipo 1

Herpes simplex virus type 1 (HSV-1) is primarily responsible for the development of painful mucocutaneous viral lesions in the head and neck region. Antimicrobial photodynamic therapy (aPDT) consists of the use of a photosensitizing chemical substance, which interacts with an appropriate light source under the presence of oxygen, with consequent destruction or microorganisms' inactivation . The aim of this study was to conduct a literature review on the use of aPDT in the treatment of HSV-1, as well as to identify and characterize the main photosensitizing agents used in this technique. This was a narrative literature review, based on the research of scientific articles carried out in the PubMed database, from February to June 2021, using the crossing of the descriptors Decs/Mesh "photodynamic therapy" and "viral infection"; "photodynamic therapy" and "herpes virus". According to the established criteria, a total of 27 articles published in the last 20 years were included. The results demonstrate that despite the scarcity of studies involving aPDT in herpetic lesions, a single application of this therapy and with different protocols improved the clinical appearance and associated symptoms. Thus, antiviral PDT has been shown to be effective in in vitro and in vivo studies, regardless of the dye used. However, more controlled clinical trials need to be carried out in order to establish the real effectiveness of this therapeutic resource in viral infections. (AU)

O vírus herpes simples tipo 1 (HSV-1) é o principal responsável pelo desenvolvimento de lesões virais dolorosas mucocutâneas em região de cabeça e pescoço. A terapia fotodinâmica antimicrobiana (aPDT), por sua vez, consiste no uso de uma substância química fotossensibilizadora, que interage com uma fonte de luz apropriada sob a presença de oxigênio, com consequente destruição ou inativação de microrganismos. O objetivo do presente trabalho foi realizar uma revisão de literatura sobre o uso da aPDT no tratamento de HSV-1, bem como identificar e caracterizar os principais agentes fotossensibilizadores utilizados nessa técnica. Tratou-se de revisão narrativa de literatura, com base na pesquisa de artigos científicos realizada na base de dados PubMed, de fevereiro a junho de 2021, utilizando o cruzamento dos descritores Decs/Mesh "photodinamic therapy" and "viral infection"; "photodynamic therapy" and "herpes virus". De acordo com os critérios estabelecidos, um total de 27 artigos publicados nos últimos 20 anos foram incluídos. Os resultados demonstram que apesar da escassez de estudos que envolvam a aPDT em lesões herpéticas, uma única aplicação desta terapia e com diferentes protocolos promoveu melhora do aspecto clínico e dos sintomas associados. Desta maneira, a PDT antiviral demonstrou ser efetiva em estudos in vitro e in vivo, independente do corante adotado. Entretanto, mais ensaios clínicos controlados precisam ser realizados com o objetivo de se estabelecer a real eficácia deste recurso terapêutico em infecções virais. (AU)

Viraje linfocitario en un caso de encefalitis herpética: La importancia del análisis del líquido cefalorraquídeo. Caso clínico / Lymphocyte shift in a patient with herpetic encephalitis. Report of one case

Central nervous system infections are a medical emergency, due to their high fatality and sequelae. Timely treatment is essential, and should be initially indicated empirically by clinical guidance, without microbiological certainty. Hence the importance of cerebrospinal fluid (CSF) analysis as an etiological and therapeutic guide in the crucial initial hours of management. We report a 57-year-old woman consulting for fever and altered mental status. A brain CAT scan was normal. A lumbar puncture disclosed a CSF with predominance of neutrophils. Suspecting a bacterial meningitis, antimicrobial treatment was started but 48 hours after, the patient did not improve. A new lumbar puncture disclosed a CSF with predominance of lymphocytes. The lymphocyte shift prompted a PCR that was positive for herpes virus. The patient was treated with acyclovir with a good evolution.

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.

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.

Coexisting anti-N-methyl-D-aspartate receptor and anti-glutamic decarboxylase antibody- associated encephalitis after herpes simplex virus encephalitis: a case report / 中华神经科杂志

Herpes simplex virus encephalitis (HSE) is a common form of viral encephalitis, often with a single-phase course. A case of HSE with abnormal mental behavior as the main manifestation, admitted in Peking University Shenzhen Hospital in Octorber 2020, which improved after sufficient antiviral treatment was reported. After 2 months, abnormal mental behavior with memory deterioration recurred. It was considered as anti-N-methyl-D-aspartate receptor antibody combined with anti-glutamic decarboxylase antibody double-positive encephalitis, and improved after rituximab treatment. At present, there is no clinical report of such double antibody positive autoimmune encephalitis secondary to HSE. The purpose of this case report is to raise clinician awareness of post-HSE autoimmune encephalitis.

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.