Functions of HIV-1 Tat and its association with diseases / 中国生物制品学杂志

@#Acquired immune deficiency syndrome,or AIDS,has been a major infectious disease that troubles the public health in a global scale. Human immunodeficiency virus type 1(HIV-1)is the causative reagent responsible for AIDS development. Even though the highly active anti-retroviral therapy(HAART,or the cocktail therapy)that has been widely applied could effectively suppress the infection and replication of HIV-1,the infected people suffer from other related diseases,such as the HIV-associated neurocognitive disorder(HAND). This paper mainly focused on the function of an important regulatory protein of HIV-1,trans-activator of transcription(Tat),and its correlation with HIV-1 replication and HAND development,so as to clarify the importance of developing anti-AIDS drugs targeting Tat protein

O conhecimento dos profissionais da Atenção Básica em Saúde sobre o Vírus T-linfotrópico Humano / The knowledge of Primary Health Care professionals about the Human T-lymphotropic virus / El conocimiento de los profesionales de la Atención Primaria de Salud sobre el virus linfotrópico T humano

Objetivo: investigar o conhecimento de profissionais de saúde presentes em unidades básicas de saúde (UBS's) sobre o HTLV e as condutas tomadas em caso de infecção. Método:pesquisa quantitativa transversal de abordagem exploratória, sendo realizada por meio de entrevista, com preenchimento de formulário via Google Forms. Realizada em julho de 2023. Resultados:estudo composto por 33 profissionais de saúde, dentre os quais 39% afirmaram desconhecer o HTLV. Essa informação é preocupante, considerando que uma unidade de saúde representa a principal porta de entrada paraos indivíduos em busca de atendimento à saúde. A maioria expressiva, representando 70%, demonstrou conhecimento sobre os meios de prevenção da doença. Porém, a vacinação não foi identificada pela maioria como um método de prevenção, destacando uma percepção menos difundida sobre o papel da vacina nesse contexto. Conclusão:é crucial divulgar pesquisas sobre o tema, criando oportunidades estratégicas para aprimorar tanto a compreensão clínica quanto a empatia no atendimento aos portadores do HTLV, contribuindo assim para a melhoria do diagnóstico, tratamento e qualidade assistencia

Objective:To investigate the knowledge of health professionals present in primary health care units (BHUs) about HTLV and the procedures taken in case of infection. Method:cross-sectional quantitative research with an exploratory approach, carried out through interviews, filling out a form via Google Forms. Carried out in July 2023. Results:study composed of 33 health professionals, of which 39% said they were unaware of HTLV. This information is worrying, considering that a health unit represents the main gateway for individuals seeking health care. The significant majority, representing 70%, demonstrated knowledge about the means of preventing the disease. However, vaccination was not identified by the majority as a prevention method, highlighting a less widespread perception about the role of the vaccine in this context. Conclusion:it is crucial to disseminate research on the topic, creating strategic opportunities to improve both clinical understanding and empathy in the care of HTLV carriers, thus contributing to the improvement of diagnosis, treatment and quality of care.

Objective:To investigate the knowledge of health professionals present in primary health care units (BHUs) about HTLV and the procedures taken in case of infection. Method:cross-sectional quantitative research with an exploratory approach, carried out through interviews, filling out a form via Google Forms. Carried out in July 2023. Results:study composed of 33 health professionals, of which 39% said they were unaware of HTLV. This information is worrying, considering that a health unit represents the main gateway for individuals seeking health care. The significant majority, representing 70%, demonstrated knowledge about the means of preventing the disease. However, vaccination was not identified by the majority as a prevention method, highlighting a less widespread perception about the role of the vaccine in this context. Conclusion:it is crucial to disseminate research on the topic, creating strategic opportunities to improve both clinical understanding and empathy in the care of HTLV carriers, thus contributing to the improvement of diagnosis, treatment and quality of care.

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.

Characteristics of hemagglutinin-neuraminidase gene of human parainfluenza virus type 3 among patients with acute respiratory tract infection in Henan Province / 中华微生物学和免疫学杂志

Objective:To analyze the molecular characteristics of hemagglutinin-neuraminidase (HN) gene of human parainfluenza virus type 3 (HPIV3) among the cases with acute respiratory tract infection (ARI) in Henan Province.Methods:Nasal/throat swab samples collected from patients with severe acute respiratory tract infection (SARI) in Luohe and patients with influenza-like illness (ILI) in Zhengzhou were used in this study. HPIV nucleic acids in the samples were detected using real-time fluorescent PCR. HPIV3-positive samples were subjected to RT-PCR for the amplification of HN genes and the sequences were analyzed with Sanger method. CExpress and MEGA7.0 software were used for sequences editing, evolution tree construction and gene sequence analysis.Results:A total of 374 throat swab samples collected form ARI cases in Luohe and Zhengzhou were tested and 20 (5.3%) of them were positive for HPIV3. Eighteen HPIV3 HN gene sequences were successfully amplified and all belonged to C3 subgroups, including 16 sequences of C3f genotype and two sequences of C3a genotype. The 18 HN gene sequences shared the homology of 97.6%-100.0% in nucleotide and 99.3%-100.0% in amino acid, but the differences between them and the prototype strain Wash/47885/57 were significant. There were 12 amino acid mutations shared by them, including four function-related mutations (H295Y, I391V, D556N and I53T). There were no significant differences in the nucleotide or amino acid sequences as compared with the epidemic strain of China/BCH4210A/2014.Conclusions:The C3f and C3a branches of HPIV3 were the epidemic genotypes in Henan Province in recent years and a local circulating prevalence might be established. Continuous and in-depth monitoring of HPIV3 C3 subtype would be of great significance for the prevention and control of HPIV3-associated diseases.

Virus linfotrópico humano de células T tipo 1 (HTLV-1) en el embarazo / Human lymphotropic virus in T-cell type 1 (HTLV-1) during pregnancy

El HTLV-1 es un retrovirus que afecta principalmente a los linfocitos T-CD4, causando enfermedades como paraparesia espástica o mielopatía, uveítis, dermatitis infecciosas, leucemia/linfoma de las células T del adulto, además de otras enfermedades. Causa una infección crónica de por vida en humanos y su transmisión ocurre a través de la lactancia materna, el contacto sexual y las transfusiones de sangre. En Chile actualmente ocupa el cuarto lugar en notificaciones entre el año 2014-2021, estimándose a nivel mundial más de 20 millones de portadores. El mayor riesgo de transmisión ocurre por lactancia mayor a seis meses y alta carga proviral y altos títulos de anticuerpos en la madre portadora. El objetivo consistió en analizar la situación de la portación del virus HTLV-1 durante el embarazo, determinando su prevalencia, vías de transmisión y complicaciones. Se realizó una revisión bibliográfica sistemática de artículos publicados en bases de datos científicas referidos al virus HTLV-1. Este virus está globalmente diseminado y se presenta en forma endémica en algunas regiones del mundo con prevalencias entre muy elevadas y bajas. En Chile la seroprevalencia en promedio es de 0,124% para HTLV-1. Esta infección no cuenta con tratamiento, solo se tratan los síntomas por lo que mientras esto no cambie, solo es factible reducir la transmisión, incidencia y la morbilidad del HTLV-1 incorporando medidas de control del virus en las intervenciones de control de enfermedades y estrategias de salud pública. La forma más eficiente de transmisión del virus madre-hijo es a través de la leche materna, es necesario implementar la detección prenatal de HTLV-1, en especial en las zonas endémicas, así como también asesorar a las madres HTVL-1 positivas sobre la lactancia materna.

HTLV-1 is a retrovirus that mainly affects CD4-T lymphocytes, causing diseases such as spastic paraparesis or myelopathy, uveitis, infectious dermatitis, adult T-cell leukemia/lymphoma, and other diseases. It causes a lifelong chronic infection in humans and its transmission occurs through breastfeeding, sexual contact and blood transfusions. In Chile, it currently ranks fourth in notifications between the years 2014-2021, with more than 20 million carriers being estimated worldwide. The greatest risk of transmission occurs by breastfeeding for more than six months and high proviral load and high antibody titers in the carrier mother. The objective consisted of analyzing the situation of the carriage of the HTLV-1 virus during pregnancy, determining its prevalence, transmission routes and complications. A systematic bibliographic review of articles published in scientific databases referring to the HTLV-1 virus was carried out. This virus is globally disseminated and occurs endemic in some regions of the world with prevalence between very high and low. In Chile, the average seroprevalence is 0.124% for HTLV-1. There is no treatment for this infection, only the symptoms are treated, so as long as this does not change, it is only feasible to reduce the transmission, incidence, and morbidity of HTLV-1 by incorporating virus control measures into disease control interventions and strategies. of public health. The most efficient form of mother-child transmission of the virus is through breast milk, it is necessary to implement prenatal screening for HTLV-1, especially in endemic areas, as well as counsel HTLV-1 positive mothers on breastfeeding

Expression and function of HLA-G in human T-cell leukemia virus type 1-positive T cells / 中华微生物学和免疫学杂志

Objective:To analyze the expression of human leukocyte antigen G (HLA-G) in human T-cell leukemia virus type 1 (HTLV-1)-positive T cells, and to investigate its role in the occurrence and development of HTLV-1 infection.Methods:The expression of HLA-G in HTLV-1-positive T cell lines (MT2 and MT4) was detected by Western blot and real-time PCR. HLA-G gene in MT2 and MT4 cells was knocked down by siRNA, and the effects of HLA-G on the expression of HTLV-1 Tax and P19 at mRNA and protein levels were detected by Western blot and real-time PCR. Moreover, the changes in cytokine expression in MT2 and MT4 cells were monitored at RNA level after HLA-G gene silencing. The proliferation ability of MT2 and MT4 cells was analyzed by CCK8. Signal transducer and activator of transcription 3 (STAT3) pathway-related proteins were detected by Western blot.Results:Compared with HTLV-1-negative T cells (Jurkat and MOLT4), the expression of HLA-G increased significantly in MT2 and MT4 cells. After knocking down the HLA-G gene with siRNA in MT2 and MT4 cells, the expression of HTLV-1 Tax and P19 at mRNA and protein levels was decreased, and the expression of antiviral cytokines IFN-γ and TNF-α was increased. The proliferation of MT2 and MT4 cells and STAT3 phosphorylation in these cells were decreased.Conclusions:HTLV-1 could induce T cells to overexpress the immune tolerance molecule HLA-G. Silencing HLA-G gene in HTLV-1-positive T cells could promote the production of antiviral cytokines and reduce IL-6 expression and STAT3 phosphorylation, thereby effectively inhibiting the replication of HTLV-1.

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.

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.

Metaanálisis de la validez del inmunodiagnóstico del virus linfotrópico de células T humanas i/ii en bancos de sangre, 2000-2018 / Meta-analysis regarding the validity of the immunodiagnosis of human T-cell lymphotropic virus I/II in blood banks, 2000-2018 / Meta-análise da validade do imunodiagnóstico do vírus linfotrópico de células t humanas I/II em bancos de sangue, 2000-2018

Resumen Objetivo: Evaluar la validez del inmunodiagnóstico del htlv i/ii en bancos de sangre, con base en estudios publicados en la literatura científica. Metodología: Se efectuó un metaanálisis de pruebas diagnósticas siguiendo la guía prisma y las recomendaciones de Cochrane. Se evaluó la calidad metodológica con quadas y se garantizó la reproducibilidad y la exhaustividad. Se realizó también un análisis de efectos aleatorios para la sensibilidad, la especificidad, los cocientes de probabilidad, la razón de momios diagnóstica y la curva característica operativa del receptor (roc) con sus intervalos de confianza (ic) del 95 %. Resultados: Se tamizaron 4604 estudios, de los cuales solo tres cumplieron el protocolo. Se evaluaron 548 infectados con htlv i/ii y 6643 sanos. El inmunodiagnóstico de htlv i/ii presentó una sensibilidad del 99 % (ic95 % = 98,0-99,0), especificidad del 100 % (ic95 % = 99,9-100), cocientes de probabilidad positivo de 315,8 (ic95 % = 128,2-778,5) y negativo de 0,02 (ic95 % = 0,01-0,04), razón de momios diagnóstica de 24373 (ic95 % = 6864-86545) y área bajo la curva roc del 99,9 %. Conclusión: Se dispone de pocos estudios en este campo del inmunodiagnóstico htlv i/ii. El elevado número de sujetos analizados evidenció alta validez del inmunodiagnóstico, lo que resulta determinante para garantizar la inocuidad de las unidades de sangre, la detección de portadores asintomáticos, la disminución de la transmisión y el inicio de tratamiento.

Abstract Objective: To evaluate the validity of the immunodiagnosis of htlv i/ii in blood banks, based on studies published in the scientific literature. Methodology: A meta-analysis of diagnostic tests was carried out following the PRISMA guidelines and Cochrane recommendations. The methodological quality was evaluated with QUADAS, and reproducibility and completeness were guaranteed. A random effects analysis was also performed with respect to sensitivity, specificity, likelihood ratios, diagnostic odds ratio, and receiver operating characteristic curve (ROC) with their 95 % confidence intervals (CI). Results: 4,604 studies were screened, of which only three complied with the protocol. 548 subjects infected with HTLV I/II and 6,643 healthy subjects were evaluated. The immunodiagnosis of HTLV I/II had a sensitivity of 99 % (95 % CI = 98.0-99.0), a specificity of 100 % (95 % CI = 99.9-100), a positive likelihood ratio of 315.8 (95 % CI = 128.2-778.5) and a negative likelihood ratio of 0.02 (95 % CI = 0.01-0.04), a diagnostic odds ratio of 24,373 (95 % CI = 6,864-86,545), and an area under the ROC curve of 99.9 %. Conclusion: Few studies are available in the field of HTLV I/II immunodiagnosis. The high number of subjects analyzed showed high validity of the immunodiagnosis, which is decisive to guarantee the safety of the blood units, the detection of asymptomatic carriers, the decrease in transmission, and the start of treatment.

Resumo Objetivo: Avaliar a validade do imunodiagnóstico do HTLV I/II nos bancos de sangue, baseados nos estudos publicados na literatura científica. Metodologia: Foi realizada uma meta-análise de testes diagnósticos seguindo a guia PRISMA e as recomendações de Cochrane. Foi avaliada a qualidade metodológica com QUADAS e garantiu-se a reprodutibilidade e a integridade. Realizou-se também uma análise de efeitos aleatórios para a sensibilidade, a especificidade, os quocientes de probabilidade, a razão de probabilidade diagnóstica e a Curva Característica de Operação do Receptor (Curva ROC) com seus Intervalos de Confiança (IC) de 95%. Resultados: Foram selecionados 4604 estudos, dos quais somente 3 cumpriram com o protocolo. Foram avaliados 548 infectados com o vírus HTLV I/II e 6.643 saudáveis. O imunodiagnóstico de HTLV I/II apresentou uma sensibilidade de 99% (IC95% = 98,0-99,0), especificidade de 100% (IC95%= 99,9-100), quocientes de probalidade positiva de 315,8 (IC95% = 128,2-778,5) e negativo de 0,02 (IC95% = 0,01-0,04), razão de probabilidade diagnóstica de 24373 (IC95% = 6864-86545) e área sob a curva ROC de 99,9%. Conclusão: São poucos os estudos disponíveis neste campo do imunodiagnóstico HTLV I/II. O elevado número de pessoas analisadas evidenciou alta validade do imunodiagnóstico, o que é decisivo para garantir a inocuidade das unidades de sangue, a detecção de portadores assintomáticos, a diminuição da transmissão e o início do tratamento.

Hiperinfección por Strongyloides stercoralis en un paciente joven con infección por HTLV-1 y colitis ulcerativa / Strongyloides stercolaris hyperinfection in a young patient with HTLV-1 infection and ulcerative colitis

Resumen La estrongiloidiasis es una infección causada por el parásito Strongyloides stercoralis (SS) y se asocia con una alta mortalidad en pacientes inmunosuprimidos debido a una diseminación larvaria y síndrome de hiperinfección. El compromiso de la mucosa gástrica es raro, pero cuando se presenta se caracteriza por sangrado digestivo y emesis persistente. A continuación, se presenta el caso de un paciente de 27 años con síntomas gastrointestinales, antecedente de infección por el virus linfotrópico humano de células T tipo 1 (HTLV-1) y colitis ulcerativa, quien desarrolló síndrome de hiperinfección por SS. Se describe la presentación clínica, diagnóstico, tratamiento y complicaciones derivadas del cuadro infeccioso.

Abstract Strongyloidiasis is an infection caused by the parasite Strongyloides stercolaris (SS) and is associated with high mortality in immunosuppressed patients due to larval spread and hyperinfection syndrome. Gastric mucosal involvement is rare, but when it occurs, it is characterized by digestive bleeding and persistent emesis. The following is the case of a 27-year-old patient with gastrointestinal symptoms, a history of HTLV-1 infection and ulcerative colitis, who developed hyperinfection syndrome with SS. The clinical presentation, diagnosis, treatment and complications arising from the infectious disease are described.

Uso da eletromiografia de superfície na resultância do treinamento muscular inspiratório com carga linear em portadores do vírus linfotrópico humano tipo 1 / Use of surface electromyography in results of inspiratory muscle training with linear load in patients with type 1 human lymphotropic virus

Este estudo visa avaliar por eletromiografia de superfície o comportamento dos músculos inspiratórios no treinamento muscular em voluntários com vírus linfotrópico de célula T humana do tipo 1. Trata-se de um ensaio clínico. Sete voluntários, com idade 58,85 ± 7,2) anos, realizaram treinamento muscular inspiratório domiciliar por 4 semanas, 3 vezes por semana, 30 minutos diários por meio de incentivador de carga linear. Para avaliação utilizou-se os dados de pressão inspiratória máxima e os dados da eletromiografia de superfície nas fases pré (T0), segunda semana (T2) e após a quarta semana (T4) de treinamento. Observou-se aumento progressivo da força muscular inspiratória de T0 a T4 (p = 0,007), assim como, aumento do recrutamento das unidades motoras pela análise da amplitude do sinal eletromiográfico, sendo mais evidente para o músculo esternocleidomastóideo (p = 0,12) em comparação ao músculo diafragma (p = 0,6). Verificou-se que no decurso do treinamento muscular ocorreu melhora significativa da força muscular inspiratória com maior recrutamento das fibras musculares dos músculos analisados na amostra. (AU)

This study aimed to evaluate by surface electromyography the behavior of inspiratory muscles in the muscle training of volunteers with human T-cell lymphotropic virus type 1. This was a clinical trial. Seven volunteers, 58,85 ± 7.21 years old, underwent inspiratory muscle training at home for 4 weeks, 3 times a week, 30 minutes daily by means of a linear load stimulator. The maximum inspiratory pressure data and the surface electromyography data were used for evaluation in the pre (T0), second week (T2) and after the fourth week (T4) training phases. There was a progressive increase in inspiratory muscle strength from T0 to T4 (p = 0.007), as well as an increase in the recruitment of motor units by analyzing the amplitude of the electromyographic signal, being more evident for the sternocleidomastoid muscle (p = 0.12) in comparison to the diaphragm muscle (p = 0.6). During the muscle training inspiratory muscle strength improves with greater recruitment of muscle fibers from the muscles analyzed in the sample. (AU)

A Role of TREX1 in Immune Regulation and Human Diseases / 中国生物化学与分子生物学报

Three prime repair exonuclease 1 (TREX1), also known as DNase IE, is a major 3'-5' restriction exonuclease in most of tissues and cell types of the mammals. The exonuclease activity of TREX1 plays an essential role in maintaining the immune tolerance of the innate immune system, which avoids the excessive activation of the innate immune system and massive production of auto-antibodies induced by the abnormal accumulation of cytosolic DNA. cGAS-STING signaling was identified as an important innate immune response to pathogens and maintained cellular environmental homeostasis. TREX1 prevents occasional leakage of nuclear DNA into the cytosol, which activates cGAS and triggers the downstream type I interferons cascade. Mutations of human TREX1 cause a series of autoimmune diseases, such as Aicardi-Goutieres syndrome (AGS), Familial chilblain lupus (FCL), Systemic lupus erythematosus (SLE) and Leukodystrophy-related retinopathy (RVCL). Besides, TREX1 inhibits the innate immune response to human immunodeficiency virus type 1 (HIV-1) and plays an important role in mediating the viral immune evasion. Moreover, TREX1 acts as an upstream regulator of the DNA sensing pathway, which maintains tumor immune tolerance and prevents cell senescence. Here, we focus on the immune regulation of TREX1 and demonstrate the role of TREX1 in autoimmune diseases, HIV-1 infection, cancer and cell senescence to provide the basic theoretical guidance for human disease therapy.

Molecular analysis of the first dengue fever case in Dapeng New District of Shenzhen City / 上海预防医学

Objective:To analyze the first suspected dengue fever case in Dapeng New District by characterizing the virus and exploring its origin. Methods:Dengue virus nucleic acid in blood sample was identified by real-time fluorescent RT-PCR. The E gene of dengue virus was amplified and sequenced. Homology and phylogenetic tree of this dengue virus were compared with the isolates from other regions. Results:Nucleic acid of dengue virus type 1 was detected in the serum sample from the suspected dengue fever patient. Phylogenetic tree showed that the homology based on nucleotide sequence of E gene of DP-DGR19001 was very similar with the isolates of MG894965/TW/CHN/2016 （99.87%）， LC428079/VNM/2017（99.80%）， MG894867/TW/CHN/2015 （99.60%） and MN512242/GX/CHN/2014 （99.46%）. The deduced amino acid sequence of 5 isolates was 100% identical. The patient had traveled to high-incidence country Cambodia in 14 days before infection. Conclusions:The first suspected dengue fever case in Dapeng New District is caused by dengue virus type 1. The case is an imported dengue fever .

Pre-treatment drug resistance of newly reported HIV-1 infected individuals in Wenzhou / 预防医学

Objective@#To know the pre-treatment drug resistance ( PDR ) status of newly reported human immunodeficiency virus type 1 ( HIV-1 ) infected individuals in Wenzhou, so as to provide guidance for antiretroviral therapy ( ART ). @*Methods@# Totally 232 plasma samples of newly reported HIV-1 infected individuals who had not received ART were collected in Wenzhou in 2019. Virus ( HIV-1 ) RNA was extracted, followed by reverse transcription PCR and nested PCR to amplify the pol region and sequence. Resistance mutations and resistance to non-nucleoside reverse transcriptase inhibitors ( NNRTIs ), nucleoside reverse transcriptase inhibitors ( NRTIs ) and protease inhibitors ( PIs ) was analyzed.@*Results@#The pol region sequences from 199 infected patients were obtained and the incidence of PDR was 8.04% ( 16/199 ). Eight genotypes were detected, including circulating recombinant forms ( CRFs ) CRF07_BC ( 47.24%, 94/199 ) and CRF01_AE ( 29.15%, 58/199 ) which were the dominant types. Two unique recombinant forms ( URFs ) were detected, namely URF( CRF01_AE/BC ) and URF( B/C ) . Thirty-one cases ( 15.58% 31/199 ) had drug-resistant mutations. For NNRTIs, NRTIs and PIs, 20 cases ( 64.52% ) , 2 cases ( 6.45% ) and 9 cases ( 29.03% ) with drug resistance mutations were detected, respectively. The resistance mutations to NNRTIs included K101E, K103N/R, V106I, E138K, V179D/E/T, Y181C, G190A and H221Y. Four cases each had two resistance mutations to NNRTIs. The resistance mutations to NRTIs were V75M and M184V. The resistance mutations to PIs were M46I, L33F and Q58E. For the newly released NNRTI drug Doravirine ( DOR ), two cases were found to have mutations of resistance. @*Conclusions@#The incidence of PDR among newly reported HIV-1 patients in Wenzhou is 8.04%, mainly caused by NNRTIs drug-resistant mutation. Resistance to the new drug DOR has emerged. The surveillance of drug resistance should continue to be strengthened.

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.

Seroprevalence of Herpes Simplex Virus Type 2 and Associated Risk Factors among Undergraduate Female Students of Babcock University Nigeria

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.

Blockade of IL-27 signaling ameliorates herpes stromal keratitis with upregulated CD4+ Foxp3+ regulatory T cells influx in mice

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.

Quality of life, risk behaviors and depression among carriers of hepatitis C virus and human T-cell lymphotropic virus type 1: a comparative study

Abstract Human T-cell lymphotropic virus type 1 (HTLV-1) has low prevalence rates, but is endemic in some regions of the world. It is usually a chronic asymptomatic infection, but it can be associated with serious neurologic and urinary conditions. Hepatitis C virus (HCV) is broadly spread out worldwide. The majority of these infections have a chronic course that may progress to cirrhosis and hepatocellular carcinoma. Objectives: To compare sociodemographic and mental health (risk behaviors, depression, and suicide) aspects, and quality of life among patients with HCV or HTLV-1. Methods: Observational, comparative and cross-sectional study involving outpatients with HCV or HLTV-1 infection. Sociodemographic characteristics, risk behaviors and quality of life were assessed through the questionnaires Mini International Neuropsychiatric Interview - MINI Plus (depression and suicide) and Medical Outcomes Study 36-Item Short-Form Health Survey (quality of life). Univariate and multivariate statistical analyses (hierarchical logistic regression) were conducted. Results: 143 individuals with HCV and 113 individuals with HTLV-1 infection were included. Males were predominant in the HCV group (68.8%) and females in the HTLV-1 group (71.7%). The frequency of risk behaviors (sexual and drug use) was greater in those with HCV (p < 0.05). A past depressive episode was more common in the HTLV-1 group (p = 0.037). Quality of life was significantly worse in the physical functioning, vitality, mental health, and social functioning domains in those with HTLV-1 (p < 0.05). HTLV-1 infection remained independently associated with worse quality of life in multivariate analysis. Conclusions: Risk behaviors are frequent among those infected with HCV. Additionally, despite HTLV-1 being considered an infection with low morbidity, issues related to mental health (depressive episode) and decreased quality of life are relevant.

Origin, tempo, and mode of the spread of DENV-4 Genotype IIB across the state of São Paulo, Brazil during the 2012-2013 outbreak

BACKGROUND Dengue virus type 4 (DENV-4) was first reported in Brazil in 1982 and since then no more cases were detected again in Brazil until 2010, when the virus was reintroduced. Over the following years, the virus spread to several Brazilian states and resulted in about 1,400,000 dengue cases, in 2013. The largest number of cases were documented in the Southeast macro-region. OBJECTIVES To determine the phylogeography of DENV-4 Genotype IIB strains isolated during the epidemics in 2012-2013 in São Paulo, Brazil, we aimed to contextualise the contribution of viruses sampled in different localities across the overall movement of DENV-4 in Brazil. METHODS Based on the envelope gene sequences retrieved from GenBank, we employed a Bayesian phylogeographic approach to assess the spatiotemporal dynamics of DENV-4 Genotype IIB in São Paulo, Brazil. FINDINGS The dispersal dynamics of DENV-4 Genotype IIB in Brazil indicated Rio de Janeiro and Mato Grosso states as the most likely routes toward São Paulo before the 2012-2013 outbreak. Likewise, Guarujá and São José do Rio Preto facilitated viral spread and transmission to other localities in the South and Southeast macro-regions in Brazil. CONCLUSIONS The spread pattern of DENV-4 Genotype IIB strains across the country supports two independent introductions of the virus in São Paulo in a short period of time. Furthermore, São Paulo appears to have played a pivotal role in the dissemination of DENV-4 to other locations in Brazil.