Selective elimination of host cells harboring replication-competent human immunodeficiency virus reservoirs: a promising therapeutic strategy for HIV cure / 中华医学杂志(英文版)

Many seminal advances have been made in human immunodeficiency virus (HIV)/AIDS research over the past four decades. Treatment strategies, such as gene therapy and immunotherapy, are yielding promising results to effectively control HIV infection. Despite this, a cure for HIV/AIDS is not envisioned in the near future. A recently published academic study has raised awareness regarding a promising alternative therapeutic option for HIV/AIDS, referred to as "selective elimination of host cells capable of producing HIV" (SECH). Similar to the "shock and kill strategy," the SECH approach requires the simultaneous administration of drugs targeting key mechanisms in specific cells to efficiently eliminate HIV replication-competent cellular reservoirs. Herein, we comprehensively review the specific mechanisms targeted by the SECH strategy. Briefly, the suggested cocktail of drugs should contain (i) latency reversal agents to promote the latency reversal process in replication-competent reservoir cells, (ii) pro-apoptotic and anti-autophagy drugs to induce death of infected cells through various pathways, and finally (iii) drugs that eliminate new cycles of infection by prevention of HIV attachment to host cells, and by HIV integrase inhibitor drugs. Finally, we discuss three major challenges that are likely to restrict the application of the SECH strategy in HIV/AIDS patients.

The big challenge of SARS-CoV-2 latency: testes as reservoir / El gran desafío de la latencia de SARS-CoV-2: el testículo como reservorio

Abstract In the efforts to explain COVID-19 pathophysiology, studies are being carried out on the correspondence between the expression of SARS-CoV-2 cell receptors and viral sequences. ACE2, CD147 and TMPRSS2 receptors expression could indicate poorly explored potential infection targets. For the genomic analysis of SARS-CoV-2 receptors, using BioGPS information was decided, which is a portal that centralizes genetic annotation resources, in combination with that of The Human Protein Atlas, the largest portal of human transcriptome and proteome data. We also reviewed the most recent articles on the subject. RNA and viral receptor proteins expression was observed in numerous anatomical sites, which partially coincides with the information reported in the literature. High expression in testicular cells markedly stood out, and it would be therefore important ruling out whether this anatomical site is a SARS-CoV-2 reservoir; otherwise, germ cell damage, as it is observed in infections with other RNA viruses, should be determined.

Resumen En el afán por explicar la fisiopatogenia de COVID-19 se están realizando estudios en torno a la correspondencia entre la expresión de receptores celulares de SARS-CoV-2 y las secuencias virales. La expresión de los receptores ACE2, CD147 y TMPRSS2 podría indicar blancos de infección poco explorados. Para el análisis genómico de los receptores de SARS-CoV-2 se optó por utilizar la información del BioGPS, un portal que centraliza los recursos de anotación genética, en combinación con la de The Human Protein Atlas, el portal más grande de datos del transcriptoma y proteoma humanos. También se revisaron los artículos más recientemente respecto al tema. En numerosos sitios anatómicos se observó la expresión de ARN y proteínas de los receptores del virus, que coinciden parcialmente con la información reportada en la literatura. Resaltó la alta expresión en las células de los testículos, por lo que sería importante descartar si este sitio anatómico es un reservorio de SARS-CoV-2; de no ser así, determinar el daño en las células germinales, tal como sucede en infecciones por otros virus ARN.

Pathogenesis of Bovine alphaherpesvirus 2 in calves following different routes of inoculation / Patogênese do alfaherpesvírus bovino 2 em bezerros inoculados por diferentes vias

Bovine alphaherpesvirus 2 (BoHV-2) is the agent of herpetic mammilitis (BHM), a cutaneous and self-limiting disease affecting the udder and teats of cows. The pathogenesis of BoHV-2 is pourly understood, hampering the development of therapeutic drugs, vaccines and other control measures. This study investigated the pathogenesis of BoHV-2 in calves after inoculation through different routes. Three- to four-months seronegative calves were inoculated with BoHV-2 (107TCID50.mL-1) intramuscular (IM, n=4), intravenous (IV, n=4) or transdermal (TD) after mild scarification (n=4) and submitted to virological, clinical and serological monitoring. Calves inoculated by the IV route presented as light increase in body temperature between days 6 to 9 post-inoculation (pi). Virus inoculation by the TD route resulted in mild inflammatory lesions at the sites of inoculation, characterized by hyperemia, small vesicles, mild exudation and scab formation, between days 2 and 8pi. Virus or viral DNA was detected by PCR in the crusts/swabs collected from lesions of 3 out of 4 animals inoculated TD from day 2 to 8pi. Viremia was detected in 3/4 animals of the IM group (from day 4 to 8pi); in 2/4 animals of the IV group (days 6 and 8pi) but not in the TD group. Calves from all inoculated groups seroconverted to BoHV-2 in titers from 4 to 64, as indicated by virus-neutralizing (VN) assays performed in sera collected at day 15pi. Administration of dexamethasone (Dex) to the inoculated calves at day 48pi, did not result in virus reactivation as indicated by lack of virus detection in the blood and/or in inoculation sites and no increase in VN antibody titers. These results demonstrated that BoHV-2 was able to replicate efficiently in calves following different routes of exposure, produced viremia after IM and IV inoculation and was not reactivated by Dex treatment.(AU)

O alfaherpesvírus bovino 2 (BoHV-2) é um agente etiológico da mamilite herpética (BHM), uma doença cutânea e autolimitante do úbere e tetos de vacas. Pouco se sabe sobre a patogênese do BoHV-2, dificultando o desenvolvimento de medicamentos terapêuticos e vacinas. Este estudo investigou a patogênese do BoHV-2 em bezerros após a inoculação por diferentes vias. Bezerros soronegativos de três a quatro meses foram inoculados com BoHV-2 (107TCID50.mL-1) por via intramuscular (IM, n=4), por via intravenosa (IV, n=4) ou transdérmica (TD, n=4) após escarificação leve e submetidos a monitoramento virológico, clínico e sorológico. Os bezerros inoculados pela via IV apresentaram aumento leve da temperatura corporal entre os dias 6 a 9 pós-inoculação (pi). A inoculação do vírus pela via TD resultou em lesões inflamatórias leves nos locais de inoculação, caracterizadas por hiperemia, pequenas vesículas, exsudação leve e formação de crostas, entre os dias 2 e 8pi. O vírus ou DNA viral foi detectado por PCR nas crostas/swabs coletados de lesões de 3 de 4 animais inoculados TD do dia 2 ao 8pi. Viremia foi detectada em 3/4 dos animais do grupo IM (do dia 4 ao 8pi); em 2/4 animais do grupo IV (dias 6 e 8pi), mas não no grupo TD. Bezerros de todos os grupos inoculados soroconverteram o BoHV-2 em títulos de 4 a 64, conforme indicado por ensaios de vírus-neutralização (VN) realizados em soro coletado no dia 15pi. Administração de dexametasona (Dex) nos bezerros inoculados no dia 48pi, não resultou em reativação do vírus, como indicado pela falta de detecção de vírus no sangue e/ou nos locais de inoculação e pela ausência de aumento nos títulos de anticorpos. Estes resultados demonstraram que o BoHV-2 foi capaz de replicar eficientemente em bezerros seguindo diferentes vias de inoculação, produziu viremia após a inoculação IM e IV e não foi reativado pelo tratamento com Dex.(AU)

Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294

ABSTRACT Background: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. Results: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4). Conclusion: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.

Heterogeneity of HIV-1 latent reservoirs / 中华医学杂志(英文版)

Antiretroviral therapy (ART) can effectively inhibit human immunodeficiency virus-1 (HIV-1) replication, but is not curative due to the existence of a stable viral latent reservoir harboring replication-competent proviruses. In order to reduce or eliminate the HIV-1 latent reservoir, characteristics of the latently infected cells need to be intensively studied, and a comprehensive understanding of the heterogenous nature of the latent reservoir will be critical to develop novel therapeutic strategies. Here, we discuss the different cell types and mechanisms contributing to the complexity and heterogeneity of HIV-1 latent reservoirs, and summarize the key challenges to the development of cure strategies for acquired immunodeficiency syndrome (AIDS).

Micetismos: Parte 3: Síndromes tempranos gastrointestinales / Mycetisms Part 3: Early Gastrointestinal Syndromes

En esta Parte 3 de la serie de cuatro artículos sobre micetismos se analizan los síndromes tempranos con síntomas gastrointestinales que se caracterizan por presentar un período de latencia muy corto, de menos de 6 horas después de la ingestión de los macromicetos. Los restantes síndromes tempranos con sintomatología compleja serán tratados en la Parte 4 de la serie. Actualmente se conocen más de 200 especies responsables de síndromes gastrointestinales, pero en este trabajo se abordarán solamente diez ejemplos que involucran los géneros Boletus [Boletus satanas (o Rubroboletus satanas) y Boletus venenatus (o Neoboletus venenata)], Hypholoma, Agaricus (Agaricus xanthodermus), Omphalotus, Lactarius, Russula, Entoloma, Chlorophyllum (Chlorophyllum molybdetes) y Leucoprinus (Leucoprinus birnbaumii). Las toxinas involucradas en estos casos presentan gran variedad estructural, desde proteínas hasta terpenoides, en particular sesquiterpenoides y triterpenoides, vinilglicina, fenol y azocompuestos, pero todas generan la misma sintomatología. Estas sustancias y otros componentes químicos de los hongos suelen ser indigestos, con una susceptibilidad variable entre los consumidores. El tratamiento es de apoyo y es estrictamente para esos casos con cuadros más graves de deshidratación. Normalmente, los casos evolucionan favorablemente después de 12 a 48 horas. Se analizan los síntomas, las toxinas involucradas, los mecanismos de acción, cuando se conocen y las especies causantes de los micetismos.

This part 3 of the series of four articles on mushroom poisoning refers to early-onset gastrointestinal syndromes, which are characterized by a very short latency period of less than 6 hours after mushroom ingestion. The remaining early-onset syndromes with complex symptoms will be treated in Part 4 of the series. Currently, more than 200 species responsible for gastrointestinal syndromes are known, but in this paper only ten examples will be addressed involving the genera Boletus [e.g., Boletus satanas (or Rubroboletus satanas), and Boletus venenatus (or Neoboletus venenata)], Hypholoma, Agaricus (e.g., Agaricus xanthodermus), Omphalotus, Lactarius, Russula, Entoloma, Chlorophyllum (e.g., Chlorophyllum molybdetes), and Leucoprinus (e.g., Leucoprinus birnbaumii). The toxins involved in these cases have a great structural variety, from proteins to terpenoids, in particular sesquiterpenoids and triterpenoids, vinylglycine, phenol, and azocompounds, but all show the same symptoms. These substances and other mushroom chemical constituents are usually indigestible, with varying consumer susceptibility. The treatment is supportive and is strictly for those cases with more severe dehydration. Usually, the cases progress favourably after 12 to 48 hours.The symptoms, toxins involved, mechanisms of action when known, and the species of mushrooms responsible for the mycetisms are analysed.

Nesta parte 3 da série de quatro artigos sobre intoxicação por cogumelos são analisadas as síndromes precoces com sintomas gastrointestinais que se caracterizam por apresentar um período de latência muito curto, de menos de 6 horas, após a ingestão de cogumelos. As síndromes precoces restantes com sintomatologia complexa serão tratadas na Parte 4 da série. Atualmente, são conhecidas mais de 200 espécies responsáveis por síndromes gastrointestinais, mas neste trabalho serão abordados apenas dez exemplos que envolvem os gêneros Boletus [Boletus satanas (ou Rubroboletus satanas) e Boletus venenatus (ou Neoboletus venenata)], Hypholoma, Agaricus (Agaricus xanthodermus), Omphalotus, Lactarius, Russula, Entoloma, Chlorophyllum (Chlorophyllum molybdetes) e Leucoprinus (Leucoprinus birnbaumii). As toxinas envolvidas nestes casos têm uma grande variedade estrutural, desde proteínas até terpenóides, em particular sesquiterpenóides e triterpenóides, vinilglicina, fenol e azo compostos, mas todas apresentam a mesma sintomatologia. Essas substâncias e outros constituintes químicos dos cogumelos costumam ser indigestos, com uma suscetibilidade variável entre aqueles que os consomem. O tratamento é de suporte e é rigorosamente para esses casos com quadros mais graves de desidratação. Normalmente, os casos evoluem favoravelmente após 12 a 48 horas. São analisados os sintomas, as toxinas envolvidas, os mecanismos de ação, quando conhecidos, e as espécies de cogumelos responsáveis pelas intoxicações.

Mechanisms of herpes simplex virus latency and reactivation / 浙江大学学报·医学版

Herpes simplex virus (HSV), including HSV-1 and HSV-2, is an important pathogen that can cause many diseases. Usually these diseases are recurrent and incurable. After lytic infection on the surface of peripheral mucosa, HSV can enter sensory neurons and establish latent infection during which viral replication ceases. Moreover, latent virus can re-enter the replication cycle by reactivation and return to peripheral tissues to start recurrent infection. This ability to escape host immune surveillance during latent infection and to spread during reactivation is a viral survival strategy and the fundamental reason why no drug can completely eradicate the virus at present. Although there are many studies on latency and reactivation of HSV, and much progress has been made, many specific mechanisms of the process remain obscure or even controversial due to the complexity of this process and the limitations of research models. This paper reviews the major results of research on HSV latency and reactivation, and discusses future research directions in this field.

Detection of equine herpesvirus 1 and 4 and its association with latency-associated transcripts in naturally infected horses in Colombia / Detección de los herpesvirus equinos 1 y 4 y su relación con transcriptos asociados a la latencia en caballos infectados naturalmente en Colombia

ABSTRACT Objective. Determine the presence of antibodies and viral genomes of EHV-1 and EHV-4, as well as to detect the presence of latency associated transcripts (LATs) in a selected population of Colombian horses. Materials and methods. Serum samples, submandibular lymph nodes and trigeminal ganglion were obtained from 50 horses and analyzed. Sera were evaluated for the presence of antibodies against EHV-1 and EHV-4 while tissues were initially evaluated for the presence of viral genome by nPCR. Finally, samples were used for the detection of LATs through RT-PCR. Results. In general, 6/50 samples showed antibodies to EHV-1 and 44/50 were positive for EHV-4. As for viral genome detection, 10/50 samples were positive for EHV-1 and 30/50 were positive for EHV-4; in addition, 22/35 horses positive for EHV DNA were positive for LATs. The use of these tests led to eight possible combinations of results. Conclusions. The evidence used shows that horses can have simple viral infection, co-infections with both viruses, latency due to the presence of LATs and the simultaneous presence of LATs and viral genome replication at a given time. It contributes to the understanding of the behavior of the disease in Colombia and calls attention to the importance of implementing complementary diagnoses to the serology for the control of these viruses.

RESUMEN Objetivo. Determinar presencia de anticuerpos y genoma viral de EHV-1 y EHV-4, como también detectar la presencia de transcriptos asociados a latencia (LATs) en una población seleccionada de caballos colombianos. Materiales y métodos. Muestras de suero, nódulos linfáticos submandibulares y ganglio trigémino se obtuvieron de 50 caballos y fueron analizadas. Los sueros se evaluaron para la presencia de anticuerpos contra EHV-1 y EHV-4 mientras que los tejidos se evaluaron inicialmente para la presencia de genoma viral por nPCR. Finalmente, las muestras se emplearon para la detección de LATs a través de RT-PCR. Resultados. En general, 6/50 muestras mostraron anticuerpos para EHV-1 y 44/50 fueron positivos para EHV-4. En cuanto a la detección del genoma viral, 10/50 muestras fueron positivas para EHV-1 y 30/50 fueron positivas para EHV-4; además, 22/35 caballos positivos para DNA de EHV fueron positivos para LATs. El empleo de estas pruebas llevó a ocho posibles combinaciones de resultados. Conclusiones. Se confirma la presencia de estos virus en la población equina colombiana. Las pruebas empleadas demuestran que los caballos pueden tener infección viral simple, co-infecciones con ambos virus, estado de latencia debido a la presencia de los LATs y presencia simultánea de LATs y de replicación de genoma viral en un momento dado. Se aporta al entendimiento del comportamiento de la enfermedad en Colombia y se llama la atención sobre la importancia de implementar diagnósticos complementarios a la serología para el control de estos virus.

Revisión sistemática: estrategias virales para la inducción de cáncer "virus de Epstein-Barr: latencia y mecanismos asociados a la oncogénesis viral" / Viral strategies for cancer induction "Epstein-Barr virus: latency and mechanisms associated with viral oncogenesis"

Resumen La infección crónica con virus oncogénicos es responsable de aproximadamente el 20% de todos los cánceres reportados en humanos, este proceso de oncogénesis viral presenta una naturaleza compleja, multietapa y multifactorial. Un ejemplo de ello es el Virus de Epstein- Barr (EBV), un herpesvirus que infecta de manera latente a más del 90% de la población. Aunque la infección a menudo cursa de manera asintomática, el EBV es capaz de modificar su expresión genómica estableciendo diferentes fases de latencia, alterando así el metabolismo de sus células blanco, como son los linfocitos B y las células epiteliales, proceso que resulta determinante en la aparición y desarrollo de diferentes patologías que van desde la mononucleosis infecciosa hasta procesos oncológicos como el linfoma de Burkitt, el cáncer gástrico o el cáncer nasofaríngeo.

Abstract Chronic infection with oncogenic viruses is responsible for approximately 20% of all cancers worldwide in humans, this viral transformation represents a complex, multistage and multifactorial process. An example is the Epstein-Barr virus (EBV), a herpesvirus that latently infects over 90% of the population. Although the infection often courses asymptomatically, EBV is able to modify its genomic expression by establishing different latency phases, thus altering the B lymphocytes and epithelial cells metabolism, a determinant process in the appearance and development of different pathologies ranging from infectious mononucleosis to oncological processes such as Burkitt's lymphoma, gastric cancer and nasopharyngeal cancer.

Recognition criteria for occupational cancers in relation to hepatitis B virus and hepatitis C virus in Korea

The goal of this study was to review the scientific basis for the recognition of occupational cancer, in relation to hepatitis viral infections in Korea. Most Hepatitis B virus (HBV) infections in Korea occur as vertical infections, but these are decreasing rapidly due to vaccination. Hepatitis C virus (HCV) is known to be transmitted through parenteral routes, but the transmission route is often unclear. Most occupational infections of hepatitis virus involve accidental injuries of medical institution workers while using virus-contaminated medical devices. Many cohort studies and case-control studies have consistently reported that HBV and HCV infection increases the risk of hepatocellular carcinoma (HCC) and the strength of this association is high. Non-Hodgkin's lymphoma appears to be associated with HCV. Cholangiocarcinoma, pancreatic cancer, leukemia, and thyroid cancer are considered to be less related or unrelated to epidemiological causation. There are no uniform international specific criteria for occupational cancer caused through occupational exposure to a hepatitis virus. In establishing appropriate standards applicable to Korea, there should be sufficient consideration of latency, virus exposure levels and frequency, and other cancers, apart from HCC. In conclusion, we recommend keeping the current specific criteria. However, if a worker is injured at work when using a sharp medical device, and HBV and HCV viral infections are confirmed through serologic tests; if the worker is diagnosed as having a chronic HBV or HCV infection, a subsequent HCC (or Non-Hodgkin's lymphoma following chronic HCV infection) can then be considered highly related to the worker's occupation.

Description of an in vivo oral mucosa HSV-1 infection model in mice

In this work, we established an in vivo murine model of herpes simplex virus type 1 (HSV1) infection involving inoculation by scarification of the oral mucosain order to study its dissemination towards the trigeminal ganglion (TG). Both viral DNA and infectious virions were detected on the third day postinfection (p.i.). Viral proteins revealed by immunohistochemistry were mainly found at seven days p.i., when the latencyassociated transcript (LAT) was also detected. This model simulated the dissemination process of HSV1, which could be used to study herpes pathogenesis starting in the oral mucosa (AU)

Con el propósito de estudiar la dispersión de del Herpes Simplex Virus tipo 1 (HSV1) desde la mucosa oral hasta los ganglios trigeminales, en el presente trabajo se estableció un modelo de infección en ratones, haciendo inoculación por escarificación en la mucosa oral. Tanto ADN viral como viriones infecciosos se detectaron en los ganglios trigeminales al dia 3 postinfección (p.i.). Las proteínas virales se detectaron principalmente al día 7 p.i. cuando los transcritos asociados a latencia también fueron encontrados. El modelo de infección simula adecuadamente el proceso de dispersión del HSV1 y puede ser usado para el estudio de la patogénesis por herpes después de la infección primaria en la mucosa oral (AU)

Identification of Epstein-Barr Virus in the Human Placenta and Its Pathologic Characteristics

Epstein-Barr virus (EBV), a common pathogen in humans, is suspected as the cause of multiple pregnancy-related pathologies including depression, preeclampsia, and stillbirth. Moreover, transmission of EBV through the placenta has been reported. However, the focus of EBV infection within the placenta has remained unknown to date. In this study, we proved the expression of latent EBV genes in the endometrial glandular epithelial cells of the placenta and investigated the cytological characteristics of these cells. Sixty-eight placentas were obtained from pregnant women. Tissue microarray was constructed. EBV latent genes including EBV-encoding RNA-1 (EBER1), Epstein-Barr virus nuclear antigen 1 (EBNA1), late membrane antigen (LMP1), and RPMS1 were detected with silver in situ hybridization and/or mRNA in situ hybridization. Nuclear features of EBV-positive cells in EBV-infected placenta were compared with those of EBV-negative cells via image analysis. Sixteen placentas (23.5%) showed positive expression of all 4 EBV latent genes; only the glandular epithelial cells of the decidua showed EBV gene expression. EBV infection status was not significantly correlated with maternal, fetal, or placental factors. The nuclei of EBV-positive cells were significantly larger, longer, and round-shaped than those of EBV-negative cells regardless of EBV-infection status of the placenta. For the first time, evidence of EBV gene expression has been shown in placental tissues. Furthermore, we have characterized its cytological features, allowing screening of EBV infection through microscopic examination.

Research Progress in Mechanisms Associated with Latent Infection in Humans by the Cytomegalovirus / 病毒学报

The human cytomegalovirus (HCMV) is a widespread herpesvirus. Virus reactivation from latency can lead to stillbirth, miscarriage, fetal anomalies, and intrauterine growth retardation. During latent infection with the HCMV, the virus can be cleared by the immune response or apoptosis of host cells. However, the HCMV has developed several strategies to manipulate expression of its genes and the microenvironment of host cells. Recent studies have shown that latent infection with the HCMV is associated with viral: regulation of early expression of genes; evasion of cell death; evasion of the immune response; regulatin of non-coding RNAs. This review summarizes recent research progress on the mechanisms underpinning latent infection with the HCMV.

Percepción parental de la salud psicofísica, estado nutricional y salud bucal, en relación con características sociodemográficas en niños de Bariloche, Argentina: estudio epidemiológico / Parental perception of psychophysical health, nutritional status and oral health in relation to sociodemographic characteristics in children in Bariloche, Argentina: an epidemiological study

Introducción. Existen evidencias de la asociación de determinantes sociales con la salud infantil. Objetivo. Identificar características sociodemográficas asociadas a desigualdades en la salud infantil y evaluar el efecto acumulado sobre la salud de factores de riesgo basados en estas características. Población y métodos. Evaluamos niños de 4-13 años, de Bariloche, entre junio de 2008 y mayo de 2009. Características sociodemográficas consideradas: nivel socioeconómico, educación materna, embarazo adolescente, cobertura médica, inseguridad y hábitos familiares. Valoramos la percepción parental de la salud física y socioemocional, el estado nutricional y la salud bucal en relación con dichas características y con la acumulación de factores de riesgo. Utilizamos encuesta, antropometría y examen bucal. Resultados. Participaron 180 escolares. El nivel educativo materno se asoció con la salud física, socioemocional y bucal del niño. El porcentaje de niños con piezas faltantes o caries fue 77% entre aquellos cuyas madres, como máximo, habían completado el primario, comparado con 13% entre aquellos cuyas madres habían completado estudios terciarios/universitarios. La posibilidad de percepción de salud física y socioemocional no óptima aumentó con cada factor de riesgo 1,8 y 1,4 veces, respectivamente, y la posibilidad de caries o piezas faltantes se duplicó con cada factor de riesgo adicional. El 27,3% de los escolares presentó sobrepeso y el 8,7%, obesidad, y no se encontró asociación con características sociodemográficas. Conclusiones. El bajo nivel socioeconómico familiar y educativo materno se asoció con una mayor prevalencia de resultados de salud desfavorables. Múltiples factores de riesgo tienen un efecto acumulado sobre la percepción parental de la salud física y socioemocional y la salud bucal.

Introduction. There is evidence of an association between social determinants and child health. Objective. To identify sociodemographic characteristics related to child health inequalities and to analize the cumulative effect on health of risk factors based on these characteristics. Population and Methods. We evaluated 4-13 year-old children in Bariloche between June 2008 and May 2009. The following sociodemographic characteristics were taken into account: socioeconomic level, maternal education, adolescent pregnancy, medical coverage, unsafeness, and family habits. We assessed parental perception of physical, and social and emotional health, nutritional status and oral health in relation to these characteristics and the accumulation of risk factors. We used survey, anthropometry and oral examination. Results. One hundred and eighty students participated. The level of maternal education was associated with the child's physical, social and emotional, and oral health. The percentage of children with missing teeth or cavities reached 77% among those whose mothers had, at most, completed primary school, compared to 13% among those whose mothers had completed tertiary school or university. The possibility of perceiving a non-optimal physical, and social and emotional health increased 1.8 and 1.4 times with each risk factor, respectively, and the possibility of having missing teeth or cavities was twice as much with each additional risk factor. Overweight and obesity was observed in 27.3% and 8.7% of students, respectively, and no relationship was found with sociodemographic characteristics. Conclusions. A low family socioeconomic level and a low maternal education level were associated with a higher prevalence of unfavorable health outcomes. Multiple risk factors have an cumulative effect on parental perception of physical, social and emotional, and oral health.

Validation of the Comfort scale for relatives of people in critical states of health / Validação da escala de conforto para familiares de pessoas em estado crítico de saúde / Validación de la escala de confort para familiares de personas en estado crítico de salud

AbstractObjective: this methodological study aims to present the construct validity of the Comfort scale for family members of people in a critical state of health (ECONF).Method:this is a methodological study. The sample was made up of 274 family members of adults receiving inpatient treatment in six Intensive Care Units (ICU) in the State of Bahía responded to 62 items distributed in 7 dimensions. The validation procedures adopted were based on the techniques of the Classical Test Theory.Results: the analysis of dimensionality was undertaken through principal components analysis, a scale being obtained with 55 items distributed in four factors: Safety, Support, Family member-relative interaction and Integration with oneself and the everyday. The analysis of the items' , discriminative power, undertaken by the item-total correlation-coefficient showed a good relationship of the items with their respective factors. From the ECONF's reliability test, from the analysis of internal consistency, a raised Alpha Cronbach coefficient was obtained for the 4 factors and the general measurement.Conclusion:the comfort scale presented satisfactory psychometric parameters, thus constituting the first valid instrument for evaluating the comfort of family members of people in a critical state of health. The advance made by the study lies in its theoretical framework on comfort, and provides the health team with a scale based on empirical evidence.

ResumoObjetivo:validar a Escala de Conforto para Familiares de pessoas em estado crítico de saúde.Método:trata-se de estudo metodológico. A amostra foi constituída por 274 familiares de pessoas adultas internadas em seis unidades de terapia intensiva que responderam a 62 itens, distribuídos em 7 dimensões. Os procedimentos de validação adotados foram embasados nas técnicas da Teoria Clássica dos Testes.Resultados:a análise da dimensionalidade foi realizada por meio da análise por componentes principais, obtendo-se uma escala com 55 itens distribuídos em 4 fatores: segurança, suporte, interação familiar/ente e integração consigo e com o cotidiano. A análise do poder discriminativo dos itens, realizada pelo coeficiente de correlação item-total, mostrou boa relação dos itens com seus respectivos fatores. O exame da fidedignidade da escala, por meio da análise da consistência interna, apresentou coeficiente alfa de Cronbach elevado para os 4 fatores e a medida geral.Conclusão:a Escala de Conforto apresentou parâmetros psicométricos satisfatórios, constituindo-se no primeiro instrumento válido para a avaliação do conforto de familiares de pessoas em estado crítico de saúde. A pesquisa avançou na construção de um referencial teórico sobre o conforto, e disponibilizou à equipe de saúde uma medida pautada em evidências empíricas.

ResumenObjetivo:validar la Escala de Confort para Familiares de personas en estado crítico de salud.Método:se trata de un estudio metodológico. La muestra estuvo constituida por 274 familiares de personas adultas, internadas en seis unidades de terapia intensiva, que respondieron a 62 ítems, distribuidos en 7 dimensiones. Los procedimientos de validación adoptados fueron basados en las técnicas de la Teoría Clásica de las Pruebas.Resultados:el análisis de la dimensionalidad fue realizada por medio del análisis por componentes principales, obteniéndose una escala con 55 ítems distribuidos en 4 factores: seguridad, soporte, interacción familiar/ente e integración consigo y con lo cotidiano. El análisis del poder discriminatorio de los ítems, realizado por el coeficiente de correlación ítem-total, mostró buena relación de los ítems con sus respectivos factores. El examen de confiabilidad de la escala, realizado por medio del análisis de consistencia interna, presentó un coeficiente Alfa de Cronbach elevado para los 4 factores y la medida general.Conclusión:la Escala de Confort presentó parámetros psicométricos satisfactorios, constituyéndose en el primer instrumento válido para la evaluación del confort de familiares de personas en estado crítico de salud. La investigación avanzó en la construcción de un referencial teórico sobre el confort, y suministró al equipo de salud una medida guiada en evidencias empíricas.

Evasión de la respuesta inmune por virus herpes simplex / Immune evasion by herpes simplex viruses

Herpes simplex viruses and humans have co-existed for tens of thousands of years. This long relationship has translated into the evolution and selection of viral determinants to evade the host immune response and reciprocally the evolution and selection of host immune components for limiting virus infection and damage. Currently there are no vaccines available to avoid infection with these viruses or therapies to cure them. Herpes simplex viruses are neurotropic and reside latently in neurons at the trigeminal and dorsal root ganglia, occasionally reactivating. Most viral recurrences are subclinical and thus, unnoticed. Here, we discuss the initial steps of infection by herpes simplex viruses and the molecular mechanisms they have developed to evade innate and adaptive immunity. A better understanding of the molecular mechanisms evolved by these viruses to evade host immunity should help us envision novel vaccine strategies and therapies that limit infection and dissemination.

Los virus herpes simplex y humanos co-existen desde decenas de miles de años. Esta prolongada relación se ha traducido en la evolución y selección de determinantes virales para evadir la respuesta inmune y recíprocamente la evolución y selección de componentes inmunes del hospedero para limitar la infección viral y el daño que producen. Actualmente no existen vacunas para evitar la infección de estos virus o terapias que la curen. Los virus herpes simplex son neurotrópicos y permanecen latentes en neuronas de ganglios trigémino y dorsales, reactivándose esporádicamente. La mayoría de las recurrencias por virus herpes simplex son sub-clínicas y por tanto pasan inadvertidas. Aquí discutimos los pasos iniciales de la infección porvirus herpes simplex y los mecanismos moleculares que estos virus han desarrollado para evadir la respuesta inmune innata y adaptativa. Una mejor comprensión de los mecanismos moleculares evolucionados por estos virus para evadir la respuesta inmune del hospedero deberían ayudarnos visualizar nuevas estrategias para desarrollar vacunas y terapias que limiten su infección y diseminación.

Epstein-Barr virus latent genes

Latent Epstein-Barr virus (EBV) infection has a substantial role in causing many human disorders. The persistence of these viral genomes in all malignant cells, yet with the expression of limited latent genes, is consistent with the notion that EBV latent genes are important for malignant cell growth. While the EBV-encoded nuclear antigen-1 (EBNA-1) and latent membrane protein-2A (LMP-2A) are critical, the EBNA-leader proteins, EBNA-2, EBNA-3A, EBNA-3C and LMP-1, are individually essential for in vitro transformation of primary B cells to lymphoblastoid cell lines. EBV-encoded RNAs and EBNA-3Bs are dispensable. In this review, the roles of EBV latent genes are summarized.

Euphorbia fischeriana extract reactivates latent HIV through nuclear factor-κB pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of Euphorbia fischeriana extract on latent HIV reactivation and the pathway involved in this process and discuss the value of Euphorbia fischeriana extract in eliminating HIV.</p><p><b>METHODS</b>Fresh tissues of Euphorbia fischeriana root were crushed into powder after quick freezing with liquid nitrogen and extracted with acetone followed by a three-day vacuum freeze-drying for dehydration of the extract. The extract (EFE) was separated using RP-C18 column with high-performance liquid chromatography (HPLC) and identified with mass spectrometry (MS). The activity of reactivated latent HIV was analyzed by fluorescence-activated cell sorting in a J-Lat 10.6 cell model treated with EFE (50 µg/mL) for 24 h, using TNF-α (10 ng/mL) as the positive control. The effect of a NF-κB pathway inhibitor (Bay 11-7082) on EFE activity was tested. The changes in P65 expression in the cell nuclei within 2 h and HIV protein p24 expression within 24 h were analyzed by Western blotting in cells treated with EFE.</p><p><b>RESULTS</b>EFE was obtained by one-step acetone extraction, and the concentration of prostratin in the extract was around 0.53 mmol/L. About 50% of the cells showed HIV reactivation after treatment with 50 µg/mL EFE for 24 h accompanied by a significantly increased p24 expression. The activity of EFE in reactivating latent HIV was inhibited by Bay 11-7082 in a concentration-dependent manner, and p65 accumulation was detected in the cell nuclei within 2 h.</p><p><b>CONCLUSION</b>EFE we obtained contains the active compounds of prostratin and its analogues and shows a strong capacity to reactivate latent HIV through classical NF-κB pathway.</p>

Epstein Barr virus-associated lymphoproliferative diseases: the virus as a therapeutic target

Epstein Barr virus (EBV)-associated lymphoproliferative diseases (LPDs) express all EBV latent antigens (type III latency) in immunodeficient patients and limited antigens (type I and II latencies) in immunocompetent patients. Post-transplantation lymphoproliferative disease (PTLD) is the prototype exhibiting type III EBV latency. Although EBV antigens are highly immunogenic, PTLD cell proliferation remains unchecked because of the underlying immunosuppression. The restoration of anti-EBV immunity by EBV-specific T cells of either autologous or allogeneic origin has been shown to be safe and effective in PTLDs. Cellular therapy can be improved by establishing a bank of human leukocyte antigen-characterized allogeneic EBV-specific T cells. In EBV+ LPDs exhibiting type I and II latencies, the use of EBV-specific T cells is more limited, although the safety and efficacy of this therapy have also been demonstrated. The therapeutic role of EBV-specific T cells in EBV+ LPDs needs to be critically reappraised with the advent of monoclonal antibodies and other targeted therapy. Another strategy involves the use of epigenetic approaches to induce EBV to undergo lytic proliferation when expression of the viral thymidine kinase renders host tumor cells susceptible to the cytotoxic effects of ganciclovir. Finally, the prophylactic use of antiviral drugs to prevent EBV reactivation may decrease the occurrence of EBV+ LPDs.

Reservorios del virus de inmunodeficiencia humana tipo 1 (VIH-1): mecanismos de latencia y estrategias terapéuticas / Human immunodeficiency virus type 1 (HIV-1) reservoirs: mechanisms of latency and therapeutic strategies Eliuth

El VIH-1 puede establecer una infección latente en varios tipos de células que constituyen sus reservorios y permiten su mantenimiento en el hospedero indefinidamente. Los principales reservorios del VIH-1 son los linfocitos T CD4 en reposo, aunque también pueden serlo los monocitos/macrófagos, las células dendríticas y otras células. Varios mecanismos contribuyen al establecimiento y mantenimiento de la latencia en estas células, entre ellos la interferencia transcripcional, la baja disponibilidad de factores de transcripción, la condensación de la cromatina y algunos microARN que bloquean la traducción viral. El conocimiento de estos mecanismos es crucial para el desarrollo de nuevas terapias que puedan eliminar el virus del cuerpo y llegar a una posible cura de esta infección.

Human immunodeficiency virus type 1 (HIV-1) can establish a latent infection in different kinds of cells, which constitute the reservoirs for the virus and allow its maintenance in the body indefinitely. The main reservoirs of HIV-1 are resting CD4+ T cells, although other cells, among them monocytes/macrophages, and dendritic cells may also act as such. Different mechanisms contribute to the establishment and maintenance of latency in those cells, among them: transcriptional interference, low availability of transcription factors, chromatin condensation, and some microRNA that block viral translation. Knowledge of these mechanisms is crucial for the development of new drugs that may eliminate the virus from the body and lead to a cure.