Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB.
Hepatitis C virus (HCV) and the malaria parasite Plasmodium use the membrane protein CD81 to invade human liver cells. Here we mapped 33 host protein interactions of CD81 in primary human liver and hepatoma cells using high-resolution quantitative proteomics. In the CD81 protein network, we identified five proteins which are HCV entry factors or facilitators including epidermal growth factor receptor (EGFR). Notably, we discovered calpain-5 (CAPN5) and the ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene B (CBLB) to form a complex with CD81 and support HCV entry. CAPN5 and CBLB were required for a post-binding and pre-replication step in the HCV life cycle. Knockout of CAPN5 and CBLB reduced susceptibility to all tested HCV genotypes, but not to other enveloped viruses such as vesicular stomatitis virus and human coronavirus. Furthermore, Plasmodium sporozoites relied on a distinct set of CD81 interaction partners for liver cell entry. Our findings reveal a comprehensive CD81 network in human liver cells and show that HCV and Plasmodium highjack selective CD81 interactions, including CAPN5 and CBLB for HCV, to invade cells.
Janina Bruening, Lisa Lasswitz, Pia Banse, Sina Kahl, Carine Marinach, Florian W Vondran, Lars Kaderali, Olivier Silvie, Thomas Pietschmann, Felix Meissner, Gisa Gerold
Biology (General), Immunologic diseases. Allergy
Hepatitis C Virus Resistance to Carbohydrate-Binding Agents.
Carbohydrate binding agents (CBAs), including natural lectins, are more and more considered as broad-spectrum antivirals. These molecules are able to directly inhibit many viruses such as Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Dengue Virus, Ebola Virus or Severe Acute Respiratory Syndrome Coronavirus through binding to envelope protein N-glycans. In the case of HIV, it has been shown that CBAs select for mutant viruses with N-glycosylation site deletions which are more sensitive to neutralizing antibodies. In this study we aimed at evaluating the HCV resistance to CBAs in vitro. HCV was cultivated in the presence of increasing Galanthus nivalis agglutinin (GNA), Cyanovirin-N, Concanavalin-A or Griffithsin concentrations, during more than eight weeks. At the end of lectin exposure, the genome of the isolated strains was sequenced and several potential resistance mutations in the E1E2 envelope glycoproteins were identified. The effect of these mutations on viral fitness as well as on sensitivity to inhibition by lectins, soluble CD81 or the 3/11 neutralizing antibody was assessed. Surprisingly, none of these mutations, alone or in combination, conferred resistance to CBAs. In contrast, we observed that some mutants were more sensitive to 3/11 or CD81-LEL inhibition. Additionally, several mutations were identified in the Core and the non-structural proteins. Thus, our results suggest that in contrast to HIV, HCV resistance to CBAs is not directly conferred by mutations in the envelope protein genes but could occur through an indirect mechanism involving mutations in other viral proteins. Further investigations are needed to completely elucidate the underlying mechanisms.
Laure Izquierdo, Catarina Oliveira, Carole Fournier, Véronique Descamps, Virginie Morel, Jean Dubuisson, Etienne Brochot, Catherine Francois, Sandrine Castelain, Gilles Duverlie, François Helle
Hepatobiliary and Pancreatic Manifestations of Coronavirus Disease 2019
Pancreatic, hepatobiliary, Severe Acute Respiratory Syndrome Coronavirus 2, corona virus disease 2019
Coronavirus disease 2019 (COVID-19) is a new infectious disease that has spread rapidly throughout the world. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the Coronaviridae family. Though the pulmonary involvement is a major cause of morbidity and mortality, involvement of the gastrointestinal tract, liver, and pancreas has been explained in these patients. The literature is rapidly changing because of influx of new information with every passage of time. The most common hepatic presentation is mild elevation of aspartate transaminase and alanine transaminase, which does not require specific treatment. Occasionally, patients can have severe liver injury. Because of underlying predisposing factors such as diabetes mellitus, hypertension, and obesity, patients with nonalcoholic liver disease may be at risk of severe disease. Patients with decompensated liver disease may also be vulnerable to severe disease. Behavior of SARS-CoV-2 in patients with chronic hepatitis B and C, autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cirrhosis is yet to be seen. The prevalence and severity of COVID-19 patients with the aforementioned diseases may be different. The effect of SARS-CoV-2 on an underlying liver disease is not known. COVID-19 may complicate the peritransplant period and throw new challenges in these patients. Drugs used to treat severe COVID-19 may cause liver injury and may have an effect on the underlying disease activity. Both hepatic and pancreatic involvement is related to the severity of COVID-19 disease. Serum amylase and lipase levels may be elevated in patients with severe COVID-19 disease. The involvement of pancreatic islet cells may lead to deranged blood sugar levels and potentially predispose to future diabetes mellitus. There are many unknown facts that will unfold with the passage of time.
Diseases of the digestive system. Gastroenterology
Hepatology in the COVID Era: Another C Virus, again Challenging the Liver
Paula Peixe, Filipe Calinas, Rui Tato Marinho
GE: Portuguese Journal of Gastroenterology
Hepatotoxicidad en el paciente crítico: El hígado bajo agresión aguda grave Hepatotoxicity in the critically ill patient: The liver under an acute severe insult
Agreesión, Hígado, Injury, Liver, disfunción, dysfunction
El hígado desempeña un papel fundamental en el metabolismo de la mayoría de los nutrientes pues es un órgano principalmente metabólico y lleva a cabo una serie de procesos fisiológicos y bioquímicos relacionables con el metabolismo proteico y energético. Consideramos al tracto gastrointestinal como una pieza clave en el desarrollo del Fallo o Disfunción Multiorgánica (DMO) como consecuencia de una pérdida de su función de barrera (alteración de la permeabilidad) secundaria a hipoxia frente a toxinas, bioproductos y ocasionalmente bacterias intraluminales, siendo uno de los principales mecanismos fisiopatogénicos el insuficiente flujo de sangre a los órganos esplácnicos. La disfunción hepática y/o alteración en los test de función hepática es un evento común entre los pacientes críticos. Puede estar originada por una cirrosis previa o por causas más inmediatas de insuficiencia- fallo hepático como la sepsis, drogas, transplante hepático o alguna de las múltiples etiologías de la hepatitis.The liver plays an essential role in the metabolism of most of the nutrients since it is a mainly metabolic organ carrying out a series of physiological and metabolic processes related with protein and energy metabolism. The intestinal tract is considered a key element in the development of Multiorgan Dysfunction (MOD) or failure by loosing its barrier function (impaired permeability) against toxins, bio-products and occsaionally intraluminal bacteria secondary to hypoxia, one of the main pathopysiogenic mechanisms being the insufficient blood flow to splacnic organs. Liver dysfunction and/or impairment of liver function test are a common event in critically ill patients. They may be due to previous liver cirrhosis or to more immedite causes of liver failure such as sepsis, drugs, liver transplant or any of the multiple etiologies for hepatitis.
A. García de Lorenzo y Mateos, J. A. Rodríguez Montes
Nutritional diseases. Deficiency diseases
Herança e gênero entre agricultores familiares Inheritance and Gender Identity Among Brazilian Farming Families
Agricultura Familiar, Social reproduction, farming family, gender identities, herança, identidades de género, inheritance, reprodução social
Entender as lógicas de transmissão do patrimônio familiar, particularmente no caso da terra, levando-se conta as diferenças de gênero, exige identificar os distintos papéis reservados ao homem e à mulher na dinâmica de reprodução social. A compreensão de tais lógicas distintas requer que investiguemos os diferentes signficados do patimônio territorial em cada contexto social e cultural. Embora a herança seja baseada na noção de consanguinidade, as regras costumeiras não reconhecem os mesmos direitos para todos os filhos. É precisamente sobre essas diferenças de que trataremos nesse artigo, particularmente no que se diz respeito às distintas práticas derivadas das identidades de gênero. Buscar-se-á entender a lógica das diferentes formas de transmitir a herança e sua relação com a reprodução social de famílias de agricultores familiares em duas regiões distintas: no municipio de Nova Pádua, na região de influência de Caxias do Sul, no estado do Rio Grande do Sul, e na região serrana do estado do Rio de Janeiro, município de Nova FriburgoTo understand the rules by which family estates are transmitted among farming families, particularly in the case of land and taking into account gender differences, it is necessary to identify the distinct roles reserved to men and women in the dynamics of social reproduction. The understanding of these distinct logics requires the investigation of the different meanings that the territorial patrimony itself has in each social and cultural context. Although inheritance is based on the notion of shared blood, common law rules do not recognize the same rights for all children. It is precisely these differences that we will deal with in this article, particularly in respect to those differences derived from gender identity. We will be seeking to understand the logic of different forms of transmitting inheritances and their relationship with the social reproduction of farming families in two different regions: in southern Brazil (state of Rio Grande do Sul), among descendants of Italian colonists, and in the mountainous region of the state of Rio de Janeiro, among descendants of Swiss and German colonists.
Herbal Medicine for the Treatment of Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Herbal Medicine, covid-19, coronavirus disease, systematic review, Complementary and alternative medicine
Background: The coronavirus disease 2019 (COVID-19) pandemic has caused a worldwide outbreak of respiratory illness. This review aims to evaluate the effectiveness and adverse events of herbal medicines for the treatment of COVID-19. Methods: Twelve databases were searched through 12 May 2020. Randomized controlled trials (RCTs) and quasi-RCTs assessing the effects of herbal medicines for the treatment of COVID-19 were eligible. The study selection and data extraction were performed by two independent reviewers. The Cochrane risk of bias tool was used for the assessment of the risk of bias in all included RCTs. Mean differences (MDs), risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and the effect sizes of the studies were pooled. Results: Seven RCTs with a total of 855 patients were included. All included trials compared the combined therapy of herbal medicine with Western medicine to Western medicine alone. The combined therapy significantly improved the total effective rate (RR 1.23, 95% CI 1.13 to 1.34, p < 0.001), cough symptom disappearance rate (RR 1.45, 95% CI 1.12 to 1.89, p = 0.005), and sputum production symptom disappearance rate (RR 1.73, 95% CI 1.19 to 2.50, p = 0.004). Beneficial effects of the combined therapy were also seen in TCM syndrome score of cough (MD −1.18, 95% CI −1.34 to −1.03, p < 0.001), fever (MD −0.62, 95% CI −0.79 to −0.45, p < 0.001), dry and sore throat (MD −0.83, 95% CI −1.45 to −0.20, p = 0.009), and fatigue (MD −0.60, 95% CI −1.04 to −0.17, p = 0.007). The overall risk of bias of the included studies was unclear. No serious adverse events were reported. Conclusion: Significant effects of the combined therapy of herbal medicine with Western medicine were found, and revealed the potential role of herbal medicine in treating COVID-19. More high-quality RCTs are needed to further validate the effectiveness and adverse events of herbal medicine in the treatment of COVID-19.
Hye Won Lee, Myeong Soo Lee, Lin Ang, Eunhye Song
Herbicides in the Irrigated Rice Production System in Babahoyo, Ecuador, Using Neutrosophic Statistics
Tukey’s test, herbicides, neutrosophic statistics, rice, weed
Rice cultivation is of great importance worldwide, due to its nutritional properties and becauseit is part of many plates of the inhabitants of all continents. Weeds are part of the factors that affect riceproduction, which is why it is necessary to apply herbicides, including the modality of the presence ofherbicides in irrigation. This paper aims to carry out a statistical study on the effectiveness of differenttreatments to eliminate the weeds of the INDIA SFL 11 rice variety in Babahoyo, Ecuador. The evaluationof some results of the treatments was carried out visually based on both weed control and herbicidetoxicity by using linguistic terms that are associated with an indeterminate scale of percentages, wherethe data are given in the form of intervals and not in crisp values. Additionally other seven criteria arealso utilized. Thus, we decided to apply neutrosophic statistics as a study tool for this problem. Neutrosophic statistics extends classical statistics theory to the framework of neutrosophy, where intervals areused instead of analyzing crisp values. Specifically, Tukey's test is applied in comparing some data inform of intervals that denotes the imprecision of the obtained measurement
Dalton Cadena-Piedrahita, Salomón Helfgott-Lerner, Andrés Drouet-Candel, Fernando Cobos-Mora, Nessar Rojas-Jorgge
Mathematics, Electronic computers. Computer science
Herd immunity against COVID-19: is it enough to stop a second wave?
immunity, covid-19, second wave, herd immunity, past-infection
covid-19, SARS-CoV-2, Indonesia, herd immunity
Herd immunity or herd effect is a phenomenon that occurs in groups of people who are resistant to disease. The purpose of conducting this research is to predict the number of cumulative cases of COVID-19 in Indonesia. Covid-19 cases in Indonesia on April 6, 2020, were 2235 cases spread in 34 Provinces. As many as 2491 cases in Indonesia, there were 192 patients recovered (including those treated, so they have natural antibodies in the end) while the total who died was 209 people. It is assumed that around 13% of the total cases have natural antibodies. This is also the case with SARS-CoV-2 and may explain why some individuals (perhaps those most recently able to recover from seasonal coronavirus infections) have asymptomatic infections. Finally, the theoretical concept of increasing herd immunity in pandemic and epidemic cases in Indonesia which aims to control COVID-19 still needs to be reviewed because it is seen from the mortality data that CFR COVID-19 is predicted to be around 8.39% of the population in Indonesia where the risk of death still available. The best alternative is to do a healthy lifestyle, social distancing, and waiting for the vaccine to be found.