Early Reverse Transcription Is Essential for Productive Foamy Virus Infection

BACKGROUND: Although viral RNA constitutes the majority of nucleic acids packaged in virions, a late occurring step of reverse transcription leads to the presence of infectious viral cDNA in foamy virus particles. This peculiarity distinguishes them from the rest of the retroviral family. PRINCIPAL FINDINGS: To evaluate the respective contribution of these viral nucleic acids in the replication of foamy viruses, their fate was studied by real-time PCR and RT-PCR early after infection, in the presence or in the absence of AZT. We found that an early reverse transcription step, which occurs during the first hours post-entry, is absolutely required for productive infection. Remarkably, sensitivity to AZT can be counteracted by increasing the multiplicity of infection (moi). We also show that 2-LTR circular viral DNA, which appears as soon as four hours post-infection, is transcriptionally competent. CONCLUSION: Taken together, our data demonstrate that an early reverse transcription process, which takes place soon after viral entry, is indispensable for infectivity of FVs at low moi, when the amount of DNA-containing particles is not sufficient to lead to a productive infection. This study demonstrates a key role of the packaged viral RNA in the foamy virus infection, suggesting that the replication of this virus can be achieved by involving either viral DNA or RNA genome, depending on the condition of infection

Motives for the Acceptance of the Social Sharing of Positive and Negative Emotions and Perceived Motives of the Narrator for Sharing the Emotional Episode

This study aimed to highlight the individual’s motives for accepting the social sharing of emotions of a person as well as the motives perceived by the individual for the other’s sharing. The 81 participants first retrieved an actual situation from their memory in which they had listened to a person who had experienced a negative or positive emotional episode and, secondly, they freely described these motives. A semantic categorization showed that the motives for accepting a person’s social sharing are mainly the desire to provide the narrator with proof of social links and support; the perceived motives for the other’s social sharing are mainly a supposed need to vent and to strengthen social links. The discussion makes suggestions for future studies in the field of emotion communication

Integrase and integration: biochemical activities of HIV-1 integrase

Integration of retroviral DNA is an obligatory step of retrovirus replication because proviral DNA is the template for productive infection. Integrase, a retroviral enzyme, catalyses integration. The process of integration can be divided into two sequential reactions. The first one, named 3'-processing, corresponds to a specific endonucleolytic reaction which prepares the viral DNA extremities to be competent for the subsequent covalent insertion, named strand transfer, into the host cell genome by a trans-esterification reaction. Recently, a novel specific activity of the full length integrase was reported, in vitro, by our group for two retroviral integrases (HIV-1 and PFV-1). This activity of internal cleavage occurs at a specific palindromic sequence mimicking the LTR-LTR junction described into the 2-LTR circles which are peculiar viral DNA forms found during viral infection. Moreover, recent studies demonstrated the existence of a weak palindromic consensus found at the integration sites. Taken together, these data underline the propensity of retroviral integrases for binding symmetrical sequences and give perspectives for targeting specific sequences used for gene therapy

A novel function for spumaretrovirus integrase: an early requirement for integrase-mediated cleavage of 2 LTR circles

Retroviral integration is central to viral persistence and pathogenesis, cancer as well as host genome evolution. However, it is unclear why integration appears essential for retrovirus production, especially given the abundance and transcriptional potential of non-integrated viral genomes. The involvement of retroviral endonuclease, also called integrase (IN), in replication steps apart from integration has been proposed, but is usually considered to be accessory. We observe here that integration of a retrovirus from the spumavirus family depends mainly on the quantity of viral DNA produced. Moreover, we found that IN directly participates to linear DNA production from 2-LTR circles by specifically cleaving the conserved palindromic sequence found at LTR-LTR junctions. These results challenge the prevailing view that integrase essential function is to catalyze retroviral DNA integration. Integrase activity upstream of this step, by controlling linear DNA production, is sufficient to explain the absolute requirement for this enzyme. The novel role of IN over 2-LTR circle junctions accounts for the pleiotropic effects observed in cells infected with IN mutants. It may explain why 1) 2-LTR circles accumulate in vivo in mutants carrying a defective IN while their linear and integrated DNA pools decrease; 2) why both LTRs are processed in a concerted manner. It also resolves the original puzzle concerning the integration of spumaretroviruses. More generally, it suggests to reassess 2-LTR circles as functional intermediates in the retrovirus cycle and to reconsider the idea that formation of the integrated provirus is an essential step of retrovirus production

Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import

<p>Abstract</p> <p>Background</p> <p>Integration of human immunodeficiency virus type 1 (HIV-1) into a host cell chromosome is an essential step under the control of the viral integrase (IN). Although this enzyme is necessary and sufficient to catalyze the integration reaction <it>in vitro</it>, cellular cofactors are involved in the process <it>in vivo</it>. The chromatin-associated factor LEDGF/p75 interacts with IN and promotes integration to transcription units of the host genome. HIV-1 IN also binds the karyopherin TNPO3, however the significance of this interaction during viral replication remains to be explored.</p> <p>Results</p> <p>Here we present a functional analysis of IN mutants impaired for LEDGF/p75 and TNPO3 interaction. Among them, IN W131A and IN Q168L, that were previously identified to be deficient for LEDGF/p75 interaction, were also partially impaired for TNPO3 binding. We observed that mutations abolishing IN ability to form tetramers resulted in a severe reduction in LEDGF/p75 binding. In sharp contrast, no correlation could be found between the ability of IN to multimerize and TNPO3 interaction. Most of the mutant viruses were essentially impaired for the integration step whereas the amount of 2-LTR circles, reflecting the nuclear import of the viral DNA, was not significantly affected.</p> <p>Conclusion</p> <p>Our functional analysis of HIV-1 IN mutants reveals distinct structural basis for TNPO3 interaction and suggests that the interaction between IN and TNPO3 is not a major determinant of nuclear import but could take place at a nuclear step prior to integration.</p

5-Nitro-3-(2-(4-phenylthiazol-2-yl)hydrazineylidene)indolin-2-one derivatives inhibit HIV-1 replication by a multitarget mechanism of action

In the effort to identify and develop new HIV-1 inhibitors endowed with innovative mechanisms, we focused our attention on the possibility to target more than one viral encoded enzymatic function with a single molecule. In this respect, we have previously identified by virtual screening a new indolinone-based scaffold for dual allosteric inhibitors targeting both reverse transcriptase-associated functions: polymerase and RNase H. Pursuing with the structural optimization of these dual inhibitors, we synthesized a series of 35 new 3-[2-(4-aryl-1,3-thiazol-2-ylidene)hydrazin-1-ylidene]1-indol-2-one and 3-[3-methyl-4-arylthiazol-2-ylidene)hydrazine-1-ylidene)indolin-2-one derivatives, which maintain their dual inhibitory activity in the low micromolar range. Interestingly, compounds 1a, 3a, 10a, and 9b are able to block HIV-1 replication with EC50 &lt; 20 µM. Mechanism of action studies showed that such compounds could block HIV-1 integrase. In particular, compound 10a is the most promising for further multitarget compound development

A agricultura como catalisador para fortalecer a resiliência dos sistemas alimentares no caribe: Uma contribuição para os debates nas Américas No caminho para a cúpula sobre os sistemas alimentares das Nações Unidas 2021

Se presentan algunos desafíos claves para el desarrollo que enfrenta actualmente la agricultura regional y sugerir un marco y acciones para transformar efectivamente el sector, dentro del proceso preparatorio para la Cumbre sobre los Sistemas Alimentarios de las Naciones Unidas por celebrarse a fines de este año. Se aborda la necesidad de un abordaje integrado que enfatice la orientación de la agricultura regional hacia el aumento de su contribución al PIB; el rol de la agricultura en la promoción de una población saludable en la región; la tecnología y la innovación como componentes imprescindibles de las estrategias agrícolas; la vinculación efectiva de la agricultura regional con el turismo; y asegurar que se adopten enfoques más nuevos y más sensibles al clima en la agricultura regional.It presents some key development challenges currently facing regional agriculture and suggests a framework and actions to effectively transform the sector, within the preparatory process for the United Nations Food Systems Summit to be held later this year. The need for an integrated approach that emphasizes the orientation of regional agriculture towards increasing its contribution to GDP is addressed; the role of agriculture in promoting a healthy population in the region; technology and innovation as essential components of agricultural strategies; the effective linking of regional agriculture with tourism; and ensuring that newer, more climate-sensitive approaches are adopted in regional agriculture.Apresenta alguns dos principais desafios de desenvolvimento enfrentados atualmente pela agricultura regional e sugere uma estrutura e ações para transformar efetivamente o setor, dentro do processo preparatório para a Cúpula de Sistemas Alimentares das Nações Unidas a ser realizada ainda este ano. A necessidade de uma abordagem integrada que enfatize a orientação da agricultura regional para aumentar sua contribuição para o PIB é abordada; o papel da agricultura na promoção de uma população saudável na região; tecnologia e inovação como componentes essenciais das estratégias agrícolas; a efetiva articulação da agricultura regional com o turismo; e assegurar que abordagens mais novas e mais sensíveis ao clima sejam adotadas na agricultura regional

Inteligencia emcocional y estrés en estudiantes universitarios durante la pandemia COVID 19

La investigación tuvo como propósito determinar la relación entre inteligencia emocional y estrés, el diseño de investigación fue correlacional, se evaluó a 356 estudiantes de una universidad de Arequipa. Para la recolección de datos se utilizó el instrumento TMMS-24, el cual cuenta con tres dimensiones (percepción, comprensión y regulación emocional) y la Escala de Percepción Global de Estrés (EPGE). Se obtuvo que existe una correlación negativa baja (-.299) entre inteligencia emocional y estrés, siendo esta una relación baja (p<0,01). Así mismo, se encontró que la edad tiene relación con ambas variables; además, se obtuvo que existe asociación entre virtualidad y estrés

Indicadores financieros en instituciones de microfinanzas

Los indicadores financieros son herramientas métricas que permiten analizar el estado económico y financiero de una empresa dentro de un periodo determinado. La información se extrae directamente de los estados de la institución financiera, con la finalidad de satisfacer la necesidad de información de acuerdo con los objetivos de la empresa. Entre los indicadores más importantes, que deben tener en cuenta las instituciones de microfinanzas, están los relacionados con la liquidez, la gestión de activos, la rentabilidad y el endeudamiento. La relevancia de estos radica en la utilidad para orientar a sectores específicos que le permitan obtener mayores ganancias. Estos ratios financieros son considerados claves para medir la situación actual, eficiencia y evolución de las microfinancieras, ya que ofrecen información objetiva como soporte para tomar decisiones a corto y largo plazo de forma acertada y oportuna. En este sentido, con el propósito de lograr una revisión sistemática del tema, en el primer capítulo, se definen los indicadores financieros y se describe su evolución durante la historia, así como las ventajas y desventajas de su uso, destacando a los más importantes en las microfinanzas. En el segundo capítulo, se detallan los métodos de la evaluación crediticia (cualitativo y cuantitativo) y los principales indicadores financieros involucrados en la concesión de un crédito (modelo credit scoring). En el tercer capítulo, se expone sobre la gestión financiera y las variables de impacto. Para ello, se analiza los modelos económicos con la finalidad de identificar cuáles son las variables que influyen en las microfinanzas. En el cuarto capítulo, se determinará la valoración de los indicadores financieros, entre ellos, el índice de rentabilidad, solvencia, endeudamiento, prueba ácida y liquidez. Finalmente, se evidenciará la importancia de su uso para la toma de decisiones en las instituciones financieras. Además, se examinará el valor de cada indicador para reconocer, ponderar y evaluar su utilidad en una empresa.Financial ratios are metric instruments that allow analyzing the economic and financial status of a company over a given period of time. The information is obtained directly from the financial institution's statement with the aim of satisfying the need for information in accordance with the company's objectives. Among the most important indicators that microfinance institutions must consider are those related to liquidity, asset management, profitability and indebtedness. The relevance of these ratios is based on their usefulness in targeting specific sectors that lead to higher profits. Furthermore, they are considered essential to measure the current situation, efficiency and evolution of microfinance institutions since they offer unbiased information as support for making short and long term decisions in an accurate and opportune manner. In this context, in order to achieve a systematic review of the subject, in the first chapter financial indicators are defined and their evolution throughout history is described, as well as the advantages and disadvantages of their use, emphasizing the most important ones in microfinance. In the second chapter, the methods of credit evaluation (qualitative and quantitative) and the main financial indicators involved in granting a loan (credit scoring model) are detailed. In the third chapter, financial management and impact variables are explained. To this end, economic models are analyzed in order to identify the variables that have an influence on microfinance. In the fourth chapter, the valuation of financial indicators will be determined, including the profitability index, solvency, indebtedness, acid test and liquidity. Finally, the importance of their use for decision making in financial institutions will be demonstrated. Moreover, the value of each indicator will be examined in order to recognize, weigh and evaluate its relevance in a company.Trabajo de Suficiencia Profesiona