Hepatitis B virus X gene differentially modulates subgenotype F1b and F4 replication

Hepatitis B virus (HBV) is classified into ten genotypes and numerous subgenotypes (sgt). In particular, sgt F1b and sgt F4, native of Latin America, have been associated with differences in clinical and virological characteristics. Hepatitis B virus X protein (HBx) is a multifunctional regulatory protein associated with the modulation of viral transcription and replication. In this work, we analyzed the role of the X gene and the encoded X protein in sgtF1b and sgtF4 replication. Transfection with HBx deficient genomes revealed remarkable differences in the replicative capacity of sgtF1b and sgtF4 mutants. The silencing of HBx increased sgtF1b X(-) transcription and replication by more than 2.5 fold compared to the wild type variant, while it decreased sgtF4 X(-) transcription and replication by more than 3 fold. Trans-complementation of HBx restore sgtF1b and sgtF4 wild type transcription and replication levels. In addition, transfection with chimeric variants, carrying wild type (F1b/XF4 and F4/XF1b) or mutated (F1b/X(-)F4 and F4/X(-)F1b) X gene of one sgt in the backbone of the other sgt, showed that the nucleotide sequence of the X gene, that includes regulatory elements that modulate pgRNA transcription, was responsible for the disparity observed between sgtF1b X(-) and sgtF4 X(-). These results showed that sgtF1b and sgtF4 X gene play a central role in regulating HBV transcription and replication, which eventually lead to a common purpose, to reach wild type replication levels of sgtF1b and sgtF4 viruses.Fil: Elizalde, Maria Mercedes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Speroni, Micaela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Campos, Rodolfo Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; ArgentinaFil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Antiviral activity of flavonoids present in aerial parts of Marcetia taxifolia against Hepatitis B virus, Poliovirus, and Herpes Simplex Virus in vitro

Marcetia taxifolia is a neotropical plant present in South America and it has been evaluated in several biological models due to the presence of active metabolites. Nevertheless, there is a limited quantity of studies related to the antiviral activity of the compounds present in this genus. In our work, the antiviral effect of the compounds isolated from the aerial parts of Marcetia taxifolia was evaluated against Hepatitis B virus (HBV), Herpes Simplex Virus type 1 (HSV-1), and Poliovirus type 1 (PV-1). The cytopathic effect and viral quantification by qPCR were determined as indicative of antiviral activity. Our data show that myricetin rhamnoside (MyrG), myricetin-3-α-O-ramnosil (1→6)-α-galactoside (MyrGG), 5,3'-dihydroxy-3,6,7,8,4’-pentamethoxyflavone (PMF), 5-hydroxy-3,6,7,3',4'pentamethoxyflavone (PMF-OH) had antiviral activity without cytotoxic effects. The methoxyflavones PMF and PMF-OH were the most active compounds, showing an antiviral effect against all the evaluated viruses. Computational studies showed that these compounds could interact with the Reverse Transcriptase. Altogether, these results suggest that the flavonoids (related to myricetin and methoxyflavones) are the main antiviral compounds present in the aerial parts of Marcetia taxifolia. Furthermore, our results showed that the methoxyflavones have a broad antiviral activity, which represents an opportunity to evaluate these flavonoids as lead molecules to develop new antiviral compounds

Genetic history of Hepatitis C virus in Venezuela: high diversity and long time of evolution of HCV genotype 2

Background: The subtype diversity of the hepatitis C virus (HCV) genotypes is unknown in Venezuela. Methodology/Principal Findings: Partial sequencing of the NS5B region was performed in 310 isolates circulating in patients from 1995 to 2007. In the samples collected between 2005 and 2007, HCV genotype 1 (G1) was the most common genotype (63%), composed as expected of mainly G1a and G1b. G2 was the second most common genotype (33%), being G2a almost absent and G2j the most frequent subtype. Sequence analysis of the core region confirmed the subtype assignment performed within the NS5b region in 63 isolates. The complete genome sequence of G2j was obtained. G2j has been described in France, Canada and Burkina Fasso, but it was not found in Martinique, where several subtypes of G2 circulate in the general population. Bayesian coalescence analysis indicated a most recent common ancestor (MRCA) of G2j around 1785, before the introduction of G1b (1869) and G1a (1922). While HCV G1a and G1b experienced a growth reduction since 1990, coincident with the time when blood testing was implemented in Venezuela, HCV G2j did not seem to reach growth equilibrium during this period. Conclusions/Significance: Assuming the introduction of G2j from Africa during the slave trade, the high frequency of G2j found in Venezuela could suggest: 1- the introduction of African ethnic groups different from the ones introduced to Martinique or 2- the occurrence of a founder effect. This study represents an in-depth analysis of the subtype diversity of HCV in Venezuela, which is still unexplored in the Americas and deserves further studies.Fil: Sulbarán, Maria Z.. Instituto Venezolano de Investigaciones Cientificas; VenezuelaFil: Di Lello, Federico Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Sulbarán, Yoneira. Instituto Venezolano de Investigaciones Cientificas; VenezuelaFil: Cosson, Clarisa. Instituto Venezolano de Investigaciones Cientificas; VenezuelaFil: Loureiro, Carmen. Instituto Venezolano de Investigaciones Cientificas; VenezuelaFil: Rangel, Héctor R.. Instituto Venezolano de Investigaciones Cientificas; VenezuelaFil: Cantaloube, Jean F.. Etablissement Français du Sang Alpes-Méditerranée. Unité Emergence et Co-évolution virale; FranciaFil: Campos, Rodolfo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Moratorio, Gonzalo. Universidad de la Republica; Uruguay. Instituto Pasteur de Montevideo; UruguayFil: Cristina, Juan. Universidad de la Republica; UruguayFil: Pujol, Flor H.. Instituto Venezolano de Investigaciones Cientificas; Venezuel

Territorios sustentables en contexto de pandemia

La obra ofrece trabajos que brindan un conocimiento científico sobre el impacto de la pandemia en la salud, la economía, el ambiente y los territorios y se plantean desafíos para hacer más sostenible la vida en las ciudades y en el campo para insertarse y poder competir a nivel global

Emergence of a square chaotic attractor through the collision of heteroclinic orbits

In this work we introduce a square chaotic attractor based on the collision of two heteroclinic orbits. Before the collision, the system presents the coexistence of two double scroll attractors that are generated via piecewise linear (PWL) systems that deal with two saddle-foci equilibria of different classes, i.e. the dimensions of the unstable and stable manifolds of one of the equilibrium points are one and two, respectively, and vice versa for the unstable and stable manifolds associated with the second equilibrium point. The new class is constructed based on the existence of a heteroclinic loop by linear affine systems with two saddle-focus equilibrium points of different types. The chaotic behavior of the proposed system is tested by the maximum Lyapunov exponent and the 0–1 chaos test. This new class of PWL dynamical systems exhibits different behaviors and allows the generation of different basins of attraction for the coexistence of two or more attractors. Therefore, a mechanism to establish bistability is provided and how it can be controlled (i.e. bistability annihilation) via varying system’s parameters is demonstrated

Long‐term evolution of hepatitis B virus genotype F: strong association between viral diversification and the prehistoric settlement of Central and South America

The genotype F (HBV-F) is an autochthonous Native American strain of the hepatitis B virus. In this study, we reconstruct the HBV-F long-term evolution under a hypothesis of co-divergence with humans in Central and South America, since their entry into the region 14.5-16 thousand years ago. The Bayesian phylogeographic reconstruction supported a virus-host co-expansion, however, two evolutionary scenarios would have been present. Whereas subgenotype F1 spread along a Pacific coastal route and would have evolved associated with Central American and Andean cultures from the west of the continent, subgenotypes F2-F6 spread along the Atlantic coastline and inner pathways associated with communities inhabiting the tropical forest lowlands. Then, we propose a model for HBV-F evolution in which the selection of differential biological characteristics in these two main groups would be related to their evolution in host populations with different genetic backgrounds and dissimilar demographic conditions.Fil: Mojsiejczuk, Laura Noelia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Torres, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Campos, Rodolfo Héctor. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentin

Bistable behavior via switching dissipative systems with unstable dynamics and its electronic design

"In this work we present a design of a bistable system and its electronic circuit which is generated by a switching system. The switching system is comprised by dissipative subsystems with unstable dynamics based on the jerk equation. For this system with unstable dynamics, it is necessary to use a switching control law in order to change the equilibrium point of the linear part and get bounded trajectories. Also the dynamics of the piecewise linear (PWL) system is illustrated by numerical simulations to depict the bistable states. We present an easy electronic design of the proposed system by employing resistors, capacitors and comparators, to exhibit the capability to generate bistable behavior.

A class of Chua-like systems with only two saddle-foci of different type

"Since the reported Chua’s system, several generalizations of this system have been presented, these approaches include new equilibria in order to obtain three or more scrolls in the attractor. One of these generalizations requires at least the same number of saddle-foci with local two-dimensional unstable manifolds as the desired number of scrolls. In this work, we present the generation of a double-scroll chaotic attractor called Chua-like system. Once that an equilibrium point has been removed from the Chua’s system and there are only two saddle-foci of different class, i.e. the dimension of one of the local unstable manifolds is one while the other is of dimension two. The new class is constructed based on the existence of a heteroclinic loop by linear affine systems with two saddle-focus equilibrium points of different type. Furthermore, the chaotic behavior of the proposed system is tested by the maximum Lyapunov exponent and the 0 — 1 chaos test.

Evaluación del crecimiento, factor de conversión de alimento y calidad del agua del cultivo de trucha arco iris (Oncorhynchus mykiss) en un sistema cerrado

The growth up of rainbow trout (Oncorhynchus mykiss) in a reuse reconditioning water system was carried out with the porpose to measure the growth rates, food convertion ratio and water quality. Ninety five trout with an average weight of 98.24 +- 18.89 grams and total length of 22.47 +- 0.95cm were used. These organisms were introduced in 5.6m3 circular tnaks, each one with a density of 3 ind/m3. The tanks flow of water maintained constant in 21 min-1 and the fishes were fed three times a day (3% of biomass) with a commercial diet containing 41.9 +- 0.13% preotein and 12.08 +- 0.12% lipids. Biomentrics parameters were measured every fouteen days and calculated the instantaneous growth rate (IGR), the specific growth rate (Gu), and Food Convertion Ratio (FCR). Also ammonia, toxic ammonia, nitrites, nitrates, dissolved oxygen and pH were registered along the experiment. The results shiwed after 39 days of culture, the trout increased to 140g in average weight and 26.4cm in average length. IGR was 0.02276, Gu of 11.67% day -1 and 1.4 of FCR. Temperature and pH (19.8 °C and 9.03 respectively) were constant along the experimet. Ammonia, nitrites and nitrates (0.01, 0.01 and 0.12 mg -1), and toxic ammonia presented higher variation, but not affected the survival and growth rates. The gained weight daily was of 3.6g day -1, that was a higher value compared with others results reported in related works, in spite of the higher average temperature registered along the experiment.Se cultivó la trucha arco iris (Oncorhynchus mykiss) en un sistema de recirculación y reacondicionamiento de agua, con el objeto de medir la tasa de crecimiento, el factor de conversión de alimento y las condiciones de calidad del agua del sistema. Se utilizaron 95 truchas con un peso promedio de 98.24 +- 18.89g y una longitud promedio de 22.47 +- 0.95cm, las cuales fueron introducidas en seis estanques circulares de 5.6 m3 cada uno a una densidad de 3 ind/m3. El flujo de agua fue de 21 min-1 y los peces se alimentaron tres veces al día con una dieta comercial balanceada con 41.9 +- 0.13% de proteína y 12.08 +- 0.12% de lípidos, suministrando al 3% de la biomasa por estanque al día. Se tomaron registros catorcenales de longitud toral y peso para calcular la tasa inastantánea de crecimiento (TIC), la tasa específica de crecimiento (Gu) y el factor de conversión de alimento (FCA). También se registraron periódicamente el amonio total, amonio tóxico, nitritos, nitratos, oxígeno disuelto y pH. Los resultados indicaron que, después de 39 días de cultivo, los organismo en promedio incrementaron hasta 140g en peso y 26.4cm de longitud. La TIC fue de 0.02276, la Gu de 11.67% día -1 y el FCA de 1.4. LA temperatura y el pH (19.8 °C y 9.03 respectivamente) se mantuvieron constatntes a lo largo del experimento. El nitrógeno amoniacal, nitritos y nítratos, (0.01, 0.01 y 0.12 mg), así como la fracción tóxica del amonio no variaron y se mantuvieron dentro del intervalo de tolerancia de esta especie. El crecimiento en este sistema fue de 3.6g día -1, que es superior al reportado en otros trabajos a pesar de que el promedio de temperatura se consideró elevadoo para esta especie