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The tailwater from wastewater treatment plants serves as an important water resource in arid regions, alleviating the conflict between supply and demand. However, the effects of different tailwater discharge proportions on microbial community dynamics remain unclear. In this study, we investigated the effects of different tailwater discharge proportions on the water quality and microbial community characteristics of sediments in receiving water bodies under controlled conditions (WF-1, WF-2, WF-3, WF-4, and WF-5, containing 0% tailwater + 100% natural water, 25% tailwater + 75% natural water, 50% tailwater + 50% natural water, 75% tailwater + 25% natural water, and 100% tailwater + 0% natural water, respectively). Microbial co-occurrence networks and structural equation model were used to unveil the relationship between microbial communities and their shaping factors. Results showed that distinct microbial community compositions were found in the sediments with low- (< 50%) and high- (> 50%) proportions of tailwater. Specifically, WCHB1-41 and g_4-29-1, which are involved in organic degradation-related functions, were the key genera in the high-proportion cluster. A total of 21 taxa were more abundant in the low-proportion (< 50%) cluster than that in high-proportion (> 50%). Moreover, higher modularity was observed in the low-proportion. Total phosphorus directly affected while ammonia nitrogen indirectly affected the microbial community structure. Our findings support the distinct heterogeneity of microbial communities driven by tailwater discharge in receiving water bodies, and further confirmed that high-proportion tailwater depletes sensitive microbial communities, which may be avoided through scientific management.
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Sedimentos Geológicos , Microbiota , Sedimentos Geológicos/microbiología , Aguas Residuales/microbiología , Microbiología del Agua , Bacterias/clasificación , Bacterias/genética , Calidad del AguaRESUMEN
Cobalt-nitrogen co-doped carbon nanotubes (Co3@NCNT-800) were synthesized via a facile and economical approach to investigate the efficient degradation of organic pollutants in aqueous environments. This material demonstrated high catalytic efficiency in the degradation of carbamazepine (CBZ) in the presence of peroxymonosulfate (PMS). The experimental data revealed that at a neutral pH of 7 and an initial CBZ concentration of 20 mg/L, the application of Co3@NCNT-800 at 0.2 g/L facilitated a degradation rate of 64.7% within 60 min. Mechanistic investigations indicated that the presence of pyridinic nitrogen and cobalt species enhanced the generation of reactive oxygen species. Radical scavenging assays and electron spin resonance spectroscopy confirmed that radical and nonradical pathways contributed to CBZ degradation, with the nonradical mechanism being predominant. This research presents the development of a novel PMS catalyst, synthesized through an efficient and stable method, which provides a cost-effective solution for the remediation of organic contaminants in water.
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Nanotubos de Carbono , Peróxidos , Benzodiazepinas , Carbamazepina , Cobalto , Nitrógeno , AguaRESUMEN
This study aimed to apply finite element analysis to evaluate the effects of pile materials with different elastic moduli and cement materials on the stress distribution between the remaining tooth tissue and cryptic fracture defects. A three-dimensional finite element model was established for 20 maxillary first molars with hidden fissures and mesial tongue-tip defects. Two levels of hidden cracks and three types of pile and adhesive materials were used in the design. The stress distribution and maximum stress peak in the remaining tooth tissue and crack defects were determined by simulating the normal bite, maximum bite, and lateral movement forces. When titanium posts, zinc phosphate binders, and porcelain crowns were used to repair the two types of deep cracked teeth, the maximum principal stress at the crack and dentin was the smallest. As the crack depth increased, the maximum principal stress of the residual dentin and crack defects increased.
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Coronas , Técnica de Perno Muñón , Análisis de Elementos Finitos , Materiales Dentales , Diente Molar , Estrés Mecánico , Análisis del Estrés Dental , DentinaRESUMEN
Purpose: Enhanced recovery after surgery (ERAS) protocols not only positively affect gastrointestinal surgery outcomes but may also increase the risk of some complications. This meta-analysis was conducted to assess the impact of ERAS on the recovery and complications following gastrointestinal surgery. Materials and Methods: Studies published before December 2022 were retrieved from the following databases, EMBASE, PubMed, Cochrane Library, and Web of Science, without limitations of language or race. The endpoints included lung infection, surgical site infection, postoperative ileus, length of hospitalization, urinary tract infection, readmission, anastomotic leakage, and C-reactive protein serum levels. Results: A total of 23 studies were included. The results of the meta-analysis revealed that there was a decrease in incidence of the lung infection (risk ratio = 0.46, 95% confidence interval 0.27-0.74, P = .002) and postoperative length of hospitalization (P < .00001). However, ERAS protocol groups had higher readmission rates, nausea, and vomiting. There was no significant difference in the incidence of anastomotic leakage, ileus, surgical site infection, and urinary tract infection between the experimental and control groups. Conclusions: ERAS protocols can reduce the risk of postoperative lung infections, shorten hospital stays, and expedite patient recovery. Furthermore, ERAS protocols are not associated with serious complications following gastrointestinal surgeries.
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Neoplasias Colorrectales , Recuperación Mejorada Después de la Cirugía , Ileus , Infecciones Urinarias , Humanos , Fuga Anastomótica , Gastrectomía , Ileus/etiología , Ileus/prevención & control , Infección de la Herida QuirúrgicaRESUMEN
Coal mine water is usually recycled as supplementary water for aquatic ecosystems in arid and semiarid mining regions of China. To ensure ecosystem health, the coal mine water is rigorously treated using several processes, including reverse osmosis, to meet surface water quality standards. However, the potential environmental impacts of this management pattern on the ecological function of receiving water bodies are unclear. In this study, we built several microcosm water ecosystems to simulate the receiving water bodies. High-quality treated coal mine drainage was mixed into the model water bodies at different concentrations, and the sediment bacterial community response and functional changes were systematically investigated. The results showed that the high-quality coal mine drainage could still shape bacterial taxonomic diversity, community composition and structure, with a concentration threshold of approximately 50%. Moreover, both the Mantel test and the structural equation model indicated that the salinity fluctuation caused by the receiving of coal mine drainage was the primary factor shaping the bacterial communities. 10 core taxa in the molecular ecological network influenced by coal mine drainage were identified, with the most critical taxa being patescibacteria and g_Geothermobacter. Furthermore, the pathway of carbohydrate metabolism as well as signaling molecules and interactions was up-regulated, whereas amino acid metabolism showed the opposite trend. All results suggested that the complex physical-chemical and biochemical processes in water ecosystems may be affected by the coal mine drainage. The bacterial community response and underlying functional changes may accelerate internal nutrient cycling, which may have a potential impact on algal bloom outbreaks.
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Ecosistema , Minería , Bacterias , China , Carbón MineralRESUMEN
This study builds a conceptual model of strategic decision-making ability that leads to entrepreneurial performance (EP) based on the two-system decision-making theory and logical analysis. An empirical approach using structural equation modeling - artificial neural network (SEM-ANN) was performed to describe the linear and nonlinear relationships in the proposed model. The empirical results reveal that strategic decision-making abilities are affected by five factors: attention, memory, thinking, emotion, and sentiment, and whose influence mechanisms and degrees are varied. Results also describe that these abilities have a positive effect on overall EP. Therefore, results suggest that businesses' strategic decision-making is usually strengthened when entrepreneurs have a clear understanding of these influencing elements, and the interaction between them leads to improved performance.
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Green development helps to balance the conflict between economic expansion, environmental protection, and green strategy decisions by tackling the issue of excessive resource utilization during regional growth. This study aims to measure the green innovation strategic decisions quality by identifying the nexus between board capital, green innovation strategic information acquisition capability, and board group Faultline. A conceptual model has been proposed and tested to verify the proposed relationship. Data collection was analyzed using structural equation modeling in AMOS 24.0. The findings indicate that board human capital (BHC) and board social capital (BSC) have a beneficial influence on the quality of green innovation strategy decision-making. The green innovation strategic information acquisition capability plays a mediating role in the relationship between the two dimensions of board capital and the green innovation strategy decision-making quality. The mediating role of green innovation strategic information acquisition capability is moderated by board group Faultline. The core significance of this study is presented.
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Citrus canker, caused by the bacterium Xanthomonas citri subsp. citri (Xcc), seriously affects fruit quality and yield, leading to significant economic losses around the world. Understanding the mechanism of Xcc virulence is important for the effective control of Xcc infection. In this report, we investigate the role of a protein named HemK in the regulation of the virulence traits of Xcc. The hemK gene was deleted in the Xcc jx-6 background, and the ΔhemK mutant phenotypically displayed significantly decreased motility, biofilm formation, extracellular enzymes, and polysaccharides production, as well as increased sensitivity to oxidative stress and high temperatures. In accordance with the role of HemK in the regulation of a variety of virulence-associated phenotypes, the deletion of hemK resulted in reduced virulence on citrus plants as well as a compromised hypersensitive response on a non-host plant, Nicotiana benthamiana. These results indicated that HemK is required for the virulence of Xcc. To characterize the regulatory effect of hemK deletion on gene expression, RNA sequencing analysis was conducted using the wild-type Xcc jx-6 strain and its isogenic ΔhemK mutant strain, grown in XVM2 medium. Comparative transcriptome analysis of these two strains revealed that hemK deletion specifically changed the expression of several virulence-related genes associated with the bacterial secretion system, chemotaxis, and quorum sensing, and the expression of various genes related to nutrient utilization including amino acid metabolism, carbohydrate metabolism, and energy metabolism. In conclusion, our results indicate that HemK plays an essential role in virulence, the regulation of virulence factor synthesis, and the nutrient utilization of Xcc.
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Citrus , Xanthomonas , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Citrus/metabolismo , Metiltransferasas/metabolismo , Nutrientes , Enfermedades de las Plantas/microbiología , Virulencia/genéticaRESUMEN
Many encapsulated bacteria use capsules to cause invasive diseases. However, it remains largely unknown how the capsules enhance bacterial virulence under in vivo infection conditions. Here we show that the capsules primarily target the liver to enhance bacterial survival at the onset of blood-borne infections. In a mouse sepsis model, the capsules enabled human pathogens Streptococcus pneumoniae and Escherichia coli to circumvent the recognition of liver-resident macrophage Kupffer cells (KCs) in a capsular serotype-dependent manner. In contrast to effective capture of acapsular bacteria by KCs, the encapsulated bacteria are partially (low-virulence types) or completely (high-virulence types) "untouchable" for KCs. We finally identified the asialoglycoprotein receptor (ASGR) as the first known capsule receptor on KCs to recognize the low-virulence serotype-7F and -14 pneumococcal capsules. Our data identify the molecular interplay between the capsules and KCs as a master controller of the fate and virulence of encapsulated bacteria, and suggest that the interplay is targetable for therapeutic control of septic infections.
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Macrófagos del Hígado , Infecciones Neumocócicas , Animales , Cápsulas Bacterianas , Cápsulas , Hígado , Ratones , Streptococcus pneumoniae , VirulenciaRESUMEN
Women entrepreneurs are significant contributors to the economic development of any country and their role becomes more vital in improving the economic condition of developing countries. This highlights the important role of women-owned small and medium enterprises (SMEs) and their entrepreneurial success. Therefore, the current study extends the entrepreneurship literature by examining the effects of factors like personality traits (PT), motivation and commitment (MC), availability of financial resources (AFR), and government support (GS) on entrepreneurial success (ES) of women-owned SMEs. Using a purposive sampling technique data from 255 women-owned SMEs were collected. A multi-analytical approach was employed to analyze the data. The Structural equation modeling (SEM) results indicated that PT, MC, AFR, and GS have a direct effect of ES whereas MC also mediated the link between PT and ES, and the results reveal that in presence of MC the effects of PT on ES become more significant. SEM results revealed that PT and AFR are the most important factors related to entrepreneurial success. On the contrary, ANN analysis revealed that "motivation and commitment" is the most influencing factor. These findings can guide business practitioners and policymakers in the envisioned strategy formulation to encourage women entrepreneurs who can contribute to their country's sustainable economic growth.
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The paper uses the panel smooth conversion fractional-order system model to divide the mechanism of financial development in high-tech industries into two systems. At the same time, the article uses a continuous state to connect these two extreme situations to investigate the nonlinear characteristics of linear feedback control that inhibit the impact of financial development on high-tech industries. Studies have shown that financial development under a low system has a significant role in promoting high-tech industries. On the other hand, financial development under the high-level system has a restraining effect on high-tech industries. There are dual-threshold characteristics between the scale of financial development and the development of high-tech industries. Firstly, the scale of financial development should be controlled within [0.553, 0.840]. Secondly, there is a single threshold between the level of financial development and the development of high-tech industries, and the level of financial development should be controlled within 0.756.
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Industrias , RetroalimentaciónRESUMEN
Reductive dechlorination, an efficient pathway for complete removal of organic chlorinated pollutants (OCPs), is commonly reported to be coupled to oxidation of methane (CH4) or methanogenesis in anaerobic environments. However, the relationship between dechlorination and CH4-associated bioprocesses is unclear. Based on the hypothesis that CH4 supplementation could facilitate OCP dechlorination, we investigated the role of CH4-associated bioprocesses in the self-purification of flooded lindane-spiked paddy soils. Four treatments were conducted for up to 28 days: sterilized soil (S), sterilized soil + CH4 (SC), non-sterilized soil (NS), and non-sterilized soil + CH4 (NSC). Results indicated that both sterilization and addition of CH4 promoted lindane degradation and CH4 emissions in the flooded paddy soils. In the NS treatment, lindane had the lowest degradation rate when CH4 emissions were barely detected; while in the SC treatment, lindane had the highest degradation rate when CH4 achieved its highest emissions from anaerobic soil. Also, sterilization led to microbial diversity loss and functional recession, but increased ferrous ion [Fe(II)] concentrations compared to non-sterilized soils. Methanogenic communities and mcrA gene recovered faster than the majority of microorganisms (e.g., Fe bacteria, Bdellovibrionaceae, Rhizobiaceae, Dehalogenimonas) or functional genes (e.g., Dhc, Geo, narG, nirS). Collectively, we assume the enhanced removal of lindane may partly be due to both abiotic dechlorination promoted by chemical Fe redox processes and methanogenesis-derived biotic dechlorination. Revealing the coupling between dechlorination and CH4-associated bioprocesses is helpful to resolve both pollution remediation and mitigation of CH4 emissions in anaerobic contaminated sites.
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Hexaclorociclohexano , Contaminantes del Suelo , Metano , Suelo , Microbiología del Suelo , Contaminantes del Suelo/análisisRESUMEN
In this paper, environmental friendly magnetic composite adsorbent (MSAL), exhibited excellent adsorption capacity for lead ions in the solution, was successfully prepared using two non-biologically toxic materials including L-cysteine and sodium alginate. Batch experiments were carried out to discuss the influences of different parameters like pH, adsorbent dosing, initial concentration and contact time on adsorption performance. Results showed sorption process followed by pseudo-second-order kinetic model and Langmuir isotherm model, which suggested the adsorption was limited by the chemical process dominated by the molecular layer. Based on Langmuir isotherm model, the maximum Pb(â ¡) adsorption capacity was about 330 mg/g, which was better than a large amount of other lead adsorbents. Various analytical methods, such as SEM-EDS, FTIR, VSM, TGA, XPS and Zeta potential, were applied to characterize the performance of this adsorbent as well as exploring the adsorption mechanism. Characterization results found this adsorbent exhibited a large contact area, good thermal stability, sufficient adsorption sites and excellent magnetic responsiveness. It also has been found that the adsorption mechanism mainly included ion exchange and chelation between amino, carboxyl and lead ions. After 5 cycles, the adsorption capacity decreased from 98.04% to 87.40% and still maintained at high level. The average iron ions concentration in the adsorbed solution sample or in the regeneration solution were 0.34 mg/L and 0.15 mg/L. Overall, all above results imply that MSAL is a promising reusable adsorbent for removing Pb(â ¡) in solution.
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Plomo/análisis , Nanopartículas de Magnetita/química , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodos , Adsorción , Alginatos/química , Cisteína/química , Óxido Ferrosoférrico/química , Concentración de Iones de Hidrógeno , Cinética , Fenómenos Magnéticos , Propiedades de SuperficieRESUMEN
Viruses rely on host chaperone network to support their infection. In particular, the endoplasmic reticulum (ER) resident chaperones play key roles in synthesizing and processing viral proteins. Influx of a large amount of foreign proteins exhausts the folding capacity in ER and triggers the unfolded protein response (UPR). A fully-executed UPR comprises signaling pathways that induce ER folding chaperones, increase protein degradation, block new protein synthesis and may eventually activate apoptosis, presenting both opportunities and threats to the virus. Here, we define a role of the MHV-68M1 gene in differential modulation of UPR pathways to enhance ER chaperone production. Ectopic expression of M1 markedly induces ER chaperone genes and expansion of ER. The M1 protein accumulates in ER during infection and this localization is indispensable for its function, suggesting M1 acts from the ER. We found that M1 protein selectively induces the chaperon-producing pathways (IRE1, ATF6) while, interestingly, sparing the translation-blocking arm (PERK). We identified, for the first time, a viral factor capable of selectively intervening the initiation of ER stress signaling to induce chaperon production. This finding provides a unique opportunity of using viral protein as a tool to define the activation mechanisms of individual UPR pathways.
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Retículo Endoplásmico/metabolismo , Infecciones por Herpesviridae/metabolismo , Infecciones por Herpesviridae/virología , Chaperonas Moleculares/biosíntesis , Rhadinovirus/fisiología , Factor de Transcripción Activador 6/metabolismo , Animales , Modelos Animales de Enfermedad , Retículo Endoplásmico/virología , Expresión Génica , Infecciones por Herpesviridae/genética , Proteínas de la Membrana/metabolismo , Ratones , Chaperonas Moleculares/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal , Respuesta de Proteína DesplegadaRESUMEN
Combination chemotherapy with multiple drugs has been widely applied to cancer treatment owing to enhanced efficacy and reduced drug resistance. For drug combination experiment analysis, response surface modeling has been commonly adopted. In this paper, we introduce a Hill-based global response surface model and provide an application of the model to a 512-run drug combination experiment with three chemicals, namely AG490, U0126, and indirubin-3 ' -monoxime (I-3-M), on lung cancer cells. The results demonstrate generally improved goodness of fit of our model from the traditional polynomial model, as well as the original Hill model on the basis of fixed-ratio drug combinations. We identify different dose-effect patterns between normal and cancer cells on the basis of our model, which indicates the potential effectiveness of the drug combination in cancer treatment. Meanwhile, drug interactions are analyzed both qualitatively and quantitatively. The distinct interaction patterns between U0126 and I-3-M on two types of cells uncovered by the model could be a further indicator of the efficacy of the drug combination.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Interpretación Estadística de Datos , Neoplasias Pulmonares/tratamiento farmacológico , Modelos Estadísticos , Adenosina Trifosfato/metabolismo , Butadienos/administración & dosificación , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Humanos , Indoles/administración & dosificación , Neoplasias Pulmonares/metabolismo , Nitrilos/administración & dosificación , Oximas/administración & dosificación , Tirfostinos/administración & dosificaciónRESUMEN
The ability to control cellular functions can bring about many developments in basic biological research and its applications. The presence of multiple signals, internal as well as externally imposed, introduces several challenges for controlling cellular functions. Additionally the lack of clear understanding of the cellular signaling network limits our ability to infer the responses to a number of signals. This work investigates the control of Kaposi's sarcoma-associated herpesvirus reactivation upon treatment with a combination of multiple signals. We utilize mathematical model-based as well as experiment-based approaches to achieve the desired goals of maximizing virus reactivation. The results show that appropriately selected control signals can induce virus lytic gene expression about ten folds higher than a single drug; these results were validated by comparing the results of the two approaches, and experimentally using multiple assays. Additionally, we have quantitatively analyzed potential interactions between the used combinations of drugs. Some of these interactions were consistent with existing literature, and new interactions emerged and warrant further studies. The work presents a general method that can be used to quantitatively and systematically study multi-signal induced responses. It enables optimization of combinations to achieve desired responses. It also allows identifying critical nodes mediating the multi-signal induced responses. The concept and the approach used in this work will be directly applicable to other diseases such as AIDS and cancer.
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Herpesvirus Humano 8/metabolismo , Activación Viral/fisiología , Interacciones Farmacológicas , Modelos Teóricos , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Cells constantly sense many internal and environmental signals and respond through their complex signaling network, leading to particular biological outcomes. However, a systematic characterization and optimization of multi-signal responses remains a pressing challenge to traditional experimental approaches due to the arising complexity associated with the increasing number of signals and their intensities. RESULTS: We established and validated a data-driven mathematical approach to systematically characterize signal-response relationships. Our results demonstrate how mathematical learning algorithms can enable systematic characterization of multi-signal induced biological activities. The proposed approach enables identification of input combinations that can result in desired biological responses. In retrospect, the results show that, unlike a single drug, a properly chosen combination of drugs can lead to a significant difference in the responses of different cell types, increasing the differential targeting of certain combinations. The successful validation of identified combinations demonstrates the power of this approach. Moreover, the approach enables examining the efficacy of all lower order mixtures of the tested signals. The approach also enables identification of system-level signaling interactions between the applied signals. Many of the signaling interactions identified were consistent with the literature, and other unknown interactions emerged. CONCLUSIONS: This approach can facilitate development of systems biology and optimal drug combination therapies for cancer and other diseases and for understanding key interactions within the cellular network upon treatment with multiple signals.
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Biología de Sistemas/métodos , Algoritmos , Línea Celular Tumoral , Biología Computacional/métodos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Modelos Biológicos , Modelos Teóricos , Neoplasias/tratamiento farmacológico , Transducción de Señal , Programas InformáticosRESUMEN
Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL) cells are predominantly infected with latent Kaposi's sarcoma-associated herpesvirus (KSHV), presenting a barrier to the destruction of tumor cells. Latent KSHV can be reactivated to undergo lytic replication. Here we report that in PEL cells, oxidative stress induced by upregulated reactive oxygen species (ROS) can lead to KSHV reactivation or cell death. ROS are upregulated by NF-κB inhibition and are required for subsequent KSHV reactivation. Disruption of the intracellular redox balance through depletion of the antioxidant glutathione or inhibition of the antioxidant enzyme catalase also induces KSHV reactivation, suggesting that hydrogen peroxide induces reactivation. In addition, p38 signaling is required for KSHV reactivation induced by ROS. Furthermore, treatment of PEL cells with a higher concentration of the NF-κB inhibitor than that used for inducing KSHV reactivation further upregulates ROS and induces massive cell death. ROS, but not p38 signaling, are required for PEL cell death induced by NF-κB inhibition as well as by glutathione depletion. Importantly, anticancer drugs, such as cisplatin and arsenic trioxide, also induce KSHV reactivation and PEL cell death in a ROS-dependent manner. Our study thus establishes a critical role for ROS and oxidative stress in the regulation of KSHV reactivation and PEL cell death. Disrupting the cellular redox balance may be a potential strategy for treating KSHV-associated lymphoma.
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Muerte Celular , Herpesvirus Humano 8/patogenicidad , Linfocitos/virología , Estrés Oxidativo , Activación Viral , Catalasa/antagonistas & inhibidores , Células Cultivadas , Glutatión/antagonistas & inhibidores , Humanos , Linfoma de Efusión Primaria/virología , FN-kappa B/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Kaposi's sarcoma-associated herpesvirus (KSHV) is linked with Kaposi's sarcoma and lymphomas. The pathogenesis of KSHV depends on the balance between two phases of the viral cycle: latency and lytic replication. In this study, we report that KSHV-encoded microRNAs (miRNAs) function as regulators by maintaining viral latency and inhibiting viral lytic replication. MiRNAs are short, noncoding, small RNAs that post-transcriptionally regulate the expression of messenger RNAs. Of the 12 viral miRNAs expressed in latent KSHV-infected cells, we observed that expression of miR-K3 can suppress both viral lytic replication and gene expression. Further experiments indicate that miR-K3 can regulate viral latency by targeting nuclear factor I/B. Nuclear factor I/B can activate the promoter of the viral immediate-early transactivator replication and transcription activator (RTA), and depletion of nuclear factor I/B by short hairpin RNAs had similar effects on the viral life cycle to those of miR-K3. Our results suggest a role for KSHV miRNAs in regulating the viral life cycle.
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Replicación del ADN , Herpesvirus Humano 8/genética , MicroARNs/metabolismo , ARN Mensajero/metabolismo , Latencia del Virus , Línea Celular , ADN Viral/biosíntesis , Regulación Viral de la Expresión Génica , Herpesvirus Humano 8/fisiología , Humanos , MicroARNs/genética , Regiones Promotoras Genéticas , Sarcoma de Kaposi/fisiopatología , Transactivadores/metabolismo , Replicación ViralRESUMEN
Cellular signalling pathways are critical in regulating the balance between latency and lytic replication of herpesviruses. Here, we investigated the effect of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway on replication of two gamma-2 herpesviruses, murine gammaherpesvirus-68 (MHV-68) and human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus (HHV-8/KSHV). We found that de novo infection of MHV-68 induced PI3K-dependent Akt activation and the lytic replication of MHV-68 was enhanced by inhibiting the PI3K-Akt pathway with both chemical inhibitors and RNA interference technology. Inhibiting the activity of Akt using Akt inhibitor VIII also facilitated the reactivation of KSHV from latency. Both lytic replication and latency depend on the activity of viral transactivator RTA and we further show that the activity of RTA is increased by reducing Akt1 expression. The data suggest that the PI3K-Akt pathway suppresses the activity of RTA and thereby contributes to the maintenance of viral latency and promotes tumorigenesis.