Dengue viruses(DENV)have spread throughout the world and pose a huge threat to human life.The most widespread serotype is type 2 DENV(DENV 2),which has no specific treatment.NS2B-NS3 protease plays a pivotal role in D...Dengue viruses(DENV)have spread throughout the world and pose a huge threat to human life.The most widespread serotype is type 2 DENV(DENV 2),which has no specific treatment.NS2B-NS3 protease plays a pivotal role in DENV replication because of its function in cleavage of the viral polyprotein;thus,it is considered a promising target for antiviral discovery.In this study,we developed a high-throughput screening system based on the NS2B-NS3 protease to identify candidates from an FDA-approved drug library.Eltrombopag was screened out of 3273 drugs,and demonstrated inhibition on DENV 2 at the micromolar level in vitro,significantly reducing viral loads in the targeted organs of challenged mice following intraperitoneal injection.Further mechanistic analysis showed that eltrombopag allosterically binds to the DENV 2 NS2B-NS3 protease in a reversible,noncompetitive manner,therefore inhibiting DENV 2 at the post-infection stage.In addition,eltrombopag inhibited the NS2B-NS3 proteases of DENV 4 and Zika virus,suggesting its potential as a broadspectrum antiviral agent.This study repurposed eltrombopag as a promising antiviral agent against DENV,providing an alternative for antiviral development against flaviviruses.展开更多
Mosquito-borne flaviviruses,such as Zika virus(ZIKV)and dengue virus(DENV),cause diverse severe clinical manifestations including fever,rash,hepatitis,arthralgia,and congenital anomalies.Here,we identified a host fact...Mosquito-borne flaviviruses,such as Zika virus(ZIKV)and dengue virus(DENV),cause diverse severe clinical manifestations including fever,rash,hepatitis,arthralgia,and congenital anomalies.Here,we identified a host factor,the adaptor protein complex 1 gamma 1 subunit(AP1G1),which plays an important role in both ZIKV and dengue virus 2(DENV2)infections.We explored the role of AP1G1 in ZIKV and DENV2 infections using CRISPR/Cas9 gene editing technology and RNA interference(RNAi)techniques.Knockout or silencing of AP1G1 decreases the replication of ZIKV and DENV2 in multiple human cell lines.Intriguingly,depletion of AP1G1 results in a significant reduction in ZIKV at an early stage,but decreases DENV2 replication levels during the late stage,suggesting that AP1G1 plays distinct roles in the infection by ZIKV and DENV2.Furthermore,we determined that AP1G1 mediates ZIKV-endosomal membrane fusion through inhibitor experiments and fluorescence labeling assays.Mechanistically,we found that AP1G1 exerts its pro-viral effect through binding to the ZIKV envelope glycoprotein(E protein).This interaction promotes the fusion of viral and endosomal membranes,during which the ZIKV genomic RNAs are released from the endosome into the cytoplasm,a process that facilitates viral replication.However,for DENV2 infection,AP1G1 primarily affects its viral RNA replication stage,rather than the fusion of virus-endosomal membrane.Taken together,our work demonstrates that AP1G1 plays a pro-viral role in both ZIKV and DENV2 infections via distinct mechanisms,highlighting its potential as a therapeutic target for antiviral strategies.展开更多
Dengue virus(DENV)is a positive-sense single-stranded RNA virus belonging to the genus Flavivirus within the Flaviviridae family.Four serotypes,DENV 1-4,are distributed globally[1].Hanoi metropolitan city is an endemi...Dengue virus(DENV)is a positive-sense single-stranded RNA virus belonging to the genus Flavivirus within the Flaviviridae family.Four serotypes,DENV 1-4,are distributed globally[1].Hanoi metropolitan city is an endemic hotspot for DENV transmission in Vietnam[2,3].The largest outbreak occurred in 2017,with more than 36000 cases and 7 deaths reported,causing by all four serotypes with the predominance of DENV1,following by DENV2[4,5].During the following dengue season,we collected 390 blood and serum samples from 197 hospitalized patients in a national hospital in Hanoi city,Northern Vietnam to identify the circulating DENV serotypes responsible for the 2018-2019 outbreak.展开更多
The causative agent for dengue is dengue virus(DENV),with humans and mosquitoes serving as vectors.The DENV(family=Flaviviridae)is a positive-stranded RNA virus with four serotypes,DENV-1,DENV-2,DENV-3,and DENV-4.As o...The causative agent for dengue is dengue virus(DENV),with humans and mosquitoes serving as vectors.The DENV(family=Flaviviridae)is a positive-stranded RNA virus with four serotypes,DENV-1,DENV-2,DENV-3,and DENV-4.As of 2023,the disease had been reported in 80 countries with over 6.5 million cases and 7300 mortalities since then.Despite the concerning incidence and prevalence of this disease,less attention is given to the development of therapeutic remedies and preventive alternatives.The search for new antiviral bioactive compounds is therefore important and urgent.Marine organisms have been a source of diverse bioactive natural products.The large marine biodiversity and the structural diversity of their specialized metabolites provide an explorative opportunity for the discovery of novel antiviral specialized metabolites.Reported marine natural products with anti-DENV activities include fucoidan,scequinadoline A,indole derivatives,and others.Nevertheless,marine organisms are still largely underexplored as sources of antiviral drugs.With advances in metabolomics and computational screening,we may discover additional marine natural products to help with dengue treatment.展开更多
Dengue virus(DENV)is a mosquito-borne pathogen responsible for a spectrum of illnesses,including dengue fever,dengue hemorrhagic fever,and dengue shock syndrome.Nearly half of the global population is at risk of DENV ...Dengue virus(DENV)is a mosquito-borne pathogen responsible for a spectrum of illnesses,including dengue fever,dengue hemorrhagic fever,and dengue shock syndrome.Nearly half of the global population is at risk of DENV infection,making it a pressing public health issue worldwide.The limited cross-protection among the four DENV serotypes(DENV1-4)and the phenomenon of antibody-dependent enhancement(ADE)have posed significant challenges to the development of effective dengue vaccines.Furthermore,there are currently no specific antiviral treatments available.This review provides an overview of DENV's key characteristics,clinical manifestations,and recent advancements in antiviral drug development-including the repurposing of approved drugs,peptidebased antiviral agents,therapeutic antibodies,natural products with antiviral potential,and host factor inhibitors-aiming to offer critical insights to inform strategies for managing and preventing dengue outbreaks.展开更多
The current recommendation to avoid non-steroidal anti-inflammatory drugs(NSAIDs)in the management of dengue virus disease(DVD)is scientifically considered of very low to low certainty,despite being widely adopted wor...The current recommendation to avoid non-steroidal anti-inflammatory drugs(NSAIDs)in the management of dengue virus disease(DVD)is scientifically considered of very low to low certainty,despite being widely adopted worldwide.The same recommendation,initially made during the coronavirus disease 2019(COVID-19)pandemic,was subsequently proven incorrect.In this clinical report,we present evidence,for the first time globally,from a real-life practice that NSAIDs may actually be lifesaving in the early management of DVD as they have proved to be in COVID-19.Moreover,we propose that the personalized immunemodulatory Kelleni’s protocol,which includes nitazoxanide as a key component,can be safely and effectively used to manage various separate or concomitant viral infections and co-infections,including DVD.Importantly,this article contributes to the current medical knowledge in the global pursuit of a safe and effective broad-spectrum antiviral protocol that can be used to early manage multiple highly infectious viruses.However,it’s crucial that sufficiently powered controlled randomized clinical trials be conducted to thoroughly assess and evaluate the safety of NSAIDs in the early management of DVD as well as the efficacy of nitazoxanide with or without NSAIDs in its management.展开更多
Background and Objectives: Dengue is an arbovirosis caused by the dengue virus with 04 serotypes. The aim of the study was to characterise the four serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) of the dengue virus cir...Background and Objectives: Dengue is an arbovirosis caused by the dengue virus with 04 serotypes. The aim of the study was to characterise the four serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) of the dengue virus circulating in Ouagadougou, Burkina Faso. Methods: This was a descriptive analytical study that included 2833 patients and was carried out from January 2021 to December 2022. Rapid diagnosis of dengue was performed using the “Dengue Duo (AgNS1/IgM/IgG)” kit (SD Bioline, Korea). Viral RNA was extracted using the QIAGEN RNA RNeasy Plus Mini Kit (Quiagen, Germany) and virus serotypes were identified using the DENGUE Real-TM Genotype PCR kit (Sacace biotechnologies, Italy). Platelet counts were also performed using the XN-1500 Sysmex. Results: The prevalence of acute infections (NS1Ag positive) by TDR was 5.7% (162/2833), with the peak of dengue virus infection occurring between October and November. On the other hand, the AgNS1+ samples tested by RT-PCR were 53.7% positive for dengue virus;this shows the extent of probable cross-reactions with rapid diagnostic tests and false positives. Serotype 1 accounted for 52.6%, 28.4% had serotype 3, 16.8% had serotype 2 and 2.1% had serotype 4. We found cases of co-infection with DENV-1 and DENV-2 in two patients, co-infection with DENV-1 and DENV-3 in three patients, co-infection with DENV-1 and DENV-4 in one patient, co-infection with DENV-3 and DENV-4 in one patient and co-infection with three serotypes, DENV-1, DENV-2 and DENV-3 in one patient. Conclusion: The study showed that all four serotypes of the dengue virus were circulating in Ouagadougou. Serotype 1 was predominant.展开更多
Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significa...Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.展开更多
Objective:To evaluate the in vitro activities of the ethyl acetate(EA) fraction of Houttuynia cordata(H.cordata) Thunb.(Saururaceae) and three of its constituent flavonoids(quercetin.quercitrin and rutin) against muri...Objective:To evaluate the in vitro activities of the ethyl acetate(EA) fraction of Houttuynia cordata(H.cordata) Thunb.(Saururaceae) and three of its constituent flavonoids(quercetin.quercitrin and rutin) against murine coronavirus and dengue virus(DENV).Methods:The antiviral activities of various concentrations of the EA fraction of H.cordata and flavonoids were assessed using virus neutralization tests against mouse hepatitis virus(MHV) and DENV type 2(DENV-2).Cinanserin hydrochloride was also tested against MHV.The EA fraction of H.cordata was tested for acute oral toxicity in C57BL/6 mice.Results:The EA fraction of H.cordata inhibited viral infectivity up to 6 d.Cinanserin hydrochloride was able to inhibit MHV for only 2 d.The 50%inhibitory concentrations(IC_(50)) of the EA fraction of H.cordata added before the viral adsorption stage were 0.98 μg/mL for MHV and 7.50 μg/mL for DENV-2with absence of cytotoxicity.The mice fed with the EA fraction up to 2 000 mg/kg did not induce any signs of acute toxicity,with normal histological features of major organs.Certain flavonoids exhibited comparatively weaker antiviral activity,notably quercetin which could inhibit both MHV and DENV-2.This was followed by quercitrin which could inhibit DENV-2but not MHV,whereas rutin did not exert any inhibitory effect on either virus.When quercetin was combined with quercitrin,enhancement of anti-DENV-2 activity and reduced cytotoxicity were observed.However,the synergistic efficacy of the flavonoid combination was still less than that of the EA fraction.Conclusions:The compounds in H.cordata contribute to the superior antiviral efficacy of the EA fraction which lacked cytotoxicity in vitro and acute toxicity in vim.H.cordata has much potential for the development of antiviral agents against coronavirus and dengue infections.展开更多
Dengue virus(DENV) belongs to the genus Flavivirus of the family Flaviviridae and it is primarily transmitted via Aedes aegypti and Aedes albopictus mosquitoes. The life cycle of DENV includes attachment, endocytosis,...Dengue virus(DENV) belongs to the genus Flavivirus of the family Flaviviridae and it is primarily transmitted via Aedes aegypti and Aedes albopictus mosquitoes. The life cycle of DENV includes attachment, endocytosis, protein translation, RNA synthesis, assembly, egress, and maturation.Recent researches have indicated that a variety of host factors, including cellular proteins and micro RNAs, positively or negatively regulate the DENV replication process. This review summarizes the latest findings(from 2014 to 2016) in the identification of the host factors involved in the DENV life cycle and Dengue infection.展开更多
Dengue virus infection has become a global threat affecting around 100 countries in the world.Currently,there is no licensed antiviral agent available against dengue.Thus,there is a strong need to develop therapeutic ...Dengue virus infection has become a global threat affecting around 100 countries in the world.Currently,there is no licensed antiviral agent available against dengue.Thus,there is a strong need to develop therapeutic strategies that can tackle this life threatening disease.RNA interference is an important and effective gene silencing process which degrades targeted RNA by a sequence specific process.Several studies have been conducted during the last decade to evaluate the efficiency of siRNA in inhibiting dengue virus replication.This review summarizes siRNAs as a therapeutic approach against dengue virus serotypes and concludes that siRNAs against virus and host genes can be next generation treatment of dengue virus infection.展开更多
Dengue virus(DENV)infection is a worldwide public health threat.To date,the knowledge about the pathogenesis and progression of DENV infection is still limited.Combining global profiling based on proteomic analysis to...Dengue virus(DENV)infection is a worldwide public health threat.To date,the knowledge about the pathogenesis and progression of DENV infection is still limited.Combining global profiling based on proteomic analysis together with functional verification analysis is a powerful strategy to investigate the interplay between the virus and host cells.In the present study,quantitative proteomics has been applied to evaluate host responses(as indicated by altered proteins and modifications)in human cells(using K562 cell line)upon DENV-2 infection,as DENV-2 spreads most widely among all DENV serotypes.Comparative analysis was performed to define differentially expressed proteins in the infected cells compared to the mock-control,and it revealed critical pathogen-induced changes covering a broad spectrum of host cellular compartments and processes.We also discovered more dramatic changes(>20%,160 regulated phosphoproteins)in protein phosphorylation compared to protein expression(14%,321 regulated proteins).Most of these proteins/phosphoproteins were involved in transcription regulation,RNA splicing and processing,immune system,cellular response to stimulus,and macromolecule biosynthesis.Western blot analysis was also performed to confirm the proteomic data.Potential roles of these altered proteins were discussed.The present study provides valuable large-scale protein-related information for elucidating the functional emphasis of host cell proteins and their post-translational modifications in virus infection,and also provides insight and protein evidence for understanding the general pathogenesis and pathology of DENV.展开更多
The Pearl River Delta,where Aedes albopictus(Ae.albopictus)is the only vector for dengue transmission,has exhibited one of the highest dengue burdens in southern China in recent decades.However,whether dengue virus(DE...The Pearl River Delta,where Aedes albopictus(Ae.albopictus)is the only vector for dengue transmission,has exhibited one of the highest dengue burdens in southern China in recent decades.However,whether dengue virus(DENV)can overwinter in Ae.albopictus in the Pearl River Delta has not been determined to date.In this study,300 field-derived Ae.albopictus mosquitoes from Guangzhou that were infected with the predominant endemic DENV-1 strain were investigated under simulated urban balcony environment from October 16,2016,to June 16,2017.The vertical transmission of DENV in the infected overwintering Ae.albopictus was analyzed.The DENV infected overwintering mosquitoes were evaluated for viral load at nine-time points using reverse transcription-quantitative PCR.The vector competence of the infected overwintering Ae.albopictus was also investigated by using suckling mice.Adult mosquitoes and larvae were found during the observation period.The vertical transmission of DENV-1 was documented.The DENV-1-positive rates between overwintering males and females had no difference.The proportion of DENV-1-positive overwintering mosquitoes decreased over time and had no difference beyond three months after the experiment.Overwintering mosquitoes can spread DENV-1 to hosts.No engorged mosquitoes at an ambient temperature below 15℃were observed.The ratio of engorged mosquitoes was positively correlated with the ambient temperature ranging from 15 to 30℃.Our results demonstrated that DENV can overwinter in Ae.albopictus in the Pearl River Delta,Ae.albopictus is the competent vector for DENV,and maintain autochthonous dengue outbreaks in the Pearl River Delta through vertical transmission.展开更多
Objective:To develop diagnostic test for detection chikungunya virus(CHIKV and Dengue virus (DENV) infection.Methods:We have performed a rapid,accurate laboratory confirmative method to simultaneously detect,quantify ...Objective:To develop diagnostic test for detection chikungunya virus(CHIKV and Dengue virus (DENV) infection.Methods:We have performed a rapid,accurate laboratory confirmative method to simultaneously detect,quantify and differentiate CHIKV and DENV infection by single-step multiplex real-time RT-PCR.Results:The assay’s sensitivity was 97.65%,specificity was 92.59% and accuracy was 95.82%when compared to conventional RT-PCR.Additionally,there was no cross-reaction between CHIKV,DENV,Japanese encephalitis virus,hepatitis C,hepatitis A or hepatitis E virus.Conclusions:This rapid and reliable assay provides a means for simultaneous early diagnosis of CHIKV and DENV in a single-step reaction.展开更多
Dengue virus(DENV) has emerged as a major virus that is spread by mosquitoes. Recently, it has spread to more than a hundred nations but continues to lack specific treatable medication. Many traditional Chinese medici...Dengue virus(DENV) has emerged as a major virus that is spread by mosquitoes. Recently, it has spread to more than a hundred nations but continues to lack specific treatable medication. Many traditional Chinese medicinal(TCM) plants are in practice for dengue fever in dengue endemic regions. These traditional medicines persevere with treatments, which modern medicines lack. The study aims to substantiate the anti-dengue potential of some traditional herbs and make them available for further studies to facilitate TCM users. Twelve TCM plants aqueous extracts were evaluated, which are described as cool herbs used for the diseases with high fever. Lead plants were established through detailed in vitro foci forming unit reduction analysis(FFURA) against all four serotypes and validated through quantitative real-time RT-PCR(q RT-PCR). Four plants potentially inhibited the virus in primary phenotypic in vitro evaluation. Two lead plants Dryopteris crassirhizoma(DC) and Morus alba(MA) were identified with half minimal inhibitory concentration(IC50) 130 and 221 μg m L^-1, respectively, while the selectivity indices(SI) were 4.21 and 4.62, respectively. Lead plants equally inhibited all four serotypes of DENV. Time-of-addition analysis suggested that, DC was active at later stages of viral replication, whereas MA was active during the early stages and even showed some prophylactic activity. Liquid chromatography-mass spectrometry(HPLC/MS) analysis revealed presence of flavonoids. DC and MA are identified as potential anti-dengue plants, active against varied stages of dengue virus replication cycle. These results may serve as the base knowledge for further investigation on their combined treatments or integrative treatment with western medicines, which may improve the overall anti-dengue activity in future.展开更多
Objective: To investigate the inhibitory effects against dengue virus serotype 2(DENV-2) by five different fractions(extracted by methanol, ethanol, benzene, chloroform and n-hexane) of Rumex dentatus, Commelina bengh...Objective: To investigate the inhibitory effects against dengue virus serotype 2(DENV-2) by five different fractions(extracted by methanol, ethanol, benzene, chloroform and n-hexane) of Rumex dentatus, Commelina benghalensis, Ajuga bracteosa and Ziziphus mauritiana, as well as their constituents(gallic acid, emodin, and isovanillic acid). Methods: All the samples were tested for cytotoxicity on baby hamster kidney cells by MTT assay and for anti-DENV-2 activity by plaque reduction neutralization assay using two DENV-2 doses(45 and 90 plaqueforming units or PFU). Results: All the samples except isovanillic acid exhibited significant prophylactic effects against DENV-2 infectivity(without cytotoxicity) when administered to cells before infection, but were not effective when given 6 h post-infection. The methanol extract of Rumex dentatus demonstrated the highest antiviral efficacy by inhibiting DENV-2 replication, with IC_(50) of 0.154 μg/mL and 0.234 μg/mL, when added before infection with 45 and 90 PFU of virus, respectively. Gallic acid also exhibited significant antiviral effects by prophylactic treatment prior to virus adsorption on cells, with IC_(50) of 0.191 μg/mL and 0.522 μg/mL at 45 and 90 PFU of DENV-2 infection, respectively. Conclusions: The highly potent activities of the extracts and constituent compounds of these plants against DENV-2 infectivity highlight their potential as targets for further research to identify novel antiviral agents against dengue.展开更多
Dengue fever, caused by dengue viruses(DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate(pV-D4...Dengue fever, caused by dengue viruses(DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate(pV-D4 ME) expressing prM-E protein of DENV serotype 4(DENV-4) was constructed, and its immunogenicity and protection were evaluated in immunocompetent BALB/c mice. The pV-D4 ME candidate vaccine induced effective humoral and cellular immunity of mice against DENV-4 in vivo when administered both at 50 μg and 5 μg through electroporation. Two weeks after receiving three immunizations, both doses of pV-D4 ME DNA were shown to confer effective protection against lethal DENV-4 challenge. Notably, at 6 months after the three immunizations, 50 μg, but not 5 μg, of pV-D4 ME could provide stable protection(100% survival rate) against DENV-4 lethal challenge without any obvious clinical signs. These results suggest that immunization with 50 μg pV-D4 ME through electroporation could confer effective and long-term protection against DENV-4, offering a promising approach for development of a novel DNA vaccine against DENVs.展开更多
Dengue virus(DENV)is one of the most important arboviral pathogens in the tropics and subtropics,and nearly one-third of the world's population is at risk of infection.The transmission of DENV involves a sylvatic ...Dengue virus(DENV)is one of the most important arboviral pathogens in the tropics and subtropics,and nearly one-third of the world's population is at risk of infection.The transmission of DENV involves a sylvatic cycle between nonhuman primates(NHP)and Aedes genus mosquitoes,and an endemic cycle between human hosts and predominantly Aedes aegypti.DENV belongs to the genus Flavivirus of the family Flaviviridae and consists of four antigenically distinct serotypes(DENV-1-4).Phylogenetic analyses of DENV have revealed its origin,epidemiology,and the drivers that determine its molecular evolution in nature.This review discusses how phyloge-netic research has improved our understanding of DENV evolution and how it affects viral ecology and improved our ability to analyze and predict future DENV emergence.展开更多
Objective: To describe the clinical manifestation of patient with severe dengue, to identify the serotypes and genotypes of dengue viruses(DENV) which concurrently infecting the patient, and to explore the possible re...Objective: To describe the clinical manifestation of patient with severe dengue, to identify the serotypes and genotypes of dengue viruses(DENV) which concurrently infecting the patient, and to explore the possible relationship of severe dengue with the concurrent infection of DENV. Methods: Dengue diagnosis was performed using NS1 antigen detection and Ig G/Ig M ELISA. Standard clinical and laboratory examinations were performed to obtain the clinical and hematological data. DENV concurrent infections were detected and confirmed using RT-PCR and DENV Envelope gene sequencing. Phylogenetic analyses were performed to determine the genotypes of the viruses. Results: The patient was classified as having severe dengue characterized by severe plasma leakage, hemorrhage, and organ damage involving lung, liver, and kidney. Concurrent infection of DENV serotype 2 and 3 was observed. The infecting DENV-2 virus was grouped into Cosmopolitan genotype while DENV-3 virus was classified into Genotype Ⅰ. Both viruses were closely related to isolates that were endemic in Jakarta. Viremia measurement was conducted and revealed a significantly higher virus titer of DENV-3 compared to DENV-2. Conclusions: The occurrence of multi-serotype DENV infections was presented in a patient with severe clinical manifestation in Indonesia. The hyperendemicity of dengue in Indonesia may contribute to the DENV concurrent infections cases and may underlie the severity of the disease.展开更多
Dengue virus(DENV) is an arthropod-borne viral pathogen and a global health burden. Knowledge of the DENV-host interactions that mediate virus pathogenicity remains limited. Host lipid metabolism is hijacked by DENV f...Dengue virus(DENV) is an arthropod-borne viral pathogen and a global health burden. Knowledge of the DENV-host interactions that mediate virus pathogenicity remains limited. Host lipid metabolism is hijacked by DENV for virus replication in which lipid droplets(LDs) play a key role during the virus lifecycle. In this study, we reveal a novel role for phosphatase and tensin homolog deleted on chromosome 10(PTEN) in LDs-mediated DENV infection. We demonstrate that PTEN expression is downregulated upon DENV infection through post-transcriptional regulation and, in turn, PTEN overexpression enhances DENV replication. PTEN lipid phosphatase activity was found to decrease cellular LDs area and number through Akt/FoxO1/Maf1 signaling, which, together with autophagy, enhanced DENV replication and virus production. We therefore provide mechanistic insight into the interaction between lipid metabolism and the DENV replication cycle.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82130101)the Youth Innovation Promotion Association of CAS(Grant No.2021333).
文摘Dengue viruses(DENV)have spread throughout the world and pose a huge threat to human life.The most widespread serotype is type 2 DENV(DENV 2),which has no specific treatment.NS2B-NS3 protease plays a pivotal role in DENV replication because of its function in cleavage of the viral polyprotein;thus,it is considered a promising target for antiviral discovery.In this study,we developed a high-throughput screening system based on the NS2B-NS3 protease to identify candidates from an FDA-approved drug library.Eltrombopag was screened out of 3273 drugs,and demonstrated inhibition on DENV 2 at the micromolar level in vitro,significantly reducing viral loads in the targeted organs of challenged mice following intraperitoneal injection.Further mechanistic analysis showed that eltrombopag allosterically binds to the DENV 2 NS2B-NS3 protease in a reversible,noncompetitive manner,therefore inhibiting DENV 2 at the post-infection stage.In addition,eltrombopag inhibited the NS2B-NS3 proteases of DENV 4 and Zika virus,suggesting its potential as a broadspectrum antiviral agent.This study repurposed eltrombopag as a promising antiviral agent against DENV,providing an alternative for antiviral development against flaviviruses.
基金supported by the National Natural Science Foundation of China(No.82471389,No.32470986,No.82271385)Natural Science Foundation of Guangdong Province(No.2024A1515010471).
文摘Mosquito-borne flaviviruses,such as Zika virus(ZIKV)and dengue virus(DENV),cause diverse severe clinical manifestations including fever,rash,hepatitis,arthralgia,and congenital anomalies.Here,we identified a host factor,the adaptor protein complex 1 gamma 1 subunit(AP1G1),which plays an important role in both ZIKV and dengue virus 2(DENV2)infections.We explored the role of AP1G1 in ZIKV and DENV2 infections using CRISPR/Cas9 gene editing technology and RNA interference(RNAi)techniques.Knockout or silencing of AP1G1 decreases the replication of ZIKV and DENV2 in multiple human cell lines.Intriguingly,depletion of AP1G1 results in a significant reduction in ZIKV at an early stage,but decreases DENV2 replication levels during the late stage,suggesting that AP1G1 plays distinct roles in the infection by ZIKV and DENV2.Furthermore,we determined that AP1G1 mediates ZIKV-endosomal membrane fusion through inhibitor experiments and fluorescence labeling assays.Mechanistically,we found that AP1G1 exerts its pro-viral effect through binding to the ZIKV envelope glycoprotein(E protein).This interaction promotes the fusion of viral and endosomal membranes,during which the ZIKV genomic RNAs are released from the endosome into the cytoplasm,a process that facilitates viral replication.However,for DENV2 infection,AP1G1 primarily affects its viral RNA replication stage,rather than the fusion of virus-endosomal membrane.Taken together,our work demonstrates that AP1G1 plays a pro-viral role in both ZIKV and DENV2 infections via distinct mechanisms,highlighting its potential as a therapeutic target for antiviral strategies.
基金the“Metropolitan Mosquitoes Project”funded by the Swedish Research Council for Environment,Agricultural Sciences and Spatial Planning(Formas,grant number 2016-00364).
文摘Dengue virus(DENV)is a positive-sense single-stranded RNA virus belonging to the genus Flavivirus within the Flaviviridae family.Four serotypes,DENV 1-4,are distributed globally[1].Hanoi metropolitan city is an endemic hotspot for DENV transmission in Vietnam[2,3].The largest outbreak occurred in 2017,with more than 36000 cases and 7 deaths reported,causing by all four serotypes with the predominance of DENV1,following by DENV2[4,5].During the following dengue season,we collected 390 blood and serum samples from 197 hospitalized patients in a national hospital in Hanoi city,Northern Vietnam to identify the circulating DENV serotypes responsible for the 2018-2019 outbreak.
文摘The causative agent for dengue is dengue virus(DENV),with humans and mosquitoes serving as vectors.The DENV(family=Flaviviridae)is a positive-stranded RNA virus with four serotypes,DENV-1,DENV-2,DENV-3,and DENV-4.As of 2023,the disease had been reported in 80 countries with over 6.5 million cases and 7300 mortalities since then.Despite the concerning incidence and prevalence of this disease,less attention is given to the development of therapeutic remedies and preventive alternatives.The search for new antiviral bioactive compounds is therefore important and urgent.Marine organisms have been a source of diverse bioactive natural products.The large marine biodiversity and the structural diversity of their specialized metabolites provide an explorative opportunity for the discovery of novel antiviral specialized metabolites.Reported marine natural products with anti-DENV activities include fucoidan,scequinadoline A,indole derivatives,and others.Nevertheless,marine organisms are still largely underexplored as sources of antiviral drugs.With advances in metabolomics and computational screening,we may discover additional marine natural products to help with dengue treatment.
基金funded by National Natural Science Foundation of China(92578123)Shenzhen High-level Hospital Construction Fund(23250G1001)+3 种基金the Sanming Project of Medicine in Shenzhen(SZSM202311033)National Key Research and Development Program of China(2023YFC2606004)National Natural Science Foundation of China(32501262)Beijing Institute of Technology Research Fund Program for Young Scholars(6120220072).
文摘Dengue virus(DENV)is a mosquito-borne pathogen responsible for a spectrum of illnesses,including dengue fever,dengue hemorrhagic fever,and dengue shock syndrome.Nearly half of the global population is at risk of DENV infection,making it a pressing public health issue worldwide.The limited cross-protection among the four DENV serotypes(DENV1-4)and the phenomenon of antibody-dependent enhancement(ADE)have posed significant challenges to the development of effective dengue vaccines.Furthermore,there are currently no specific antiviral treatments available.This review provides an overview of DENV's key characteristics,clinical manifestations,and recent advancements in antiviral drug development-including the repurposing of approved drugs,peptidebased antiviral agents,therapeutic antibodies,natural products with antiviral potential,and host factor inhibitors-aiming to offer critical insights to inform strategies for managing and preventing dengue outbreaks.
文摘The current recommendation to avoid non-steroidal anti-inflammatory drugs(NSAIDs)in the management of dengue virus disease(DVD)is scientifically considered of very low to low certainty,despite being widely adopted worldwide.The same recommendation,initially made during the coronavirus disease 2019(COVID-19)pandemic,was subsequently proven incorrect.In this clinical report,we present evidence,for the first time globally,from a real-life practice that NSAIDs may actually be lifesaving in the early management of DVD as they have proved to be in COVID-19.Moreover,we propose that the personalized immunemodulatory Kelleni’s protocol,which includes nitazoxanide as a key component,can be safely and effectively used to manage various separate or concomitant viral infections and co-infections,including DVD.Importantly,this article contributes to the current medical knowledge in the global pursuit of a safe and effective broad-spectrum antiviral protocol that can be used to early manage multiple highly infectious viruses.However,it’s crucial that sufficiently powered controlled randomized clinical trials be conducted to thoroughly assess and evaluate the safety of NSAIDs in the early management of DVD as well as the efficacy of nitazoxanide with or without NSAIDs in its management.
文摘Background and Objectives: Dengue is an arbovirosis caused by the dengue virus with 04 serotypes. The aim of the study was to characterise the four serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) of the dengue virus circulating in Ouagadougou, Burkina Faso. Methods: This was a descriptive analytical study that included 2833 patients and was carried out from January 2021 to December 2022. Rapid diagnosis of dengue was performed using the “Dengue Duo (AgNS1/IgM/IgG)” kit (SD Bioline, Korea). Viral RNA was extracted using the QIAGEN RNA RNeasy Plus Mini Kit (Quiagen, Germany) and virus serotypes were identified using the DENGUE Real-TM Genotype PCR kit (Sacace biotechnologies, Italy). Platelet counts were also performed using the XN-1500 Sysmex. Results: The prevalence of acute infections (NS1Ag positive) by TDR was 5.7% (162/2833), with the peak of dengue virus infection occurring between October and November. On the other hand, the AgNS1+ samples tested by RT-PCR were 53.7% positive for dengue virus;this shows the extent of probable cross-reactions with rapid diagnostic tests and false positives. Serotype 1 accounted for 52.6%, 28.4% had serotype 3, 16.8% had serotype 2 and 2.1% had serotype 4. We found cases of co-infection with DENV-1 and DENV-2 in two patients, co-infection with DENV-1 and DENV-3 in three patients, co-infection with DENV-1 and DENV-4 in one patient, co-infection with DENV-3 and DENV-4 in one patient and co-infection with three serotypes, DENV-1, DENV-2 and DENV-3 in one patient. Conclusion: The study showed that all four serotypes of the dengue virus were circulating in Ouagadougou. Serotype 1 was predominant.
文摘Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.
基金supported by a research grant from the National University of Singapore
文摘Objective:To evaluate the in vitro activities of the ethyl acetate(EA) fraction of Houttuynia cordata(H.cordata) Thunb.(Saururaceae) and three of its constituent flavonoids(quercetin.quercitrin and rutin) against murine coronavirus and dengue virus(DENV).Methods:The antiviral activities of various concentrations of the EA fraction of H.cordata and flavonoids were assessed using virus neutralization tests against mouse hepatitis virus(MHV) and DENV type 2(DENV-2).Cinanserin hydrochloride was also tested against MHV.The EA fraction of H.cordata was tested for acute oral toxicity in C57BL/6 mice.Results:The EA fraction of H.cordata inhibited viral infectivity up to 6 d.Cinanserin hydrochloride was able to inhibit MHV for only 2 d.The 50%inhibitory concentrations(IC_(50)) of the EA fraction of H.cordata added before the viral adsorption stage were 0.98 μg/mL for MHV and 7.50 μg/mL for DENV-2with absence of cytotoxicity.The mice fed with the EA fraction up to 2 000 mg/kg did not induce any signs of acute toxicity,with normal histological features of major organs.Certain flavonoids exhibited comparatively weaker antiviral activity,notably quercetin which could inhibit both MHV and DENV-2.This was followed by quercitrin which could inhibit DENV-2but not MHV,whereas rutin did not exert any inhibitory effect on either virus.When quercetin was combined with quercitrin,enhancement of anti-DENV-2 activity and reduced cytotoxicity were observed.However,the synergistic efficacy of the flavonoid combination was still less than that of the EA fraction.Conclusions:The compounds in H.cordata contribute to the superior antiviral efficacy of the EA fraction which lacked cytotoxicity in vitro and acute toxicity in vim.H.cordata has much potential for the development of antiviral agents against coronavirus and dengue infections.
基金supported by the National Natural Science Foundation of China (81371794)Guangdong Natural Science Foundation (2014A030311007)
文摘Dengue virus(DENV) belongs to the genus Flavivirus of the family Flaviviridae and it is primarily transmitted via Aedes aegypti and Aedes albopictus mosquitoes. The life cycle of DENV includes attachment, endocytosis, protein translation, RNA synthesis, assembly, egress, and maturation.Recent researches have indicated that a variety of host factors, including cellular proteins and micro RNAs, positively or negatively regulate the DENV replication process. This review summarizes the latest findings(from 2014 to 2016) in the identification of the host factors involved in the DENV life cycle and Dengue infection.
基金Supported by Higher Education Commission (HEC) with Grant#PM-IPFP/HRD/HEC/2012/2770
文摘Dengue virus infection has become a global threat affecting around 100 countries in the world.Currently,there is no licensed antiviral agent available against dengue.Thus,there is a strong need to develop therapeutic strategies that can tackle this life threatening disease.RNA interference is an important and effective gene silencing process which degrades targeted RNA by a sequence specific process.Several studies have been conducted during the last decade to evaluate the efficiency of siRNA in inhibiting dengue virus replication.This review summarizes siRNAs as a therapeutic approach against dengue virus serotypes and concludes that siRNAs against virus and host genes can be next generation treatment of dengue virus infection.
基金supported by the National Natural Science Foundation of China (31870827 to X.Zhao, 31670161 to X.Zhou., and 81873964 to Y.Q.)the Hubei Natural Science Foundation (2018CFB603 to X.Zhao)the Fundamental Research Funds for the Central Universities (2042018kf0247 to X.Zhao)
文摘Dengue virus(DENV)infection is a worldwide public health threat.To date,the knowledge about the pathogenesis and progression of DENV infection is still limited.Combining global profiling based on proteomic analysis together with functional verification analysis is a powerful strategy to investigate the interplay between the virus and host cells.In the present study,quantitative proteomics has been applied to evaluate host responses(as indicated by altered proteins and modifications)in human cells(using K562 cell line)upon DENV-2 infection,as DENV-2 spreads most widely among all DENV serotypes.Comparative analysis was performed to define differentially expressed proteins in the infected cells compared to the mock-control,and it revealed critical pathogen-induced changes covering a broad spectrum of host cellular compartments and processes.We also discovered more dramatic changes(>20%,160 regulated phosphoproteins)in protein phosphorylation compared to protein expression(14%,321 regulated proteins).Most of these proteins/phosphoproteins were involved in transcription regulation,RNA splicing and processing,immune system,cellular response to stimulus,and macromolecule biosynthesis.Western blot analysis was also performed to confirm the proteomic data.Potential roles of these altered proteins were discussed.The present study provides valuable large-scale protein-related information for elucidating the functional emphasis of host cell proteins and their post-translational modifications in virus infection,and also provides insight and protein evidence for understanding the general pathogenesis and pathology of DENV.
基金This project was supported by the Provincial Science and Technology Projects of Guangdong Province,China(Grant numbers:2014A020219007,2015A020218003,2016A020219006 and 2017A020215101)the Medical Scientific Research Foundation of Guangdong Province,China(Grant numbers:A2018167).
文摘The Pearl River Delta,where Aedes albopictus(Ae.albopictus)is the only vector for dengue transmission,has exhibited one of the highest dengue burdens in southern China in recent decades.However,whether dengue virus(DENV)can overwinter in Ae.albopictus in the Pearl River Delta has not been determined to date.In this study,300 field-derived Ae.albopictus mosquitoes from Guangzhou that were infected with the predominant endemic DENV-1 strain were investigated under simulated urban balcony environment from October 16,2016,to June 16,2017.The vertical transmission of DENV in the infected overwintering Ae.albopictus was analyzed.The DENV infected overwintering mosquitoes were evaluated for viral load at nine-time points using reverse transcription-quantitative PCR.The vector competence of the infected overwintering Ae.albopictus was also investigated by using suckling mice.Adult mosquitoes and larvae were found during the observation period.The vertical transmission of DENV-1 was documented.The DENV-1-positive rates between overwintering males and females had no difference.The proportion of DENV-1-positive overwintering mosquitoes decreased over time and had no difference beyond three months after the experiment.Overwintering mosquitoes can spread DENV-1 to hosts.No engorged mosquitoes at an ambient temperature below 15℃were observed.The ratio of engorged mosquitoes was positively correlated with the ambient temperature ranging from 15 to 30℃.Our results demonstrated that DENV can overwinter in Ae.albopictus in the Pearl River Delta,Ae.albopictus is the competent vector for DENV,and maintain autochthonous dengue outbreaks in the Pearl River Delta through vertical transmission.
基金supported by the Center of Excellence in Clinical Virology.Chulalongkorn University,CU Centenary Academic Development ProjectKing Chulalongkorn Memorial Hospital,the National Research University Project of CHEthe Ratchadaphiseksonphot Endowment Fund(HR1155A)
文摘Objective:To develop diagnostic test for detection chikungunya virus(CHIKV and Dengue virus (DENV) infection.Methods:We have performed a rapid,accurate laboratory confirmative method to simultaneously detect,quantify and differentiate CHIKV and DENV infection by single-step multiplex real-time RT-PCR.Results:The assay’s sensitivity was 97.65%,specificity was 92.59% and accuracy was 95.82%when compared to conventional RT-PCR.Additionally,there was no cross-reaction between CHIKV,DENV,Japanese encephalitis virus,hepatitis C,hepatitis A or hepatitis E virus.Conclusions:This rapid and reliable assay provides a means for simultaneous early diagnosis of CHIKV and DENV in a single-step reaction.
基金the Universiti Tunku Abdul Rahman,Malaysia,in providing funding to this project through UTARSRF strategic research funding scheme IPRS/RMC/UTARSRF/PROGRAMME 2014-C1/007。
文摘Dengue virus(DENV) has emerged as a major virus that is spread by mosquitoes. Recently, it has spread to more than a hundred nations but continues to lack specific treatable medication. Many traditional Chinese medicinal(TCM) plants are in practice for dengue fever in dengue endemic regions. These traditional medicines persevere with treatments, which modern medicines lack. The study aims to substantiate the anti-dengue potential of some traditional herbs and make them available for further studies to facilitate TCM users. Twelve TCM plants aqueous extracts were evaluated, which are described as cool herbs used for the diseases with high fever. Lead plants were established through detailed in vitro foci forming unit reduction analysis(FFURA) against all four serotypes and validated through quantitative real-time RT-PCR(q RT-PCR). Four plants potentially inhibited the virus in primary phenotypic in vitro evaluation. Two lead plants Dryopteris crassirhizoma(DC) and Morus alba(MA) were identified with half minimal inhibitory concentration(IC50) 130 and 221 μg m L^-1, respectively, while the selectivity indices(SI) were 4.21 and 4.62, respectively. Lead plants equally inhibited all four serotypes of DENV. Time-of-addition analysis suggested that, DC was active at later stages of viral replication, whereas MA was active during the early stages and even showed some prophylactic activity. Liquid chromatography-mass spectrometry(HPLC/MS) analysis revealed presence of flavonoids. DC and MA are identified as potential anti-dengue plants, active against varied stages of dengue virus replication cycle. These results may serve as the base knowledge for further investigation on their combined treatments or integrative treatment with western medicines, which may improve the overall anti-dengue activity in future.
基金support of the National University of SingaporeQuaid-i-Azam University
文摘Objective: To investigate the inhibitory effects against dengue virus serotype 2(DENV-2) by five different fractions(extracted by methanol, ethanol, benzene, chloroform and n-hexane) of Rumex dentatus, Commelina benghalensis, Ajuga bracteosa and Ziziphus mauritiana, as well as their constituents(gallic acid, emodin, and isovanillic acid). Methods: All the samples were tested for cytotoxicity on baby hamster kidney cells by MTT assay and for anti-DENV-2 activity by plaque reduction neutralization assay using two DENV-2 doses(45 and 90 plaqueforming units or PFU). Results: All the samples except isovanillic acid exhibited significant prophylactic effects against DENV-2 infectivity(without cytotoxicity) when administered to cells before infection, but were not effective when given 6 h post-infection. The methanol extract of Rumex dentatus demonstrated the highest antiviral efficacy by inhibiting DENV-2 replication, with IC_(50) of 0.154 μg/mL and 0.234 μg/mL, when added before infection with 45 and 90 PFU of virus, respectively. Gallic acid also exhibited significant antiviral effects by prophylactic treatment prior to virus adsorption on cells, with IC_(50) of 0.191 μg/mL and 0.522 μg/mL at 45 and 90 PFU of DENV-2 infection, respectively. Conclusions: The highly potent activities of the extracts and constituent compounds of these plants against DENV-2 infectivity highlight their potential as targets for further research to identify novel antiviral agents against dengue.
基金supported by the National Natural Science Foundation of China (81772172, 81471957, 81671971, U1602223)
文摘Dengue fever, caused by dengue viruses(DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate(pV-D4 ME) expressing prM-E protein of DENV serotype 4(DENV-4) was constructed, and its immunogenicity and protection were evaluated in immunocompetent BALB/c mice. The pV-D4 ME candidate vaccine induced effective humoral and cellular immunity of mice against DENV-4 in vivo when administered both at 50 μg and 5 μg through electroporation. Two weeks after receiving three immunizations, both doses of pV-D4 ME DNA were shown to confer effective protection against lethal DENV-4 challenge. Notably, at 6 months after the three immunizations, 50 μg, but not 5 μg, of pV-D4 ME could provide stable protection(100% survival rate) against DENV-4 lethal challenge without any obvious clinical signs. These results suggest that immunization with 50 μg pV-D4 ME through electroporation could confer effective and long-term protection against DENV-4, offering a promising approach for development of a novel DNA vaccine against DENVs.
基金National Key Research and Development Plan of China,Grant/Award Number:2018YFA0507202,2020YFC1200100 and 2021YFC2300200National Natural Science Foundation of China,Grant/Award Number:31825001,32188101,81730063,81961160737 and 82102389+5 种基金Provincial Innovation Team for the Prevention and Control of Highly Pathogenic Pathogens,Institute of Medical Biology,Chinese Academy of Medical Sciences,Grant/Award Number:202105AE160020Shenzhen San-Ming Project for Prevention and Research on Vector-borne Diseases,Grant/Award Number:SZSM201611064Shenzhen Science and Technology Project,Grant/Award Number:JSGG20191129144225464Tsinghua University Spring Breeze Fund,Grant/Award Number:2020Z99CFG017Young Elite Scientists Sponsorship Program,Grant/Award Number:2021QNRC001Yunnan Cheng Gong Expert Work-Station,Grant/Award Number:202005AF150034。
文摘Dengue virus(DENV)is one of the most important arboviral pathogens in the tropics and subtropics,and nearly one-third of the world's population is at risk of infection.The transmission of DENV involves a sylvatic cycle between nonhuman primates(NHP)and Aedes genus mosquitoes,and an endemic cycle between human hosts and predominantly Aedes aegypti.DENV belongs to the genus Flavivirus of the family Flaviviridae and consists of four antigenically distinct serotypes(DENV-1-4).Phylogenetic analyses of DENV have revealed its origin,epidemiology,and the drivers that determine its molecular evolution in nature.This review discusses how phyloge-netic research has improved our understanding of DENV evolution and how it affects viral ecology and improved our ability to analyze and predict future DENV emergence.
文摘Objective: To describe the clinical manifestation of patient with severe dengue, to identify the serotypes and genotypes of dengue viruses(DENV) which concurrently infecting the patient, and to explore the possible relationship of severe dengue with the concurrent infection of DENV. Methods: Dengue diagnosis was performed using NS1 antigen detection and Ig G/Ig M ELISA. Standard clinical and laboratory examinations were performed to obtain the clinical and hematological data. DENV concurrent infections were detected and confirmed using RT-PCR and DENV Envelope gene sequencing. Phylogenetic analyses were performed to determine the genotypes of the viruses. Results: The patient was classified as having severe dengue characterized by severe plasma leakage, hemorrhage, and organ damage involving lung, liver, and kidney. Concurrent infection of DENV serotype 2 and 3 was observed. The infecting DENV-2 virus was grouped into Cosmopolitan genotype while DENV-3 virus was classified into Genotype Ⅰ. Both viruses were closely related to isolates that were endemic in Jakarta. Viremia measurement was conducted and revealed a significantly higher virus titer of DENV-3 compared to DENV-2. Conclusions: The occurrence of multi-serotype DENV infections was presented in a patient with severe clinical manifestation in Indonesia. The hyperendemicity of dengue in Indonesia may contribute to the DENV concurrent infections cases and may underlie the severity of the disease.
基金funded by the National Natural Science Foundation of China (81171564)the National Key Research and Development Program of China (2016YFC1200400)the National S&T Major Project for Infectious Diseases Control (2017ZX10304403)。
文摘Dengue virus(DENV) is an arthropod-borne viral pathogen and a global health burden. Knowledge of the DENV-host interactions that mediate virus pathogenicity remains limited. Host lipid metabolism is hijacked by DENV for virus replication in which lipid droplets(LDs) play a key role during the virus lifecycle. In this study, we reveal a novel role for phosphatase and tensin homolog deleted on chromosome 10(PTEN) in LDs-mediated DENV infection. We demonstrate that PTEN expression is downregulated upon DENV infection through post-transcriptional regulation and, in turn, PTEN overexpression enhances DENV replication. PTEN lipid phosphatase activity was found to decrease cellular LDs area and number through Akt/FoxO1/Maf1 signaling, which, together with autophagy, enhanced DENV replication and virus production. We therefore provide mechanistic insight into the interaction between lipid metabolism and the DENV replication cycle.
