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1.
Acta Pharmacol Sin ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987389

RESUMO

Influenza A virus (IAV) is a widespread pathogen that poses a significant threat to human health, causing pandemics with high mortality and pathogenicity. Given the emergence of increasingly drug-resistant strains of IAV, currently available antiviral drugs have been reported to be inadequate to meet clinical demands. Therefore, continuous exploration of safe, effective and broad-spectrum antiviral medications is urgently required. Here, we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo. Moreover, J1 exhibits broad-spectrum antiviral activity against enveloped viruses, including IAV, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (HCoV-OC43), herpes simplex virus type 1 (HSV-1) and HSV-2. In this study, we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro. The results showed that J1 inhibited infection by IAV strains, including H1N1, H7N9, H5N1 and H3N2, as well as by oseltamivir-resistant strains. Mechanistic studies have shown that J1 blocks IAV infection mainly through specific interactions with the influenza virus hemagglutinin HA2 subunit, thereby blocking membrane fusion. BALB/c mice were used to establish a model of acute lung injury (ALI) induced by IAV. Treatment with J1 increased survival rates and reduced viral titers, lung index and lung inflammatory damage in virus-infected mice. In conclusion, J1 possesses significant anti-IAV effects in vitro and in vivo, providing insights into the development of broad-spectrum antivirals against future pandemics.

2.
Nucleic Acids Res ; 50(D1): D83-D92, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34530446

RESUMO

Many circRNA transcriptome data were deposited in public resources, but these data show great heterogeneity. Researchers without bioinformatics skills have difficulty in investigating these invaluable data or their own data. Here, we specifically designed circMine (http://hpcc.siat.ac.cn/circmine and http://www.biomedical-web.com/circmine/) that provides 1 821 448 entries formed by 136 871 circRNAs, 87 diseases and 120 circRNA transcriptome datasets of 1107 samples across 31 human body sites. circMine further provides 13 online analytical functions to comprehensively investigate these datasets to evaluate the clinical and biological significance of circRNA. To improve the data applicability, each dataset was standardized and annotated with relevant clinical information. All of the 13 analytic functions allow users to group samples based on their clinical data and assign different parameters for different analyses, and enable them to perform these analyses using their own circRNA transcriptomes. Moreover, three additional tools were developed in circMine to systematically discover the circRNA-miRNA interaction and circRNA translatability. For example, we systematically discovered five potential translatable circRNAs associated with prostate cancer progression using circMine. In summary, circMine provides user-friendly web interfaces to browse, search, analyze and download data freely, and submit new data for further integration, and it can be an important resource to discover significant circRNA in different diseases.


Assuntos
Biologia Computacional , Bases de Dados Genéticas , RNA Circular/genética , Transcriptoma/genética , Doenças Genéticas Inatas/genética , Humanos , Neoplasias/genética , RNA Circular/classificação
3.
Emerg Infect Dis ; 29(6): 1254-1257, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37209692

RESUMO

We isolated a new orthonairovirus from Dermacentor silvarum ticks near the China-North Korea border. Phylogenetic analysis showed 71.9%-73.0% nucleic acid identity to the recently discovered Songling orthonairovirus, which causes febrile illness in humans. We recommend enhanced surveillance for infection by this new virus among humans and livestock.


Assuntos
Dermacentor , Vírus , Humanos , Animais , República Democrática Popular da Coreia/epidemiologia , Filogenia , China/epidemiologia
4.
J Virol ; 96(4): e0146421, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-34586860

RESUMO

Bats are reservoirs of important zoonotic viruses like Nipah and SARS viruses. However, whether the blood-sucking arthropods on the body surface of bats also carry these viruses and the relationship between viruses carried by the blood-sucking arthropods and viruses carried by bats have not been reported. This study collected 686 blood-sucking arthropods on the body surface of bats from Yunnan Province, China, between 2012 and 2015, and they included wingless bat flies, bat flies, ticks, mites, and fleas. The viruses carried by these arthropods were analyzed using a meta-transcriptomic approach, and 144 highly diverse positive-sense single-stranded RNA, negative-sense single-stranded RNA, and double-stranded RNA viruses were found, of which 138 were potentially new viruses. These viruses were classified into 14 different virus families or orders, including Bunyavirales, Mononegavirales, Reoviridae, and Picornavirales. Further analyses found that Bunyavirales were the most abundant virus group (84% of total virus RNA) in ticks, whereas narnaviruses were the most abundant (52 to 92%) in the bat flies and wingless bat flies libraries, followed by solemoviruses (1 to 29%) and reoviruses (0 to 43%). These viruses were highly structured based on the arthropod types. It is worth noting that no bat-borne zoonotic viruses were found in the virome of bat-infesting arthropod, seemingly not supporting that bat surface arthropods are vectors of zoonotic viruses carried by bats. IMPORTANCE Bats are reservoirs of many important viral pathogens. To evaluate whether bat-parasitic blood-sucking arthropods participate in the circulation of these important viruses, it is necessary to conduct unbiased virome studies on these arthropods. We evaluated five types of blood-sucking parasitic arthropods on the surface of bats in Yunnan, China, and identified a variety of viruses, some of which had high prevalence and abundance levels, although there is limited overlap in virome between distant arthropods. While most of the virome discovered here is potentially arthropod-specific viruses, we identified three possible arboviruses, including one orthobunyavirus and two vesiculoviruses (family Rhabdoviridae), suggesting bat-parasitic arthropods carry viruses with risk of spillage, which warrants further study.


Assuntos
Artrópodes/virologia , Quirópteros/parasitologia , Reservatórios de Doenças/virologia , Viroma , Animais , Arbovírus/classificação , Arbovírus/genética , Arbovírus/isolamento & purificação , Artrópodes/classificação , Artrópodes/genética , China , Reservatórios de Doenças/parasitologia , Ectoparasitoses/parasitologia , Ectoparasitoses/veterinária , Ectoparasitoses/virologia , Filogenia , Vírus de RNA/classificação , Vírus de RNA/genética , Vírus de RNA/isolamento & purificação , Viroma/genética
5.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(1): 47-53, 2023 Jan 30.
Artigo em Zh | MEDLINE | ID: mdl-36752006

RESUMO

OBJECTIVE: Current mainstream PET scattering correction methods are introduced and evaluated horizontally, and finally, the existing problems and development direction of scattering correction are discussed. METHODS: Based on NeuWise Pro PET/CT products of Neusoft Medical System Co. Ltd. , the simulation experiment is carried out to evaluate the influence of radionuclide distribution out of FOV (field of view) on the scattering estimation accuracy of each method. RESULTS: The scattering events produced by radionuclide out of FOV have an obvious impact on the spatial distribution of scattering, which should be considered in the model. The scattering estimation accuracy of Monte Carlo method is higher than single scatter simulation (SSS). CONCLUSIONS: Clinically, if the activity of the adjacent parts out of the FOV is high, such as brain, liver, kidney and bladder, it is likely to lead to the deviation of scattering estimation. Considering the Monte Carlo scattering estimation of the distribution of radionuclide out of FOV, it's helpful to improve the accuracy of scattering distribution estimation.


Assuntos
Encéfalo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Espalhamento de Radiação , Simulação por Computador , Método de Monte Carlo , Imagens de Fantasmas , Processamento de Imagem Assistida por Computador
6.
Emerg Infect Dis ; 26(10): 2435-2438, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32946723

RESUMO

We isolated 17 viral strains capable of causing cytopathic effects in mammalian cells and death in neonatal mice from sand flies in China. Phylogenetic analysis showed that these strains belonged to the genus Phlebovirus. These findings highlight the need to control this potentially emerging virus to help safeguard public health.


Assuntos
Phlebovirus , Psychodidae , Animais , China/epidemiologia , Camundongos , Phlebovirus/genética , Filogenia
7.
Virol J ; 17(1): 105, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32664965

RESUMO

BACKGROUND: Liao ning virus (LNV) is a member of the genus Seadornavirus, family Reoviridae and has been isolated from kinds of vectors in Asia and Australia. However, there are no systematic studies describe the molecular genetic evolution and migration of LNVs. With the development of bioinformatics, viral genetic data combining the information of virus isolation time and locations could be integrated to infer the virus evolution and spread in nature. METHODS: Here, a phylogenetic and phylogeographic analysis using Bayesian Markov chain Monte Carlo simulations was conducted on the LNVs isolated from a variety of vectors during 1990-2014 to identify the evolution and migration patterns of LNVs. RESULTS: The results demonstrated that the LNV could be divided into 3 genotypes, of which genotype 1 mainly composed of LNVs isolated from Australia during 1990 to 2014 and the original LNV strain (LNV-NE97-31) isolated from Liaoning province in northern China in 1997, genotype 2 comprised of the isolates all from Xinjiang province in western China and genotype 3 consisted the isolates from Qinghai and Shanxi province of central China. LNVs emerged about 272 years ago and gradually evolved into three lineages in the order genotype 1, genotype 2 and genotype 3. Following phylogeographic analysis, it shows genotype 1 LNVs transmitted from Australia (113°E-153°E,10°S-42°S) to Liaoning province (118°E-125°E,38°N-43°N) in Northeast Asian continent then further spread across the central part of China to western China (75°E-95°E,35°N-50°N). CONCLUSION: LNVs were initially isolated from Liaoning province of China in the Northeast Asia, however, the present study revealed that LNVs were first appeared in Australia in the South Pacific region and transmitted to mainland China then rapidly spread across China and evolved three different genotypes. The above results suggested that LNV had the characteristics of long-distance transmission and there were great genetic diversity existed in the LNV population. Notably, current information of 80 strains of LNVs are limited. It is of great importance to strengthen the surveillance of LNVs to explore its real origin in nature and monitoring of the LNVs' population variation and maintain vigilance to avoid LNV breaking through the species barrier and further clarify its relationship to human and animal infection.


Assuntos
Evolução Molecular , Genótipo , Filogenia , Reoviridae/genética , Animais , Austrália , Teorema de Bayes , China , Culicidae/classificação , Culicidae/virologia , Filogeografia , Reoviridae/classificação , Análise de Sequência de DNA
8.
Arch Microbiol ; 202(4): 807-813, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31844947

RESUMO

Totiviridae, a viral family of double-stranded RNA (dsRNA) viruses, contain a single dsRNA genome 4.6-7.0 kb in length. Totiviridae were initially only known to infect fungi and other eukaryotes as well as plants, but an increase in totiviruses has been detected in insects, mosquitoes, and bats. Here, we describe the isolation and characterization of a strain belonging to the family Totiviridae isolated from Culex tritaeniorhynchus in Kenli, China, in 2016. We isolated a totivirus from field-collected mosquitoes in China by cell culture in Aedes albopictus C6/36 cells, identified the virus by morphological observation and complete genome sequencing, and characterized it by phylogenetic analysis. Transmission electron microscopy identified icosahedral, non-enveloped virus particles with a mean diameter of 35-40 nm. The genome was 7612 bp in length, including two open reading frames (ORFs). ORF1 (5058 nt) encodes the capsid protein, while ORF2 (2216 nt) encodes the viral RNA-dependent RNA polymerase (RdRp). Nucleotide and amino acid homology analysis of isolate showed higher levels of sequence identity with isolate CTV_NJ2 (China, 2010) with 94.87% nucleic acid identity and 97.32% amino acid identity. The isolate was designated C. tritaeniorhynchus totivirus KL (CTV-KL). This is the first identification of a totivirus in a C. tritaeniorhynchus in northern China. Analysis of the virus's morphology, characteristic and genome organization will further enrich our understanding of the molecular and biological characteristics of dsRNA Totiviridae viruses.


Assuntos
Culex/virologia , Totivirus/genética , Aedes/citologia , Aedes/virologia , Animais , Proteínas do Capsídeo/genética , Linhagem Celular , China , Genoma Viral/genética , Microscopia Eletrônica de Transmissão , Fases de Leitura Aberta/genética , Filogenia , RNA Polimerase Dependente de RNA , Totivirus/classificação , Totivirus/isolamento & purificação , Totivirus/ultraestrutura
9.
Virol J ; 16(1): 8, 2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30634973

RESUMO

BACKGROUND: Yokose virus was first isolated from bats (Miniopterus fuliginosus) collected in Yokosuka, Japan, in 1971, and is a new member of the family Flaviviridae, genus Flavivirus. In this study, we isolated a Yokose virus from a serum sample of Myotis daubentonii (order Chiroptera, family Vespertilionidae) collected in Yunnan province, China in 2013. METHODS: The serum specimens of bat were used to inoculate in BHK-21 and Vero E6 cells for virus isolation. Then the viral complete genome sequence was obtained and was used for phylogenetic analysis performed by BEAST software package. RESULTS: The virus was shown to have cytopathic effects in mammalian cells (BHK-21 and Vero E6). Genome sequencing indicated that it has a single open reading frame (ORF), with a genome of 10,785 nucleotides in total. Phylogenetic analysis of the viral genome suggests that XYBX1332 is a Yokose virus (YOKV) of the genus Flavivirus. Nucleotide and amino acid homology levels of the ORF of XYBX1332 and Oita-36, the original strain of YOKV, were 72 and 82%, respectively. The ORFs of XYBX1332 and Oita-36 encode 3422 and 3425 amino acids, respectively. In addition, the non-coding regions (5'- and 3'-untranslated regions [UTRs]) of these two strains differ in length and the homology of the 5'- and 3'-UTRs was 81.5 and 78.3%, respectively. CONCLUSION: The isolation of YOKV (XYBX1332) from inland China thousands of kilometers from Yokosuka, Japan, suggests that the geographical distribution of YOKV is not limited to the islands of Japan and that it can also exist in the inland areas of Asia. However, there are large differences between the Chinese and Japanese YOKV strains in viral genome.


Assuntos
Quirópteros/virologia , Flavivirus/genética , Variação Genética , Genoma Viral , Animais , China , Chlorocebus aethiops , Flavivirus/isolamento & purificação , Infecções por Flavivirus/veterinária , Fases de Leitura Aberta , Filogenia , RNA Viral/genética , Células Vero , Sequenciamento Completo do Genoma
10.
Rev Med Virol ; 28(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29210509

RESUMO

Since the 1980s, a comprehensive field and laboratory investigation has been conducted throughout China, and a total of 29 virus species belonging to 7 families and 13 genera were identified through virological, morphological, and immunological methods, as well as whole-genome sequencing and molecular genetic analyses. Most of the virus isolates belong to 9 genera in the families Flaviviridae, Bunyaviridae, Togaviridae, and Reoviridae. Among them, 4 genera (Orthobunyavirus, Bunyavirus, Phlebovirus, and Nairovirus) belong to the family Bunyaviridae and 3 genera (Seadonavirus, Orbivirus, and Cypovirus) belong to the family Reoviridae. Analyses of the relationships between viruses and human/animal diseases indicated that Japanese encephalitis virus, dengue virus, severe fever with thrombocytopenia syndrome virus, tick-borne encephalitis virus, Crimean-Congo hemorrhagic fever virus, West Nile virus, and Tahyna virus can cause human and animal infections and disease epidemics in China. This review systematically introduces the current status of the diversity and geographical distribution of arboviruses and vectors in China. In addition, our results provide strong technical support for the prevention and control of arboviral diseases, the treatment of epidemics, and the early warning and prediction of diseases, and so they are significant for the control and prevention of arboviral diseases in Asia and around the world.


Assuntos
Infecções por Arbovirus/epidemiologia , Infecções por Arbovirus/virologia , Arbovírus , Animais , Infecções por Arbovirus/diagnóstico , Infecções por Arbovirus/transmissão , Arbovírus/classificação , Arbovírus/genética , Arbovírus/isolamento & purificação , China/epidemiologia , Vetores de Doenças , Geografia Médica , Humanos , Incidência , Filogenia
11.
J Immunol ; 199(4): 1476-1489, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28687661

RESUMO

In this study, we used a systems vaccinology approach to identify temporal changes in immune response signatures to the yellow fever (YF)-17D vaccine, with the aim of comprehensively characterizing immune responses associated with protective immunity. We conducted a cohort study in which 21 healthy subjects in China were administered one dose of the YF-17D vaccine; PBMCs were collected at 0 h and then at 4 h and days 1, 2, 3, 5, 7, 14, 28, 84, and 168 postvaccination, and analyzed by transcriptional profiling and immunological assays. At 4 h postvaccination, genes associated with innate cell differentiation and cytokine pathways were dramatically downregulated, whereas receptor genes were upregulated, compared with their baseline levels at 0 h. Immune response pathways were primarily upregulated on days 5 and 7, accompanied by the upregulation of the transcriptional factors JUP, STAT1, and EIF2AK2. We also observed robust activation of innate immunity within 2 d postvaccination and a durable adaptive response, as assessed by transcriptional profiling. Coexpression network analysis indicated that lysosome activity and lymphocyte proliferation were associated with dendritic cell (DC) and CD4+ T cell responses; FGL2, NFAM1, CCR1, and TNFSF13B were involved in these associations. Moreover, individuals who were baseline-seropositive for Abs against another flavivirus exhibited significantly impaired DC, NK cell, and T cell function in response to YF-17D vaccination. Overall, our findings indicate that YF-17D vaccination induces a prompt innate immune response and DC activation, a robust Ag-specific T cell response, and a persistent B cell/memory B cell response.


Assuntos
Imunidade Adaptativa/genética , Perfilação da Expressão Gênica , Imunidade Inata/genética , Vacina contra Febre Amarela/imunologia , Adulto , Anticorpos Antivirais/sangue , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Estudos de Coortes , Citocinas/genética , Citocinas/imunologia , Células Dendríticas/imunologia , Desmoplaquinas/genética , Desmoplaquinas/imunologia , Feminino , Regulação da Expressão Gênica , Humanos , Memória Imunológica , Leucócitos Mononucleares/imunologia , Ativação Linfocitária , Masculino , Biologia de Sistemas/métodos , Vacinação , Febre Amarela/prevenção & controle , Vacina contra Febre Amarela/administração & dosagem , gama Catenina
12.
Angew Chem Int Ed Engl ; 58(35): 12102-12106, 2019 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-31233271

RESUMO

An unconventional organic molecule (TBBU) showing obvious long-lived room temperature phosphorescence (RTP) is reported. X-ray single crystal analysis demonstrates that TBBU molecules are packed in a unique fashion with side-by-side arranged intermolecular aromatic rings, which is entirely different from the RTP molecules reported to date. Theoretical calculations verify that the extraordinary intermolecular interaction between neighboring molecules plays an important role in RTP of TBBU crystals. More importantly, the polymer film doped with TBBU inherits its distinctive RTP property, which is highly sensitive to oxygen. The color of the doped film changes and its RTP lifetime drops abruptly through a dynamic collisional quenching mechanism with increasing oxygen fraction, enabling visual and quantitative detection of oxygen. Through analyzing the grayscale of the phosphorescence images, a facile method is developed for rapid, visual, and quantitative detection of oxygen in the air.

13.
Biochem Cell Biol ; 96(3): 332-341, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29024602

RESUMO

It has been suggested that cell migration inducing hyaluronan binding protein (CEMIP) contributes to the carcinogenesis of colorectal cancer (CRC). Cancer cells can adapt to endoplasmic reticulum (ER) stress by initiating an unfolded protein response (UPR). This study aimed to investigate whether CEMIP affects the UPR of CRC cells, with a focus on 78 kDa glucose-regulated protein (GRP78, a major ER chaperone). We found that knockdown of CEMIP inhibited cell proliferation and induced a G1 arrest in SW480 CRC cells. The levels of cyclin D1 and cyclin E1 and phospho-retinoblastoma, which are known to promote the cell cycle progression from G0 or G1 into S phase, were decreased in CEMIP-silenced cells. CEMIP shRNA induced apoptosis and inhibited GRP78 expression in SW480 and Colo205 cells. The basal UPR of cancer cells was attenuated by CEMIP shRNA, as evidenced by the decreased expression of UPR sensors, protein kinase R-like endoplasmic reticulum kinase (PERK), inositol requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6). Furthermore, CEMIP silencing sensitized CRC cells to thapsigargin-induced apoptosis. Our study demonstrates that the in-vitro anti-proliferative and pro-apoptotic effects in CRC cells that were induced by silencing CEMIP may be associated with GRP78 repression and UPR attenuation.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Proteínas de Choque Térmico/metabolismo , Proteínas/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação para Baixo , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/genética , Técnicas de Silenciamento de Genes/métodos , Proteínas de Choque Térmico/genética , Humanos , Hialuronoglucosaminidase , Proteínas/genética , Transdução de Sinais/efeitos dos fármacos , Resposta a Proteínas não Dobradas/genética
14.
Virol J ; 15(1): 64, 2018 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-29625620

RESUMO

BACKGROUND: Kadipiro virus (KDV) belongs to the Reoviridae family, which consists of segmented, non-enveloped, double-stranded RNA viruses. It has previously been isolated from Culex, Anopheles, Armigeres and Aedes mosquitoes in Indonesia and China. Here, we describe the isolation and characterization of SDKL1625 from Anopheles sinensis mosquitoes in Shandong province, China. METHODS: In this study, we isolated Kadipiro virus in Aedes albopictus C6/36 cell culture and the complete genome sequencing was made by next generation sequencing. RESULTS: We isolated and characterized a Kadipiro virus from Anopheles sinensis mosquitoes in 2016 in Shandong province, China. Nucleotide and amino acid homology analysis of SDKL1625 showed higher levels of sequence identity with QTM27331 (Odonata, China, 2016) than with JKT-7075 (Culex fuscocephalus, Indonesia, 1981). The SDKL1625 has 86-97% amino acid identity with the JKT-7075, 88-99% amino acid identity with the QTM27331. Among the 12 fragments, VP1, VP2, VP4, VP6, VP7, VP9 and VP12 showed high amino acid identity (> 90%) and VP5 showed the lowest identity (86% and 88%). CONCLUSIONS: This is the first identification of KDV from mosquito in China. Virus morphology and genome organization were also determined, which will further enrich our understanding of the molecular biological characteristics of KDV and seadornaviruses.


Assuntos
Anopheles/virologia , Coltivirus/classificação , Coltivirus/genética , Animais , Linhagem Celular , China , Coltivirus/isolamento & purificação , Coltivirus/ultraestrutura , Genoma Viral , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Insetos Vetores/virologia , Filogenia , RNA Viral
15.
PLoS Pathog ; 11(4): e1004848, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25915054

RESUMO

Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.


Assuntos
Aedes/imunologia , Encéfalo/imunologia , Vírus da Dengue/imunologia , Vírus da Encefalite Japonesa (Espécie)/imunologia , Interações Hospedeiro-Patógeno , Proteínas do Tecido Nervoso/metabolismo , Neurônios/imunologia , Aedes/efeitos dos fármacos , Aedes/virologia , Animais , Antivirais/metabolismo , Antivirais/farmacologia , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/virologia , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/fisiologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Vírus da Encefalite Japonesa (Espécie)/efeitos dos fármacos , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Feminino , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Proteínas de Insetos/antagonistas & inibidores , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/farmacologia , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/virologia , Filogenia , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Proteínas do Envelope Viral/antagonistas & inibidores , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/metabolismo , Internalização do Vírus/efeitos dos fármacos
16.
Org Biomol Chem ; 14(33): 7875-82, 2016 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-27454320

RESUMO

Lengthy peptides corresponding to the C-terminal heptad repeat (C-peptides) of human immunodeficiency virus type 1 (HIV-1) gp41 are potent inhibitors against virus-cell fusion. Designing short C-peptide-based HIV-1 fusion inhibitors could potentially redress the physicochemical and technical liabilities of a long-peptide therapeutic. However, designing such inhibitors with high potency has been challenging. We generated a conjugated architecture by incorporating small-molecule inhibitors of gp41 into the N-terminus of a panel of truncated C-peptides. Among these small molecule-capped short peptides, the 26-residue peptide Indole-T26 inhibited HIV-1 Env-mediated cell-cell fusion and viral replication at low nanomolar levels, reaching the potency of the only clinically used 36-residue peptide T20 (enfuvirtide). Collectively, our work opens up a new avenue for developing short peptide-based HIV-1 fusion inhibitors, and may have broad applicability to the development of modulators of other class I fusion proteins.


Assuntos
Fármacos Anti-HIV/farmacologia , Desenho de Fármacos , Inibidores da Fusão de HIV/farmacologia , HIV-1/efeitos dos fármacos , Peptídeos/farmacologia , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Linhagem Celular , Proteína gp41 do Envelope de HIV/química , Inibidores da Fusão de HIV/síntese química , Inibidores da Fusão de HIV/química , Humanos , Estrutura Molecular , Peptídeos/síntese química , Peptídeos/química , Replicação Viral/efeitos dos fármacos
17.
Virol J ; 12: 43, 2015 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-25884184

RESUMO

BACKGROUND: Japanese encephalitis virus (JEV) is the etiological agent of Japanese encephalitis (JE), one of the most serious viral encephalitis worldwide. Five genotypes have been classified based on phylogenetic analysis of the viral envelope gene or the complete genome. Previous studies based on four genotypes have reported that in evolutionary terms, genotype 1 JEV is the most recent lineage. However, until now, no systematic phylogenetic analysis was reported based on whole genomic sequence of all five JEV genotypes. FINDINGS: In this study, phylogenetic analysis using Bayesian Markov chain Monte Carlo simulations was conducted on the whole genomic sequences of all five genotypes of JEV. The results showed that the most recent common ancestor (TMRCA) for JEV is estimated to have occurred 3255 years ago (95% highest posterior density [HPD], -978 to-6125 years). Chronologically, this ancestral lineage diverged to produce five recognized virus genotypes in the sequence 5, 4, 3, 2 and 1. Population dynamics analysis indicated that the genetic diversity of the virus peaked during the following two periods: 1930-1960 and 1980-1990, and the population diversity of JEV remained relatively high after 2000. CONCLUSIONS: Genotype 5 is the earliest recognized JEV lineage, and the genetic diversity of JEV has remained high since 2000.


Assuntos
Vírus da Encefalite Japonesa (Espécie)/genética , Encefalite Japonesa/virologia , Evolução Molecular , Genoma Viral , Sequência de Bases , Teorema de Bayes , Vírus da Encefalite Japonesa (Espécie)/classificação , Vírus da Encefalite Japonesa (Espécie)/isolamento & purificação , Variação Genética , Genótipo , Humanos , Dados de Sequência Molecular , Filogenia
18.
Arch Virol ; 160(9): 2259-68, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26118548

RESUMO

Culex flavivirus (CxFV) is an insect-specific virus of the genus Flavivirus. CxFV strains have been isolated from Cx. pipiens, Cx. quinquefasciatus, and other Cx. species in Asia, Africa, North America, Central America and South America. CxFV was isolated for the first time in China in 2006. As this is a novel flavivirus, we explored the distribution and genetic characteristics of Culex flavivirus in China. A total of 46,649 mosquitoes were collected in seven provinces between 2004 and 2012 and were analysed in 871 pools. 29 CxFV RNAs from Cx. pipiens, Cx. tritaeniorhynchus, Anopheles Sinensis, and Culex spp. tested positive for CxFV in real-time RT-PCR. 6 CxFV strains were isolated from Cx. species collected in Shandong, Henan, and Shaanxi provinces, while no virus or viral RNA was detected in samples from Sichuan, Chongqing, Hubei, and Fujian. Phylogenetic analysis of the envelope gene indicated that Chinese strains formed a robust subgroup of genotype 1, together with viruses from the United States and Japan. This study demonstrates that the geographic distribution of CxFV in China is widespread, but geographical boundaries to spread are apparent. Our findings suggest that CxFV can infect various mosquito species in nature.


Assuntos
Anopheles/virologia , Culex/virologia , Flavivirus/isolamento & purificação , Filogeografia , Animais , China , Análise por Conglomerados , Feminino , Flavivirus/genética , Genótipo , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Proteínas do Envelope Viral/genética
19.
J Neuroinflammation ; 11: 146, 2014 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-25182681

RESUMO

BACKGROUND: Infection of rabies virus (RABV) causes central nervous system (CNS) dysfunction and results in high mortality in human and animals. However, it is still unclear whether and how CNS inflammation and immune response contribute to RABV infection. METHODS: Suckling mice were intracerebrally infected with attenuated RABV aG and CTN strains, followed by examination of chemokine or cytokine production, inflammatory cell infiltration and neuron apoptosis in the brain. Furthermore, the suckling mice and adult mice that were intracerebrally infected with aG and the adult mice that were intramuscularly infected with street RABV HN10 were treated with CCL5 antagonist (Met-CCL5) daily beginning on day 2 postinfection. The survival rates and inflammation responses in the CNS of these mice were analyzed. RESULTS: Excessive CCL5 in the CNS was associated with CNS dysfunction, inflammation, and macrophage or lymphocyte infiltration after attenuated or street RABV infection. Administration of exogenous CCL5 induced excessive infiltration of immune cells into the CNS and enhanced inflammatory chemokine and cytokine production. Met-CCL5 treatment significantly prolonged survival time of the suckling mice inoculated with aG and adult mice infected with aG and HN10. CONCLUSIONS: These results suggest that CCL5 in the CNS is a key regulator involved in inducing rabies encephalomyelitis. Furthermore, treatment with the CCL5 antagonist Met-CCL5 prolongs survival time of the mice infected with attenuated or street RABVs, which might represent a novel therapeutic strategy to ameliorate RABV infection.


Assuntos
Viroses do Sistema Nervoso Central/terapia , Quimiocina CCL5/antagonistas & inibidores , Imunoterapia/métodos , Raiva/terapia , Animais , Western Blotting , Encéfalo/patologia , Encéfalo/virologia , Viroses do Sistema Nervoso Central/imunologia , Citometria de Fluxo , Camundongos , Raiva/imunologia , Reação em Cadeia da Polimerase em Tempo Real
20.
Langmuir ; 30(21): 6294-301, 2014 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-24828951

RESUMO

A class of new amphiphilic nanocapsules entangled with organometallic coordination polymers has been developed for the first time. Poly(2-(N,N-dimethyl amino)ethyl methacrylate)-b-polystyrene capped with ß-cyclodextrin (ß-CD) (CD-PDMAEMA-b-PS) is first synthesized using sequent RAFT polymerization of styrene and 2-(N,N-dimethyl amino)ethyl methacrylate with xanthate modified ß-CD as chain transfer agent. The end group of ß-CD is allowed to include 4,4'-bipyridine through host-guest inclusion to yield PDMAEMA-b-PS terminated with an inclusion complex of ß-CD and bipyridine (bpy-PDMAEMA-b-PS), which is then used as surfactant to prepare emulsion droplets in toluene/water mixture. Upon addition of Ni(II), bipyridine coordinates with Ni(II) to form coordination polymers in the periphery of emulsion droplets, affording amphiphilic capsules entangled with organometallic coordination polymers, as confirmed by GPC, (1)H NMR, SEM, TEM, DLS, and so on. The organometallic coordination polymer capsules are capable of encapsulating organic cargoes. Interestingly, encapsulated cargoes can be extracted from the capsules without damaging the capsules. Such capsules are potential candidates for encapsulating and controlled release of organic cargoes.


Assuntos
Sistemas de Liberação de Medicamentos , Metacrilatos/química , Nanocápsulas/química , Nanotecnologia/métodos , Nylons/química , Polímeros/química , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Peso Molecular , Níquel/química , Compostos Orgânicos/química , Oxazinas/química , Poliestirenos/química , Piridinas/química , Tensoativos , beta-Ciclodextrinas/química
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