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[PMID]:28895854
[Au] Autor:Rogers GL; Cannon PM
[Ad] Endereço:Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 413A, Los Angeles, CA 90033, USA.
[Ti] Título:Gene Therapy Approaches to Human Immunodeficiency Virus and Other Infectious Diseases.
[So] Source:Hematol Oncol Clin North Am;31(5):883-895, 2017 Oct.
[Is] ISSN:1558-1977
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Advances in gene therapy technologies, particularly in gene editing, are suggesting new avenues for the treatment of human immunodeficiency virus and other infectious diseases. This article outlines recent developments in antiviral gene therapies, including those based on the disruption of entry receptors or that target viral genomes using targeted nucleases, such as the CRISPR/Cas9 system. In addition, new ways to express circulating antiviral factors, such as antibodies, and approaches to harness and engineer the immune system to provide an antiviral effect that is not naturally achieved are described.
[Mh] Termos MeSH primário: Doenças Transmissíveis/terapia
Terapia Genética
Infecções por HIV/terapia
Infecções por HIV/virologia
HIV/genética
[Mh] Termos MeSH secundário: Sistemas CRISPR-Cas
Resistência à Doença/genética
Edição de Genes
Expressão Gênica
Marcação de Genes
Engenharia Genética
Terapia Genética/efeitos adversos
Terapia Genética/métodos
Vetores Genéticos/genética
Genoma Viral
Seres Humanos
Imunomodulação/genética
Receptores de HIV/genética
Receptores de HIV/metabolismo
Transgenes
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Receptors, HIV)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE


  2 / 1344 MEDLINE  
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[PMID]:28863455
[Au] Autor:Amani V; Donson AM; Lummus SC; Prince EW; Griesinger AM; Witt DA; Hankinson TC; Handler MH; Dorris K; Vibhakar R; Foreman NK; Hoffman LM
[Ad] Endereço:Morgan Adams Foundation Pediatric Brain Tumor Research Program; Department of Pathology; and Department of Neurosurgery, University of Colorado Anschutz Medical Campus; and Children's Hospital Colorado, Aurora, Colorado.
[Ti] Título:Characterization of 2 Novel Ependymoma Cell Lines With Chromosome 1q Gain Derived From Posterior Fossa Tumors of Childhood.
[So] Source:J Neuropathol Exp Neurol;76(7):595-604, 2017 Jul 01.
[Is] ISSN:1554-6578
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ependymoma (EPN) is a common brain tumor of childhood that, despite standard surgery and radiation therapy, has a relapse rate of 50%. Clinical trials have been unsuccessful in improving outcome by addition of chemotherapy, and identification of novel therapeutics has been hampered by a lack of in vitro and in vivo models. We describe 2 unique EPN cell lines (811 and 928) derived from recurrent intracranial metastases. Both cell lines harbor the high-risk chromosome 1q gain (1q+) and a derivative chromosome 6, and both are classified as molecular group A according to transcriptomic analysis. Transcriptional enrichment of extracellular matrix-related genes was a common signature of corresponding primary tumors and cell lines in both monolayer and 3D formats. EPN cell lines, when cultured in 3D format, clustered closer to the primary tumors with better fidelity of EPN-specific transcripts than when grown as a monolayer. Additionally, 3D culture revealed ependymal rosette formation and cilia-related ontologies, similar to in situ tumors. Our data confirm the validity of the 811 and 928 cell lines as representative models of intracranial, posterior fossa 1q+ EPN, which holds potential to advance translational science for patients affected by this tumor.
[Mh] Termos MeSH primário: Linhagem Celular Tumoral/patologia
Aberrações Cromossômicas
Cromossomos Humanos Par 1/genética
Ependimoma/patologia
Neoplasias Infratentoriais/genética
Neoplasias Infratentoriais/patologia
[Mh] Termos MeSH secundário: Criança
Análise Citogenética
Proteínas de Ligação a DNA/metabolismo
Ependimoma/genética
Perfilação da Expressão Gênica
Proteína Glial Fibrilar Ácida/metabolismo
Seres Humanos
Imagem Tridimensional
Antígeno Ki-67/metabolismo
Masculino
Análise em Microsséries
Microscopia Confocal
Mucina-1/metabolismo
Proteínas Nucleares/metabolismo
Receptores de HIV/metabolismo
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (C9orf24 protein, human); 0 (DNA-Binding Proteins); 0 (Glial Fibrillary Acidic Protein); 0 (Ki-67 Antigen); 0 (Mucin-1); 0 (Nef receptor); 0 (Nuclear Proteins); 0 (Receptors, HIV); 0 (Transcription Factors)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170903
[St] Status:MEDLINE
[do] DOI:10.1093/jnen/nlx040


  3 / 1344 MEDLINE  
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[PMID]:28659473
[Au] Autor:Arif MS; Hunter J; Léda AR; Zukurov JPL; Samer S; Camargo M; Galinskas J; Kallás EG; Komninakis SV; Janini LM; Sucupira MC; Diaz RS
[Ad] Endereço:Infectious Diseases Division, Federal University of São Paulo, São Paulo, Brazil.
[Ti] Título:Pace of Coreceptor Tropism Switch in HIV-1-Infected Individuals after Recent Infection.
[So] Source:J Virol;91(19), 2017 Oct 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:HIV-1 entry into target cells influences several aspects of HIV-1 pathogenesis, including viral tropism, HIV-1 transmission and disease progression, and response to entry inhibitors. The evolution from CCR5- to CXCR4-using strains in a given human host is still unpredictable. Here we analyzed timing and predictors for coreceptor evolution among recently HIV-1-infected individuals. Proviral DNA was longitudinally evaluated in 66 individuals using Geno2pheno Demographics, viral load, CD4 and CD8 T cell counts, CCR5Δ32 polymorphisms, GB virus C (GBV-C) coinfection, and HLA profiles were also evaluated. Ultradeep sequencing was performed on initial samples from 11 selected individuals. A tropism switch from CCR5- to CXCR4-using strains was identified in 9/49 (18.4%) individuals. Only a low baseline false-positive rate (FPR) was found to be a significant tropism switch predictor. No minor CXCR4-using variants were identified in initial samples of 4 of 5 R5/non-R5 switchers. Logistic regression analysis showed that patients with an FPR of >40.6% at baseline presented a stable FPR over time whereas lower FPRs tend to progressively decay, leading to emergence of CXCR4-using strains, with a mean evolution time of 27.29 months (range, 8.90 to 64.62). An FPR threshold above 40.6% determined by logistic regression analysis may make it unnecessary to further determine tropism for prediction of disease progression related to emergence of X4 strains or use of CCR5 antagonists. The detection of variants with intermediate FPRs and progressive FPR decay over time not only strengthens the power of Geno2pheno in predicting HIV tropism but also indirectly confirms a continuous evolution from earlier R5 variants toward CXCR4-using strains. The introduction of CCR5 antagonists in the antiretroviral arsenal has sparked interest in coreceptors utilized by HIV-1. Despite concentrated efforts, viral and human host features predicting tropism switch are still poorly understood. Limited longitudinal data are available to assess the influence that these factors have on predicting tropism switch and disease progression. The present study describes longitudinal tropism evolution in a group of recently HIV-infected individuals to determine the prevalence and potential correlates of tropism switch. We demonstrated here that a low baseline FPR determined by the Geno2pheno algorithm can predict tropism evolution from CCR5 to CXCR4 coreceptor use.
[Mh] Termos MeSH primário: Vírus GB C/metabolismo
Infecções por HIV/transmissão
HIV-1/metabolismo
Receptores CCR5/metabolismo
Receptores CXCR4/metabolismo
Receptores de HIV/metabolismo
Tropismo Viral/fisiologia
[Mh] Termos MeSH secundário: Adulto
Contagem de Linfócito CD4
Relação CD4-CD8
Coinfecção/virologia
Reações Falso-Positivas
Feminino
Infecções por HIV/virologia
HIV-1/genética
Seres Humanos
Masculino
Meia-Idade
Carga Viral/imunologia
Ligação Viral
Internalização do Vírus
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CCR5 protein, human); 0 (CXCR4 protein, human); 0 (Receptors, CCR5); 0 (Receptors, CXCR4); 0 (Receptors, HIV)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170630
[St] Status:MEDLINE


  4 / 1344 MEDLINE  
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[PMID]:28521215
[Au] Autor:Espy N; Pacheco B; Sodroski J
[Ad] Endereço:Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
[Ti] Título:Adaptation of HIV-1 to cells with low expression of the CCR5 coreceptor.
[So] Source:Virology;508:90-107, 2017 Aug.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The binding of the human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer ((gp120/gp41) ) to the receptors CD4 and CCR5 triggers virus entry into host cells. To identify Env regions that respond to CCR5 binding, HIV-1 was serially passaged on a CD4-positive canine cell line expressing progressively lower levels of CCR5. HIV-1 replication was observed in cells expressing ~1300 CCR5 molecules/cell. Env changes that conferred this low-CCR5 replication phenotype were located outside of the known CCR5-binding region of the gp120 Env subunit and did not apparently increase CCR5 binding affinity. The adaptation-associated changes, located in the gp120 α1 helix and in the gp41 HR1 heptad repeat and membrane-proximal external region (MPER), enhanced HIV-1 replication in cells at all levels of CCR5 expression. The adapted Envs exhibited a greater propensity to undergo conformational changes, as evidenced by increased exposure of conserved regions near the CD4- and CCR5-binding sites.
[Mh] Termos MeSH primário: Proteína gp120 do Envelope de HIV/metabolismo
Infecções por HIV/metabolismo
HIV-1/metabolismo
Receptores CCR5/metabolismo
Receptores de HIV/metabolismo
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Antígenos CD4/genética
Antígenos CD4/metabolismo
Proteína gp120 do Envelope de HIV/química
Proteína gp120 do Envelope de HIV/genética
Infecções por HIV/genética
Infecções por HIV/virologia
HIV-1/química
HIV-1/genética
Seres Humanos
Ligação Proteica
Receptores CCR5/genética
Receptores de HIV/genética
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CD4 Antigens); 0 (HIV Envelope Protein gp120); 0 (Receptors, CCR5); 0 (Receptors, HIV)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170519
[St] Status:MEDLINE


  5 / 1344 MEDLINE  
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[PMID]:28060951
[Au] Autor:Chinnapaiyan S; Parira T; Dutta R; Agudelo M; Morris A; Nair M; Unwalla HJ
[Ad] Endereço:Department of Immunology, Institute of Neuroimmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University. Miami, Florida, United States of America.
[Ti] Título:HIV Infects Bronchial Epithelium and Suppresses Components of the Mucociliary Clearance Apparatus.
[So] Source:PLoS One;12(1):e0169161, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recurrent lung infections and pneumonia are emerging as significant comorbidities in the HIV-infected population in the era of combination antiretroviral therapy (cART). HIV infection has been reported to suppress nasal mucociliary clearance (MCC). Since the primary components driving nasal MCC and bronchial MCC are identical, it is possible that bronchial MCC is affected as well. Effective MCC requires optimal ciliary beating which depends on the maintenance of the airway surface liquid (ASL), a function of cystic fibrosis transmembrane conductance regulator (CFTR) activity and the integrity of the signaling mechanism that regulates ciliary beating and fluid secretion. Impairment of either component of the MCC apparatus can compromise its efficacy and promote microbial colonization. We demonstrate that primary bronchial epithelium expresses HIV receptor CD4 and co-receptors CCR5 and CXCR4 and can be infected by both R5 and X4 tropic strains of HIV. We show that HIV Tat suppresses CFTR biogenesis and function in primary bronchial epithelial cells by a pathway involving TGF-ß signaling. HIV infection also interferes with bronchial epithelial cell differentiation and suppresses ciliogenesis. These findings suggest that HIV infection suppresses tracheobronchial mucociliary clearance and this may predispose HIV-infected patients to recurrent lung infections, pneumonia and chronic bronchitis.
[Mh] Termos MeSH primário: Infecções por HIV/imunologia
Infecções por HIV/virologia
HIV/fisiologia
Depuração Mucociliar/imunologia
Mucosa Respiratória/imunologia
Mucosa Respiratória/virologia
[Mh] Termos MeSH secundário: Cílios/patologia
Cílios/virologia
Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo
Células Epiteliais/metabolismo
Células Epiteliais/virologia
Expressão Gênica
Infecções por HIV/genética
Infecções por HIV/metabolismo
Seres Humanos
Imunidade Inata
Provírus
RNA Viral
Receptores de HIV/genética
Receptores de HIV/metabolismo
Mucosa Respiratória/metabolismo
Transcrição Reversa
Transdução de Sinais
Fator de Crescimento Transformador beta/metabolismo
Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Viral); 0 (Receptors, HIV); 0 (Transforming Growth Factor beta); 0 (tat Gene Products, Human Immunodeficiency Virus); 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170815
[Lr] Data última revisão:
170815
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170107
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0169161


  6 / 1344 MEDLINE  
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[PMID]:28053103
[Au] Autor:Jacobs ES; Keating SM; Abdel-Mohsen M; Gibb SL; Heitman JW; Inglis HC; Martin JN; Zhang J; Kaidarova Z; Deng X; Wu S; Anastos K; Crystal H; Villacres MC; Young M; Greenblatt RM; Landay AL; Gange SJ; Deeks SG; Golub ET; Pillai SK; Norris PJ
[Ad] Endereço:Blood Systems Research Institute, San Francisco, California, USA.
[Ti] Título:Cytokines Elevated in HIV Elite Controllers Reduce HIV Replication and Modulate HIV Restriction Factor Expression.
[So] Source:J Virol;91(6), 2017 Mar 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A subset of HIV-infected individuals termed elite controllers (ECs) maintain CD4 T cell counts and control viral replication in the absence of antiretroviral therapy (ART). Systemic cytokine responses may differentiate ECs from subjects with uncontrolled viral replication or from those who require ART to suppress viral replication. We measured 87 cytokines in four groups of women: 73 ECs, 42 with pharmacologically suppressed viremia (ART), 42 with uncontrolled viral replication (noncontrollers [NCs]), and 48 HIV-uninfected (NEG) subjects. Four cytokines were elevated in ECs but not NCs or ART subjects: CCL14, CCL21, CCL27, and XCL1. In addition, median stromal cell-derived factor-1 (SDF-1) levels were 43% higher in ECs than in NCs. The combination of the five cytokines suppressed R5 and X4 virus replication in resting CD4 T cells, and individually SDF-1ß, CCL14, and CCL27 suppressed R5 virus replication, while SDF-1ß, CCL21, and CCL14 suppressed X4 virus replication. Functional studies revealed that the combination of the five cytokines upregulated CD69 and CCR5 and downregulated CXCR4 and CCR7 on CD4 T cells. The CD69 and CXCR4 effects were driven by SDF-1, while CCL21 downregulated CCR7. The combination of the EC-associated cytokines induced expression of the anti-HIV host restriction factors IFITM1 and IFITM2 and suppressed expression of RNase L and SAMHD1. These results identify a set of cytokines that are elevated in ECs and define their effects on cellular activation, HIV coreceptor expression, and innate restriction factor expression. This cytokine pattern may be a signature characteristic of HIV-1 elite control, potentially important for HIV therapeutic and curative strategies. Approximately 1% of people infected with HIV control virus replication without taking antiviral medications. These subjects, termed elite controllers (ECs), are known to have stronger immune responses targeting HIV than the typical HIV-infected subject, but the exact mechanisms of how their immune responses control infection are not known. In this study, we identified five soluble immune signaling molecules (cytokines) in the blood that were higher in ECs than in subjects with typical chronic HIV infection. We demonstrated that these cytokines can activate CD4 T cells, the target cells for HIV infection. Furthermore, these five EC-associated cytokines could change expression levels of intrinsic resistance factors, or molecules inside the target cell that fight HIV infection. This study is significant in that it identified cytokines elevated in subjects with a good immune response against HIV and defined potential mechanisms as to how these cytokines could induce resistance to the virus in target cells.
[Mh] Termos MeSH primário: Citocinas/metabolismo
Infecções por HIV/imunologia
HIV/imunologia
HIV/fisiologia
Replicação Viral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adulto
Antígenos de Diferenciação/biossíntese
Linfócitos T CD4-Positivos/virologia
Feminino
Regulação da Expressão Gênica
Sobreviventes de Longo Prazo ao HIV
Seres Humanos
Proteínas de Membrana/biossíntese
Meia-Idade
Plasma/química
Receptores de HIV/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Differentiation); 0 (Cytokines); 0 (IFITM2 protein, human); 0 (Membrane Proteins); 0 (Receptors, HIV); 0 (leu-13 antigen)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170106
[St] Status:MEDLINE


  7 / 1344 MEDLINE  
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[PMID]:27815696
[Au] Autor:Wei XM; Xu HF; Cheng XD; Bu N; Zhou HZ
[Ad] Endereço:Department of Laboratory Diagnosis, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, People's Republic of China.
[Ti] Título:Position 22 of the V3 loop is associated with HIV infectivity.
[So] Source:Arch Virol;162(3):637-643, 2017 Mar.
[Is] ISSN:1432-8798
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Human immunodeficiency virus subtype 1B (HIV-1B) binds to the CD4 receptor and co-receptor CCR5 or CXCR4 to enter T lymphocytes. The amino acid sequence of the HIV envelope glycoprotein V3 region determines the co-receptor tropism, thereby influencing the infectivity of the virus. Our research group previously found that the amino acid at position 22 of the V3 region may affect the infectivity of the virus, and in this study, we tested this hypothesis. We constructed pseudoviruses by changing the amino acids at position 22 of the V3 region in CCR5-tropic and CXCR4-tropic viruses and tested their infectivity. When the amino acid at V3 position 22 was altered in the CCR5- and CXCR4-tropic viruses, their ability to infect cells decreased to 20.6% and 17.14%, respectively. Therefore, we propose that residue 22 in the V3 region of subtype HIV-1B significantly influences the infectivity of the virus.
[Mh] Termos MeSH primário: Proteína gp120 do Envelope de HIV/química
Proteína gp120 do Envelope de HIV/metabolismo
Infecções por HIV/metabolismo
HIV-1/metabolismo
HIV-1/patogenicidade
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Linhagem Celular
Proteína gp120 do Envelope de HIV/genética
Infecções por HIV/genética
Infecções por HIV/virologia
HIV-1/química
HIV-1/genética
Seres Humanos
Ligação Proteica
Receptores CCR5/genética
Receptores CCR5/metabolismo
Receptores CXCR4/genética
Receptores CXCR4/metabolismo
Receptores de HIV/genética
Receptores de HIV/metabolismo
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CXCR4 protein, human); 0 (HIV Envelope Protein gp120); 0 (Receptors, CCR5); 0 (Receptors, CXCR4); 0 (Receptors, HIV)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170321
[Lr] Data última revisão:
170321
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161106
[St] Status:MEDLINE
[do] DOI:10.1007/s00705-016-3138-7


  8 / 1344 MEDLINE  
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[PMID]:27749600
[Au] Autor:Shi B; Li J; Shi X; Jia W; Wen Y; Hu X; Zhuang F; Xi J; Zhang L
[Ad] Endereço:*Comprehensive AIDS Research Center and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, China; †Department of Biomedical Engineering, Peking University, Beijing, China; and ‡ViewSolid Biotech, Beijing, China.
[Ti] Título:TALEN-Mediated Knockout of CCR5 Confers Protection Against Infection of Human Immunodeficiency Virus.
[So] Source:J Acquir Immune Defic Syndr;74(2):229-241, 2017 Feb 01.
[Is] ISSN:1944-7884
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Transcription activator-like effector nuclease (TALEN) represents a valuable tool for genomic engineering due to its single-nucleotide precision, high nuclease activity, and low cytotoxicity. We report here systematic design and characterization of 28 novel TALENs targeting multiple regions of CCR5 gene (CCR5-TALEN) which encodes the co-receptor critical for entry of human immunodeficiency virus type I (HIV-1). By systemic characterization of these CCR5-TALENs, we have identified one (CCR5-TALEN-515) with higher nuclease activity, specificity, and lower cytotoxicity compared with zinc-finger nuclease (CCR5-ZFN) currently undergoing clinical trials. Sequence analysis of target cell line GHOST-CCR5-CXCR4 and human primary CD4 T cells showed that the double-strand breaks at the TALEN targeted sites resulted in truncated or nonfunctional CCR5 proteins thereby conferring protection against HIV-1 infection in vitro. None of the CCR5-TALENs had detectable levels of off-target nuclease activity against the homologous region in CCR2 although substantial level was identified for CCR5-ZFN in the primary CD4 T cells. Our results suggest that the CCR5-TALENs identified here are highly functional nucleases that produce protective genetic alterations to human CCR5. Application of these TALENs directly to the primary CD4 T cells and CD34 hematopoietic stem cells (HSCs) of infected individuals could help to create an immune system resistant to HIV-1 infection, recapitulating the success of "Berlin patient" and serving as an essential first step towards a "functional" cure of AIDS.
[Mh] Termos MeSH primário: Técnicas de Inativação de Genes/métodos
HIV-1/fisiologia
Receptores CCR5/deficiência
Receptores de HIV/deficiência
Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Adulto
Linfócitos T CD4-Positivos/virologia
Células Cultivadas
HIV-1/crescimento & desenvolvimento
Seres Humanos
Deleção de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CCR5 protein, human); 0 (Receptors, CCR5); 0 (Receptors, HIV); EC 3.1.- (Transcription Activator-Like Effector Nucleases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:161018
[St] Status:MEDLINE
[do] DOI:10.1097/QAI.0000000000001190


  9 / 1344 MEDLINE  
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[PMID]:27919079
[Au] Autor:Ribeiro CM; Sarrami-Forooshani R; Setiawan LC; Zijlstra-Willems EM; van Hamme JL; Tigchelaar W; van der Wel NN; Kootstra NA; Gringhuis SI; Geijtenbeek TB
[Ad] Endereço:Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
[Ti] Título:Receptor usage dictates HIV-1 restriction by human TRIM5α in dendritic cell subsets.
[So] Source:Nature;540(7633):448-452, 2016 12 15.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The most prevalent route of HIV-1 infection is across mucosal tissues after sexual contact. Langerhans cells (LCs) belong to the subset of dendritic cells (DCs) that line the mucosal epithelia of vagina and foreskin and have the ability to sense and induce immunity to invading pathogens. Anatomical and functional characteristics make LCs one of the primary targets of HIV-1 infection. Notably, LCs form a protective barrier against HIV-1 infection and transmission. LCs restrict HIV-1 infection through the capture of HIV-1 by the C-type lectin receptor Langerin and subsequent internalization into Birbeck granules. However, the underlying molecular mechanism of HIV-1 restriction in LCs remains unknown. Here we show that human E3-ubiquitin ligase tri-partite-containing motif 5α (TRIM5α) potently restricts HIV-1 infection of LCs but not of subepithelial DC-SIGN DCs. HIV-1 restriction by TRIM5α was thus far considered to be reserved to non-human primate TRIM5α orthologues, but our data strongly suggest that human TRIM5α is a cell-specific restriction factor dependent on C-type lectin receptor function. Our findings highlight the importance of HIV-1 binding to Langerin for the routeing of HIV-1 into the human TRIM5α-mediated restriction pathway. TRIM5α mediates the assembly of an autophagy-activating scaffold to Langerin, which targets HIV-1 for autophagic degradation and prevents infection of LCs. By contrast, HIV-1 binding to DC-SIGN DCs leads to disassociation of TRIM5α from DC-SIGN, which abrogates TRIM5α restriction. Thus, our data strongly suggest that restriction by human TRIM5α is controlled by C-type-lectin-receptor-dependent uptake of HIV-1, dictating protection or infection of human DC subsets. Therapeutic interventions that incorporate C-type lectin receptors and autophagy-targeting strategies could thus provide cell-mediated resistance to HIV-1 in humans.
[Mh] Termos MeSH primário: Antígenos CD/metabolismo
Autofagia
Proteínas de Transporte/metabolismo
HIV-1/fisiologia
Células de Langerhans/metabolismo
Células de Langerhans/virologia
Lectinas Tipo C/metabolismo
Lectinas de Ligação a Manose/metabolismo
Receptores de HIV/metabolismo
[Mh] Termos MeSH secundário: Moléculas de Adesão Celular/metabolismo
Linhagem Celular
Infecções por HIV/imunologia
Infecções por HIV/prevenção & controle
Infecções por HIV/transmissão
HIV-1/imunologia
Interações Hospedeiro-Patógeno
Seres Humanos
Imunidade nas Mucosas
Células de Langerhans/citologia
Células de Langerhans/imunologia
Receptores de Superfície Celular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, CD); 0 (CD207 protein, human); 0 (Carrier Proteins); 0 (Cell Adhesion Molecules); 0 (DC-specific ICAM-3 grabbing nonintegrin); 0 (Lectins, C-Type); 0 (Mannose-Binding Lectins); 0 (Receptors, Cell Surface); 0 (Receptors, HIV); 0 (TRIM5 protein, human)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170603
[Lr] Data última revisão:
170603
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161206
[St] Status:MEDLINE
[do] DOI:10.1038/nature20567


  10 / 1344 MEDLINE  
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Fotocópia
[PMID]:27905841
[Au] Autor:Symonds G; Bartlett JS; Kiem HP; Tsie M; Breton L
[Ad] Endereço:1 Calimmune, Inc. , Tucson, Arizona.
[Ti] Título:Cell-Delivered Entry Inhibitors for HIV-1: CCR5 Downregulation and Blocking Virus/Membrane Fusion in Defending the Host Cell Population.
[So] Source:AIDS Patient Care STDS;30(12):545-550, 2016 Dec.
[Is] ISSN:1557-7449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:HIV-1 infection requires the presence of the CD4 receptor on the target cell surface and a coreceptor, predominantly CC-chemokine receptor 5 (CCR5). It has been shown that individuals who are homozygous for a defective CCR5 gene are protected from HIV-1 infection. A novel self-inactivating lentiviral vector LVsh5/C46 (Cal-1) has been engineered to block HIV-1 infection with two viral entry inhibitors, conferring resistance to HIV-1 infection from both CCR5 and CXCR4 tropic strains. Cal-1 encodes a short hairpin RNA (sh5) to downregulate CCR5 and C46, an HIV-1 fusion inhibitor. Gene therapy by Cal-1 is aimed at transducing CD4 T cells and CD34 hematopoietic stem/progenitor cells in an autologous transplant setting. Pre-clinical safety and efficacy studies in vitro and in vivo (humanized mouse model and nonhuman primates) have shown that Cal-1 is safe with no indication of any toxicity risk and acts to decrease viral load and increase CD4 counts. Two clinical trials are underway using Cal-1: a phase I/II study to assess safety and feasibility in an adult HIV-1-positive population not on antiretroviral therapy (ART); and a second Fred Hutchinson Investigator Initiated phase I study to assess safety and feasibility in adults with HIV-1-associated non-Hodgkin or Hodgkin lymphoma.
[Mh] Termos MeSH primário: Terapia Genética/métodos
Infecções por HIV/terapia
HIV-1/fisiologia
Fusão de Membrana
Receptores CCR5
Receptores de HIV/antagonistas & inibidores
Proteínas Recombinantes de Fusão/biossíntese
[Mh] Termos MeSH secundário: Adulto
Animais
Terapia Biológica/métodos
Antagonistas dos Receptores CCR5
Contagem de Linfócito CD4
Ensaios Clínicos como Assunto
Regulação para Baixo
Infecções por HIV/genética
Infecções por HIV/virologia
HIV-1/genética
Células-Tronco Hematopoéticas
Seres Humanos
Receptores CCR5/biossíntese
Receptores CXCR4
Proteínas Recombinantes de Fusão/genética
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (C46 HIV-1 fusion inhibitory peptide); 0 (CCR5 Receptor Antagonists); 0 (CCR5 protein, human); 0 (CXCR4 protein, human); 0 (Receptors, CCR5); 0 (Receptors, CXCR4); 0 (Receptors, HIV); 0 (Recombinant Fusion Proteins)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:161202
[St] Status:MEDLINE



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