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  1 / 1933 MEDLINE  
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[PMID]:28458036
[Au] Autor:Meador LR; Kessans SA; Kilbourne J; Kibler KV; Pantaleo G; Roderiguez ME; Blattman JN; Jacobs BL; Mor TS
[Ad] Endereço:Ira A. Fulton School of Engineering, Arizona State University, Tempe, AZ, USA; Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ, USA.
[Ti] Título:A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles.
[So] Source:Virology;507:242-256, 2017 07.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation. We tested different prime/boost combinations of these components in mice and showed that the group primed with NYVAC-KC and boosted with both the viral vectors and plant-produced VLPs have the most robust Gag-specific CD8 T cell responses, at 12.7% of CD8 T cells expressing IFN-γ in response to stimulation with five Gag epitopes. The same immunization group elicited the best systemic and mucosal antibody responses to Gag and dgp41 with a bias towards IgG1.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/administração & dosagem
Proteína gp41 do Envelope de HIV/imunologia
Infecções por HIV/imunologia
HIV-1/imunologia
Imunização/métodos
Tabaco/metabolismo
Vírus Vaccinia/fisiologia
Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/imunologia
Animais
Anticorpos Neutralizantes/imunologia
Formação de Anticorpos
Feminino
Vetores Genéticos/genética
Vetores Genéticos/fisiologia
Anticorpos Anti-HIV/imunologia
Proteína gp41 do Envelope de HIV/administração & dosagem
Proteína gp41 do Envelope de HIV/genética
Infecções por HIV/prevenção & controle
Infecções por HIV/virologia
HIV-1/genética
Seres Humanos
Imunização Secundária
Camundongos
Camundongos Endogâmicos C57BL
Tabaco/genética
Tabaco/virologia
Vacinas de Partículas Semelhantes a Vírus/genética
Vacinas de Partículas Semelhantes a Vírus/imunologia
Vírus Vaccinia/genética
Replicação Viral
Produtos do Gene gag do Vírus da Imunodeficiência Humana/administração & dosagem
Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (HIV Antibodies); 0 (HIV Envelope Protein gp41); 0 (Vaccines, Virus-Like Particle); 0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


  2 / 1933 MEDLINE  
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[PMID]:28454672
[Au] Autor:Tang J; Jones SA; Jeffrey JL; Miranda SR; Galardi CM; Irlbeck DM; Brown KW; McDanal CB; Johns BA
[Ad] Endereço:GlaxoSmithKline Research & Development, Infectious Diseases Therapy Area Unit, Research Triangle Park, NC 27709, USA. Electronic address: jun.x.tang@gsk.com.
[Ti] Título:Discovery of a novel and potent class of anti-HIV-1 maturation inhibitors with improved virology profile against gag polymorphisms.
[So] Source:Bioorg Med Chem Lett;27(12):2689-2694, 2017 06 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A new class of betulin-derived α-keto amides was identified as HIV-1 maturation inhibitors. Through lead optimization, GSK8999 was identified with IC values of 17nM, 23nM, 25nM, and 8nM for wild type, Q369H, V370A, and T371A respectively. When tested in a panel of 62 HIV-1 isolates covering a diversity of CA-SP1 genotypes including A, AE, B, C, and G using a PBMC based assay, GSK8999 was potent against 57 of 62 isolates demonstrating an improvement over the first generation maturation inhibitor BVM. The data disclosed here also demonstrated that the new α-keto amide GSK8999 has a mechanism of action consistent with inhibition of the proteolytic cleavage of CA-SP1.
[Mh] Termos MeSH primário: Amidas/farmacologia
Fármacos Anti-HIV/farmacologia
Descoberta de Drogas
HIV-1/efeitos dos fármacos
Polimorfismo Genético/efeitos dos fármacos
Triterpenos/farmacologia
Produtos do Gene gag do Vírus da Imunodeficiência Humana/antagonistas & inibidores
[Mh] Termos MeSH secundário: Amidas/síntese química
Amidas/química
Fármacos Anti-HIV/síntese química
Fármacos Anti-HIV/química
Relação Dose-Resposta a Droga
Testes de Sensibilidade Microbiana
Estrutura Molecular
Polimorfismo Genético/genética
Relação Estrutura-Atividade
Triterpenos/química
Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Anti-HIV Agents); 0 (Triterpenes); 0 (gag Gene Products, Human Immunodeficiency Virus); 6W70HN7X7O (betulin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171124
[Lr] Data última revisão:
171124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


  3 / 1933 MEDLINE  
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[PMID]:29045410
[Au] Autor:Dapp MJ; Kober KM; Chen L; Westfall DH; Wong K; Zhao H; Hall BM; Deng W; Sibley T; Ghorai S; Kim K; Chen N; McHugh S; Au L; Cohen M; Anastos K; Mullins JI
[Ad] Endereço:Department of Microbiology, University of Washington School of Medicine, Seattle, Washington, United States of America.
[Ti] Título:Patterns and rates of viral evolution in HIV-1 subtype B infected females and males.
[So] Source:PLoS One;12(10):e0182443, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS. However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men. We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART). This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes. No differences in ensuing nucleotide substitution rates were found between the female and male cohorts studied herein. As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region. These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.
[Mh] Termos MeSH primário: Infecções por HIV/virologia
HIV-1/fisiologia
Caracteres Sexuais
[Mh] Termos MeSH secundário: Estudos de Coortes
Progressão da Doença
Evolução Molecular
Feminino
Glicosilação
Proteína gp120 do Envelope de HIV/genética
Infecções por HIV/genética
Seres Humanos
Funções Verossimilhança
Masculino
Nucleotídeos/genética
Filogenia
Fatores de Tempo
Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HIV Envelope Protein gp120); 0 (Nucleotides); 0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171019
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182443


  4 / 1933 MEDLINE  
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[PMID]:29023474
[Au] Autor:Kiwuwa-Muyingo S; Nazziwa J; Ssemwanga D; Ilmonen P; Njai H; Ndembi N; Parry C; Kitandwe PK; Gershim A; Mpendo J; Neilsen L; Seeley J; Seppälä H; Lyagoba F; Kamali A; Kaleebu P
[Ad] Endereço:Medical Research Council/Uganda Virus Research Institute, Research Unit on AIDS, Entebbe, Uganda.
[Ti] Título:HIV-1 transmission networks in high risk fishing communities on the shores of Lake Victoria in Uganda: A phylogenetic and epidemiological approach.
[So] Source:PLoS One;12(10):e0185818, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Fishing communities around Lake Victoria in sub-Saharan Africa have been characterised as a population at high risk of HIV-infection. METHODS: Using data from a cohort of HIV-positive individuals aged 13-49 years, enrolled from 5 fishing communities on Lake Victoria between 2009-2011, we sought to identify factors contributing to the epidemic and to understand the underlying structure of HIV transmission networks. Clinical and socio-demographic data were combined with HIV-1 phylogenetic analyses. HIV-1 gag-p24 and env-gp-41 sub-genomic fragments were amplified and sequenced from 283 HIV-1-infected participants. Phylogenetic clusters with ≥2 highly related sequences were defined as transmission clusters. Logistic regression models were used to determine factors associated with clustering. RESULTS: Altogether, 24% (n = 67/283) of HIV positive individuals with sequences fell within 34 phylogenetically distinct clusters in at least one gene region (either gag or env). Of these, 83% occurred either within households or within community; 8/34 (24%) occurred within household partnerships, and 20/34 (59%) within community. 7/12 couples (58%) within households clustered together. Individuals in clusters with potential recent transmission (11/34) were more likely to be younger 71% (15/21) versus 46% (21/46) in un-clustered individuals and had recently become resident in the community 67% (14/21) vs 48% (22/46). Four of 11 (36%) potential transmission clusters included incident-incident transmissions. Independently, clustering was less likely in HIV subtype D (adjusted Odds Ratio, aOR = 0.51 [95% CI 0.26-1.00]) than A and more likely in those living with an HIV-infected individual in the household (aOR = 6.30 [95% CI 3.40-11.68]). CONCLUSIONS: A large proportion of HIV sexual transmissions occur within house-holds and within communities even in this key mobile population. The findings suggest localized HIV transmissions and hence a potential benefit for the test and treat approach even at a community level, coupled with intensified HIV counselling to identify early infections.
[Mh] Termos MeSH primário: Infecções por HIV
HIV-1/genética
Filogenia
Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Fatores Etários
Feminino
Infecções por HIV/epidemiologia
Infecções por HIV/genética
Infecções por HIV/transmissão
Seres Humanos
Lagos
Masculino
Meia-Idade
Uganda/epidemiologia
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (env Gene Products, Human Immunodeficiency Virus); 0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171022
[Lr] Data última revisão:
171022
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171013
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185818


  5 / 1933 MEDLINE  
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[PMID]:28922356
[Au] Autor:Liu Y; Zou X
[Ad] Endereço:School of Mathematics and Statistics, Wuhan University, Computational Science Hubei Key Laboratory, Wuhan University, Wuhan, China.
[Ti] Título:Mathematical modeling and quantitative analysis of HIV-1 Gag trafficking and polymerization.
[So] Source:PLoS Comput Biol;13(9):e1005733, 2017 Sep.
[Is] ISSN:1553-7358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gag, as the major structural protein of HIV-1, is necessary for the assembly of the HIV-1 sphere shell. An in-depth understanding of its trafficking and polymerization is important for gaining further insights into the mechanisms of HIV-1 replication and the design of antiviral drugs. We developed a mathematical model to simulate two biophysical processes, specifically Gag monomer and dimer transport in the cytoplasm and the polymerization of monomers to form a hexamer underneath the plasma membrane. Using experimental data, an optimization approach was utilized to identify the model parameters, and the identifiability and sensitivity of these parameters were then analyzed. Using our model, we analyzed the weight of the pathways involved in the polymerization reactions and concluded that the predominant pathways for the formation of a hexamer might be the polymerization of two monomers to form a dimer, the polymerization of a dimer and a monomer to form a trimer, and the polymerization of two trimers to form a hexamer. We then deduced that the dimer and trimer intermediates might be crucial in hexamer formation. We also explored four theoretical combined methods for Gag suppression, and hypothesized that the N-terminal glycine residue of the MA domain of Gag might be a promising drug target. This work serves as a guide for future theoretical and experimental efforts aiming to understand HIV-1 Gag trafficking and polymerization, and might help accelerate the efficiency of anti-AIDS drug design.
[Mh] Termos MeSH primário: Infecções por HIV/virologia
HIV-1/metabolismo
HIV-1/fisiologia
Produtos do Gene gag do Vírus da Imunodeficiência Humana/química
Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo
[Mh] Termos MeSH secundário: Biologia Computacional
Infecções por HIV/metabolismo
Interações Hospedeiro-Patógeno/fisiologia
Seres Humanos
Modelos Biológicos
Polimerização
Transporte Proteico
Montagem de Vírus
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170919
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pcbi.1005733


  6 / 1933 MEDLINE  
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[PMID]:28878089
[Au] Autor:Leitman EM; Willberg CB; Tsai MH; Chen H; Buus S; Chen F; Riddell L; Haas D; Fellay J; Goedert JJ; Piechocka-Trocha A; Walker BD; Martin J; Deeks S; Wolinsky SM; Martinson J; Martin M; Qi Y; Sáez-Cirión A; Yang OO; Matthews PC; Carrington M; Goulder PJR
[Ad] Endereço:Department of Paediatrics, University of Oxford, Oxford, United Kingdom ellen_leitman@hms.harvard.edu.
[Ti] Título:HLA-B*14:02-Restricted Env-Specific CD8 T-Cell Activity Has Highly Potent Antiviral Efficacy Associated with Immune Control of HIV Infection.
[So] Source:J Virol;91(22), 2017 Nov 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8 T-cell responses. We here focus on HLA-B*14, which protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response is Env specific (ERYLKDQQL, HLA-B*14-EL9). A subdominant HLA-B*14-restricted response targets Gag (DRYFKTLRA, HLA-B*14-DA9). Using HLA-B*14/peptide-saporin-conjugated tetramers, we show that HLA-B*14-EL9 is substantially more potent at inhibiting viral replication than HLA-B*14-DA9. HLA-B*14-EL9 also has significantly higher functional avidity ( < 0.0001) and drives stronger selection pressure on the virus than HLA-B*14-DA9. However, these differences were HLA-B*14 subtype specific, applying only to HLA-B*14:02 and not to HLA-B*14:01. Furthermore, the HLA-B*14-associated protection against HIV disease progression is significantly greater for HLA-B*14:02 than for HLA-B*14:01, consistent with the superior antiviral efficacy of the HLA-B*14-EL9 response. Thus, although Gag-specific CD8 T-cell responses may usually have greater anti-HIV efficacy, factors independent of protein specificity, including functional avidity of individual responses, are also critically important to immune control of HIV. In HIV infection, although cytotoxic T lymphocytes (CTL) play a potentially critical role in eradication of viral reservoirs, the features that constitute an effective response remain poorly defined. We focus on HLA-B*14, unique among HLAs associated with control of HIV in that the dominant CTL response is Env specific, not Gag specific. We demonstrate that Env-specific HLA-B*14-restricted activity is substantially more efficacious than the subdominant HLA-B*14-restricted Gag response. Env immunodominance over Gag and strong Env-mediated selection pressure on HIV are observed only in subjects expressing HLA-B*14:02, and not HLA-B*14:01. This reflects the increased functional avidity of the Env response over Gag, substantially more marked for HLA-B*14:02. Finally, we show that HLA-B*14:02 is significantly more strongly associated with viremic control than HLA-B*14:01. These findings indicate that, although Gag-specific CTL may usually have greater anti-HIV efficacy than Env responses, factors independent of protein specificity, including functional avidity, may carry greater weight in mediating effective control of HIV.
[Mh] Termos MeSH primário: Proteína gp160 do Envelope de HIV/imunologia
Infecções por HIV/imunologia
HIV-1/imunologia
Antígeno HLA-B14/imunologia
Imunidade Celular
Peptídeos/imunologia
Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia
[Mh] Termos MeSH secundário: Adulto
Linfócitos T CD8-Positivos
Infecções por HIV/patologia
Infecções por HIV/terapia
Seres Humanos
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (HIV Envelope Protein gp160); 0 (HLA-B*14:01 antigen); 0 (HLA-B*14:02 antigen); 0 (HLA-B14 Antigen); 0 (Peptides); 0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE


  7 / 1933 MEDLINE  
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[PMID]:28873410
[Au] Autor:Saito H; Takeuchi H; Masuda T; Noda T; Yamaoka S
[Ad] Endereço:Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
[Ti] Título:N-terminally truncated POM121C inhibits HIV-1 replication.
[So] Source:PLoS One;12(9):e0182434, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recent studies have identified host cell factors that regulate early stages of HIV-1 infection including viral cDNA synthesis and orientation of the HIV-1 capsid (CA) core toward the nuclear envelope, but it remains unclear how viral DNA is imported through the nuclear pore and guided to the host chromosomal DNA. Here, we demonstrate that N-terminally truncated POM121C, a component of the nuclear pore complex, blocks HIV-1 infection. This truncated protein is predominantly localized in the cytoplasm, does not bind to CA, does not affect viral cDNA synthesis, reduces the formation of 2-LTR and diminished the amount of integrated proviral DNA. Studies with an HIV-1-murine leukemia virus (MLV) chimeric virus carrying the MLV-derived Gag revealed that Gag is a determinant of this inhibition. Intriguingly, mutational studies have revealed that the blockade by N-terminally-truncated POM121C is closely linked to its binding to importin-ß/karyopherin subunit beta 1 (KPNB1). These results indicate that N-terminally-truncated POM121C inhibits HIV-1 infection after completion of reverse transcription and before integration, and suggest an important role for KPNB1 in HIV-1 replication.
[Mh] Termos MeSH primário: HIV-1/fisiologia
Glicoproteínas de Membrana/farmacologia
Replicação Viral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular/efeitos dos fármacos
Núcleo Celular/efeitos dos fármacos
Núcleo Celular/metabolismo
Células HEK293
Infecções por HIV/virologia
HIV-1/efeitos dos fármacos
Células HeLa
Seres Humanos
Células Jurkat
Espectrometria de Massas
Glicoproteínas de Membrana/química
Proteínas Mutantes/metabolismo
Ligação Proteica/efeitos dos fármacos
Estrutura Secundária de Proteína
Integração Viral/efeitos dos fármacos
beta Carioferinas/metabolismo
Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (KPNB1 protein, human); 0 (Membrane Glycoproteins); 0 (Mutant Proteins); 0 (POM121 protein, human); 0 (beta Karyopherins); 0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170906
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182434


  8 / 1933 MEDLINE  
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[PMID]:28821586
[Au] Autor:Wang J; Kang L; Song D; Liu L; Yang S; Ma L; Guo Z; Ding H; Wang H; Yang B
[Ad] Endereço:Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China.
[Ti] Título:Ku70 Senses HTLV-1 DNA and Modulates HTLV-1 Replication.
[So] Source:J Immunol;199(7):2475-2482, 2017 Oct 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human T lymphotropic virus type 1 (HTLV-1) belongs to the deltaretrovirus family and has been linked to multiple diseases. However, the innate host defense against HTLV-1 is unclear. In this study, we report that the expression of Ku70, a known DNA sensor against DNA viruses, could be induced by HTLV-1 infection in HeLa, PMA-differentiated THP1 cells, primary human monocytes, and human monocyte-derived macrophages. In these cells, the overexpression of Ku70 inhibited the HTLV-1 protein expression, whereas the knockdown of Ku70 promoted the HTLV-1 protein expression. Furthermore, the overexpression of Ku70 enhanced the cellular response to HTLV-1 infection, whereas Ku70 knockdown yielded the opposite effect. Additionally, Ku70 was found to interact with HTLV-1 reverse transcription intermediate ssDNA90. ssDNA90 stimulation induced Ku70 expression and Ku70 promoted ssDNA90-triggered innate immune responses. Finally, HTLV-1 infection enhanced the association between Ku70 and stimulator of IFN genes, suggesting that stimulator of IFN genes was involved in Ku70-mediated host defenses against HTLV-1 infection. Taken together, our findings suggest a new sensor that detects HTLV-1 reverse transcription intermediate and controls HTLV-1 replication. These findings may provide new angles to understand host defenses against HTLV-1 infection and HTLV-1-associated diseases.
[Mh] Termos MeSH primário: DNA Viral
Vírus 1 Linfotrópico T Humano/fisiologia
Autoantígeno Ku/genética
Autoantígeno Ku/metabolismo
Replicação Viral
[Mh] Termos MeSH secundário: Células Cultivadas
Produtos do Gene tax/genética
Células HeLa
Vírus 1 Linfotrópico T Humano/genética
Vírus 1 Linfotrópico T Humano/imunologia
Seres Humanos
Imunidade Inata
Interferons/genética
Interferons/imunologia
Autoantígeno Ku/deficiência
Autoantígeno Ku/imunologia
Macrófagos/virologia
Monócitos/virologia
Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Viral); 0 (Gene Products, tax); 0 (gag Gene Products, Human Immunodeficiency Virus); 0 (p19 protein, Human T-lymphotropic virus 1); 9008-11-1 (Interferons); EC 4.2.99.- (Ku Autoantigen)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170820
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1700111


  9 / 1933 MEDLINE  
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[PMID]:28797020
[Au] Autor:Ngandu NK; Carlson JM; Chopera DR; Ndabambi N; Abdool Karim Q; Abdool Karim S; Williamson C
[Ad] Endereço:*Division of Medical Virology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town and National Health Laboratory Services, Cape Town, South Africa;†Currently, Health Systems Research Unit, South African Medical Research Council, Cape Town, South Africa;‡Microsoft Research, Redmond, WA; and§Centre for the AIDS Programme of Research in South Africa, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
[Ti] Título:Brief Report: Selection of HIV-1 Variants With Higher Transmission Potential by 1% Tenofovir Gel Microbicide.
[So] Source:J Acquir Immune Defic Syndr;76(1):43-47, 2017 Sep 01.
[Is] ISSN:1944-7884
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Women in the CAPRISA 004 trial assigned to use 1% tenofovir (TFV) microbicide gel, who became HIV-1 infected, had higher viral load set-point and slower antibody avidity maturation compared with placebo participants. We investigated whether TFV gel was selected for viruses with altered genetic characteristics. SETTING: The participants of the CAPRISA 004 trial (n = 28 TFV and 43 placebo) were from KwaZulu-Natal Province, South Africa and were infected with HIV-1 subtype C. After HIV-1 diagnosis, they were recruited into the CAPRISA 002 cohort. METHODS: We analyzed gag sequences from the earliest time point post infection (within 3 months of estimated time of infection). Transmission index was measured using a model which predicts the likelihood of an amino acid to be transmitted. Phylogenetic distance from a regional consensus sequence was calculated from a maximum likelihood phylogenetic tree. RESULTS: Transmission index and distance from the most common (consensus) sequence have been shown to be markers of transmission fitness. We found that viruses infecting TFV gel recipients were closer to the consensus sequence of regional strains (P = 0.003) and had higher transmission index (P = 0.01). The transmission index was weakly correlated with concomitant viral load (Spearman r = 0.22, P = 0.06). CONCLUSION: Decreased acquisition risk may have increased the barrier to infection therefore selecting for fitter, more consensus-like viruses. Such virus fitness effects will need to be considered for future pre-exposure prophylaxis and vaccine trials.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/farmacologia
Anti-Infecciosos/farmacologia
Infecções por HIV/transmissão
Infecções por HIV/virologia
HIV-1/efeitos dos fármacos
HIV-1/genética
Tenofovir/uso terapêutico
Cremes, Espumas e Géis Vaginais/uso terapêutico
[Mh] Termos MeSH secundário: Fármacos Anti-HIV/administração & dosagem
Fármacos Anti-HIV/uso terapêutico
Anti-Infecciosos/administração & dosagem
Anti-Infecciosos/uso terapêutico
Ensaios Clínicos como Assunto
Feminino
Infecções por HIV/prevenção & controle
Seres Humanos
Filogenia
Profilaxia Pré-Exposição
Análise de Sequência de DNA
África do Sul/epidemiologia
Resultado do Tratamento
Carga Viral
Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Anti-Infective Agents); 0 (Vaginal Creams, Foams, and Jellies); 0 (gag Gene Products, Human Immunodeficiency Virus); 99YXE507IL (Tenofovir)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE
[do] DOI:10.1097/QAI.0000000000001458


  10 / 1933 MEDLINE  
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[PMID]:28726130
[Au] Autor:Zhang Z; Dai L; Jiang Y; Feng K; Liu L; Xia W; Yu F; Yao J; Xing W; Sun L; Zhang T; Wu H; Su B; Qiu M
[Ad] Endereço:National AIDS Reference Laboratory, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.
[Ti] Título:Transmission network characteristics based on env and gag sequences from MSM during acute HIV-1 infection in Beijing, China.
[So] Source:Arch Virol;162(11):3329-3338, 2017 Nov.
[Is] ISSN:1432-8798
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Molecular epidemiology can be used to identify human immunodeficiency virus (HIV) transmission clusters, usually using pol sequence for analysis. In the present study, we explored appropriate parameters to construct a simple network using HIV env and gag sequences instead of pol sequences for constructing a phylogenetic tree and a genetic transmission subnetwork, which were used to identify individuals with many potential transmission links and to explore the evolutionary dynamics of the virus among men who have sex with men (MSM) in Beijing. We investigated 70 acute HIV-1 infections, which consisted of HIV-1 subtype B (15.71%), the circulating recombinant forms CRF01_AE (47.14%), CRF07_BC (21.43%), CRF55_01B (1.43%), and CRF65_cpx (4.29%), and an unknown subtype (10.00%). By exploring the similarities and differences among HIV env, gag and pol sequences in describing the dynamics of the HIV-1 CRF01_AE transmission subnetwork among Beijing MSM, we found that four key points of the env sequences (strains E-2011_BJ.CY_16014, E-2011_BJ.FT_16017, E-2011_BJ.TZ_16064, and E-2011_BJ.XW_16035) contained more transmission information than gag sequences (three key points: strains G-2011_BJ.CY_16014, G-2011_BJ.FT_16017, and G-2011_BJ.XW_16035) and pol sequences (two key points: strains P-2011_BJ.CY_16014 and P-2011_BJ.XW_16035). Although the env and gag sequence results were similar to pol sequences in describing the dynamics of the HIV-1 CRF01_AE transmission subnetwork, we were able to obtain more precise information, allowing identification of key points of subnetwork expansion, based on HIV env and gag sequences instead of pol sequences. Taken together, the key points we found will improve our current understanding of how HIV spreads between MSM populations in Beijing and help to better target preventative interventions for promoting public health.
[Mh] Termos MeSH primário: Produtos do Gene env/metabolismo
Infecções por HIV/transmissão
Infecções por HIV/virologia
HIV-1/genética
Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo
[Mh] Termos MeSH secundário: Adulto
Pequim/epidemiologia
Regulação Viral da Expressão Gênica
Produtos do Gene env/genética
Infecções por HIV/epidemiologia
Homossexualidade Masculina
Seres Humanos
Masculino
Filogenia
Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gene Products, env); 0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1007/s00705-017-3485-z



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