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[PMID]:29338056
[Au] Autor:Tien C; Huang L; Watanabe SM; Speidel JT; Carter CA; Chen C
[Ad] Endereço:Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado, United States of America.
[Ti] Título:Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors.
[So] Source:PLoS One;13(1):e0191372, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:HIV-1 protease autoprocessing is responsible for liberation of free mature protease (PR) from the Gag-Pol polyprotein precursor. A cell-based model system was previously developed to examine the autoprocessing mechanism of fusion precursors carrying the p6*-PR miniprecursor sandwiched between various proteins or epitopes. We here report that precursor autoprocessing is context-dependent as its activity and outcomes can be modulated by sequences upstream of p6*-PR. This was exemplified by the 26aa maltose binding protein (MBP) signal peptide (SigP) when placed at the N-terminus of a fusion precursor. The mature PRs released from SigP-carrying precursors are resistant to self-degradation whereas those released from SigP-lacking fusion precursors are prone to self-degradation. A H69D mutation in PR abolished autoprocessing of SigP-containing fusion precursors whereas it only partially suppressed autoprocessing of fusion precursors lacking SigP. An autoprocessing deficient GFP fusion precursor with SigP exhibited a subcellular distribution pattern distinct from the one without it in transfected HeLa cells. Furthermore, a SigP fusion precursor carrying a substitution at the P1 position released the mature PR and PR-containing fragments that were different from those released from the precursor carrying the same mutation but lacking SigP. We also examined autoprocessing outcomes in viral particles produced by a NL4-3 derived proviral construct and demonstrated the existence of several PR-containing fragments along with the mature PR. Some of these resembled the SigP precursor autoprocessing outcomes. This finding of context-dependent modulation reveals the complexity of precursor autoprocessing regulation that most likely accompanies sequence variation imposed by the evolution of the upstream Gag moiety.
[Mh] Termos MeSH primário: Precursores Enzimáticos/metabolismo
Protease de HIV/metabolismo
HIV-1/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Precursores Enzimáticos/química
Precursores Enzimáticos/genética
Células HEK293
Protease de HIV/química
Protease de HIV/genética
Seres Humanos
Mutação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Enzyme Precursors); EC 3.4.23.- (HIV Protease); EC 3.4.23.- (p16 protease, Human immunodeficiency virus 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191372


  2 / 3323 MEDLINE  
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[PMID]:29023464
[Au] Autor:McGrath CJ; Garcia R; Trinh TT; Richardson BA; John-Stewart GC; Nyongesa-Malava E; Mugo NR; Glynn EH; Sakr SR; De Vuyst H; Chung MH
[Ad] Endereço:Department of Global Health, University of Washington, Seattle, Washington United States of America.
[Ti] Título:Role of p16 testing in cervical cancer screening among HIV-infected women.
[So] Source:PLoS One;12(10):e0185597, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: p16 immunohistochemistry is used to evaluate for HPV-associated cervical intraepithelial neoplasia. The diagnostic performance of p16 in HIV infection is unclear. METHODS: Between June-December 2009, HIV-infected women underwent Papanicolaou (Pap) smear, human papillomavirus (HPV) testing, visual inspection with acetic acid (VIA), and colposcopy-directed biopsy as the disease gold standard at a HIV clinic in Kenya. Pap smears were evaluated for p16 expression. Sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC) of p16 to detect CIN2/3 on histology and the impact of immunosuppression and ART was assessed. RESULTS: Of 331 cervical samples with p16 expression, p16 sensitivity and specificity to detect CIN2/3 was 54.1% and 72.4% respectively, which was lower than Pap and HPV in sensitivity, but higher in specificity than Pap, HPV, and VIA. Combining tests and p16 reduced sensitivity and increased specificity of Pap from 90.5% to 48.7% and 51.4% to 81.7%; of VIA from 59.5% to 37.8% and 67.6% to 89.9%; and of HPV from 82.4% to 50.0% and 55.3% to 84.8%. Combination p16 increased the PPV of Pap from 34.9% to 43.4%; of HPV from 34.7% to 48.7%; and VIA from 34.9% to 51.9%. Adjunctive p16 did not change AUC (P>0.05). P16 performance was not altered by immunosuppression or ART use. Combining p16 with HPV and VIA reduced the variation in HPV and VIA performance associated with CD4 and ART. CONCLUSION: As an adjunctive test in HIV-infected women, p16 immunohistochemistry increased specificity and PPV of HPV and VIA for CIN2/3, and was not altered in performance by immunosuppression, ART, or age.
[Mh] Termos MeSH primário: Infecções por HIV/diagnóstico
Protease de HIV/metabolismo
HIV-1
Neoplasias do Colo do Útero/diagnóstico
Neoplasias do Colo do Útero/epidemiologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Feminino
Infecções por HIV/metabolismo
Infecções por HIV/patologia
Seres Humanos
Imuno-Histoquímica/métodos
Quênia
Programas de Rastreamento/métodos
Meia-Idade
Teste de Papanicolaou/métodos
Neoplasias do Colo do Útero/metabolismo
Neoplasias do Colo do Útero/patologia
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.4.23.- (HIV Protease); EC 3.4.23.- (p16 protease, Human immunodeficiency virus 1)
[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.0185597


  3 / 3323 MEDLINE  
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[PMID]:28872858
[Au] Autor:Huang J; Sun B; Yao Y; Liu J
[Ad] Endereço:School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology , 13 Hangkong Road, Wuhan, Hubei 430030, P.R. China.
[Ti] Título:Fast and Reliable Thermodynamic Approach for Determining the Protonation State of the Asp Dyad.
[So] Source:J Chem Inf Model;57(9):2273-2280, 2017 Sep 25.
[Is] ISSN:1549-960X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The protonation state of the asp dyad is significantly important in revealing enzymatic mechanisms and developing drugs. However, it is hard to determine by calculating free energy changes between possible protonation states, because the free energy changes due to protein conformational flexibility are usually much larger than those originating from different locations of protons. Sophisticated and computationally expensive methods such as free energy perturbation, thermodynamic integration (TI), and quantum mechanics/molecular mechanics are therefore usually used for this purpose. In the present study, we have developed a simple thermodynamic approach to effectively eliminating the free energy changes arising from protein conformational flexibility and estimating the free energy changes only originated from the locations of protons, which provides a fast and reliable method for determining the protonation state of asp dyads. The test of this approach on a total of 15 asp dyad systems, including BACE-1 and HIV-1 protease, shows that the predictions from this approach are all consistent with experiments or with the computationally expensive TI calculations. It is clear that our thermodynamic approach could be used to rapidly and reliably determine the protonation state of the asp dyad.
[Mh] Termos MeSH primário: Ácido Aspártico Endopeptidases/química
Ácido Aspártico
Protease de HIV/química
Prótons
Teoria Quântica
[Mh] Termos MeSH secundário: Ácido Aspártico Endopeptidases/metabolismo
Protease de HIV/metabolismo
Conformação Proteica
Termodinâmica
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protons); 30KYC7MIAI (Aspartic Acid); EC 3.4.23.- (Aspartic Acid Endopeptidases); EC 3.4.23.- (HIV Protease)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170906
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jcim.7b00207


  4 / 3323 MEDLINE  
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[PMID]:28865281
[Au] Autor:Subbaiah MAM; Meanwell NA; Kadow JF
[Ad] Endereço:Prodrug Group, Department of Medicinal Chemistry, Biocon Bristol-Myers Squibb R&D Centre, Biocon Park, Bommasandra Phase IV, Jigani Link Road, Bangalore 560009, India. Electronic address: murugaiah.andappan@syngeneintl.com.
[Ti] Título:Design strategies in the prodrugs of HIV-1 protease inhibitors to improve the pharmaceutical properties.
[So] Source:Eur J Med Chem;139:865-883, 2017 Oct 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Combination antiretroviral therapy (cART) is currently the most effective treatment for HIV-1 infection. HIV-1 protease inhibitors (PIs) are an important component of some regimens of cART. However, PIs are known for sub-optimal ADME properties, resulting in poor oral bioavailability. This often necessitates high drug doses, combination with pharmacokinetic enhancers and/or special formulations in order to effectively deliver PIs, which may lead to a high pill burden and reduced patient compliance. As a remedy, improving the ADME properties of existing drugs via prodrug and other approaches has been pursued in addition to the development of next generation PIs with improved pharmacokinetic, resistance and side effect profiles. Phosphate prodrugs have been explored to address the solubility-limiting absorption and high excipient load. Prodrug design to target carrier-mediated drug delivery has also been explored. Amino acid prodrugs have been shown to improve permeability by engaging active transport mechanisms, reduce efflux and mitigate first pass metabolism while acyl migration prodrugs have been shown to improve solubility. Prodrug design efforts have led to the identification of one marketed agent, fosamprenavir, and clinical studies with two other prodrugs. Several of the reported approaches lack detailed in vivo characterization and hence the potential preclinical or clinical benefits of these approaches are yet to be fully determined.
[Mh] Termos MeSH primário: Desenho de Drogas
Infecções por HIV/tratamento farmacológico
Protease de HIV/metabolismo
Pró-Fármacos/farmacologia
Inibidores de Proteases/farmacologia
[Mh] Termos MeSH secundário: Relação Dose-Resposta a Droga
HIV-1/metabolismo
Estrutura Molecular
Pró-Fármacos/síntese química
Pró-Fármacos/química
Inibidores de Proteases/síntese química
Inibidores de Proteases/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Prodrugs); 0 (Protease Inhibitors); EC 3.4.23.- (HIV Protease); EC 3.4.23.- (p16 protease, Human immunodeficiency virus 1)
[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:170903
[St] Status:MEDLINE


  5 / 3323 MEDLINE  
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[PMID]:28817602
[Au] Autor:Regad L; Chéron JB; Triki D; Senac C; Flatters D; Camproux AC
[Ad] Endereço:Molécules thérapeutiques in silico (MTi), INSERM UMR-S973, Paris, France.
[Ti] Título:Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.
[So] Source:PLoS One;12(8):e0182972, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC), obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at http://www.mti.univ-paris-diderot.fr/recherche/plateformes/logiciels.
[Mh] Termos MeSH primário: Análise de Sequência de Proteína/métodos
Software
[Mh] Termos MeSH secundário: Animais
Domínio Catalítico
Protease de HIV/química
Protease de HIV/metabolismo
Seres Humanos
Ativadores de Plasminogênio/química
Ativadores de Plasminogênio/metabolismo
Ligação Proteica
Conformação Proteica
Proteína Supressora de Tumor p53/química
Proteína Supressora de Tumor p53/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tumor Suppressor Protein p53); EC 3.4.21.- (Plasminogen Activators); EC 3.4.23.- (HIV Protease)
[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:170818
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182972


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[PMID]:28791894
[Au] Autor:Weber IT; Harrison RW
[Ad] Endereço:Department of Biology, Georgia State University, PO Box 4010, Atlanta, GA 30302-4010, USA.
[Ti] Título:Decoding HIV resistance: from genotype to therapy.
[So] Source:Future Med Chem;9(13):1529-1538, 2017 Sep.
[Is] ISSN:1756-8927
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Genetic variation in HIV poses a major challenge for prevention and treatment of the AIDS pandemic. Resistance occurs by mutations in the target proteins that lower affinity for the drug or alter the protein dynamics, thereby enabling viral replication in the presence of the drug. Due to the prevalence of drug-resistant strains, monitoring the genotype of the infecting virus is recommended. Computational approaches for predicting resistance from genotype data and guiding therapy are discussed. Many prediction methods rely on rules derived from known resistance-associated mutations, however, statistical or machine learning can improve the classification accuracy and assess unknown mutations. Adding classifiers such as information on the atomic structure of the protein can further enhance the predictions.
[Mh] Termos MeSH primário: Farmacorresistência Viral/genética
HIV-1/genética
[Mh] Termos MeSH secundário: Antirretrovirais/uso terapêutico
Sítios de Ligação
Genótipo
Infecções por HIV/tratamento farmacológico
Infecções por HIV/genética
Integrase de HIV/química
Integrase de HIV/metabolismo
Protease de HIV/química
Protease de HIV/metabolismo
Transcriptase Reversa do HIV/antagonistas & inibidores
Transcriptase Reversa do HIV/metabolismo
Seres Humanos
Simulação de Dinâmica Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Retroviral Agents); EC 2.7.7.- (HIV Integrase); EC 2.7.7.49 (HIV Reverse Transcriptase); EC 3.4.23.- (HIV Protease)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171126
[Lr] Data última revisão:
171126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE
[do] DOI:10.4155/fmc-2017-0048


  7 / 3323 MEDLINE  
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[PMID]:28739156
[Au] Autor:Funicello M; Chiummiento L; Tramutola F; Armentano MF; Bisaccia F; Miglionico R; Milella L; Benedetti F; Berti F; Lupattelli P
[Ad] Endereço:Dipartimento di Scienze, Università della Basilicata, Via Ateneo Lucano 10, 85100 Potenza, Italy.
[Ti] Título:Synthesis and biological evaluation in vitro and in mammalian cells of new heteroaryl carboxyamides as HIV-protease inhibitors.
[So] Source:Bioorg Med Chem;25(17):4715-4722, 2017 Sep 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:New heteroaryl HIV-protease inhibitors bearing a carboxyamide spacer were synthesized in few steps and high yield, from commercially available homochiral epoxides. Different substitution patterns were introduced onto a given isopropanoyl-sulfonamide core modifying the type of heteroarene and the central core, with the presence of either H or benzyl group. Their in vitro inhibition activity against recombinant protease showed a general beneficial effect of carboxyamide moiety, the IC values ranging between 1 and 15nM. In particular benzofuryl derivatives showed IC values among the best for such structurally simple inhibitors. Docking analysis allowed to identify the favorable situation of such benzofuryl derivatives in terms of number of interactions in the active site, supporting the experimental results on activity. The inhibition activity of such molecules has been also evaluated in HEK293 cells expressing the protease fused to green fluorescent protein, by western blotting analysis, fluorescence microscopy and cytofluorimetry.
[Mh] Termos MeSH primário: Amidas/química
Inibidores da Protease de HIV/síntese química
Protease de HIV/metabolismo
[Mh] Termos MeSH secundário: Amidas/síntese química
Amidas/farmacologia
Sítios de Ligação
Sobrevivência Celular/efeitos dos fármacos
Células HEK293
HIV/efeitos dos fármacos
HIV/enzimologia
Protease de HIV/química
Inibidores da Protease de HIV/farmacologia
Seres Humanos
Concentração Inibidora 50
Microscopia de Fluorescência
Simulação de Acoplamento Molecular
Estrutura Terciária de Proteína
Relação Estrutura-Atividade
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (HIV Protease Inhibitors); EC 3.4.23.- (HIV Protease)
[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:170726
[St] Status:MEDLINE


  8 / 3323 MEDLINE  
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[PMID]:28687227
[Au] Autor:Kent S
[Ad] Endereço:Department of Chemistry, University of Chicago, Chicago, IL 60637, USA. Electronic address: skent@uchicago.edu.
[Ti] Título:Chemical protein synthesis: Inventing synthetic methods to decipher how proteins work.
[So] Source:Bioorg Med Chem;25(18):4926-4937, 2017 Sep 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Total chemical synthesis of proteins has been rendered practical by the chemical ligation principle: chemoselective condensation of unprotected peptide segments equipped with unique, mutually reactive functional groups, enabled by formation of a non-native replacement for the peptide bond. Ligation chemistries are briefly described, including native chemical ligation - thioester-mediated, amide-forming reaction at Xaa-Cys sites - and its extensions. Case studies from the author's own works are used to illustrate the utility and applications of chemical protein synthesis. Selected recent developments in the field are briefly discussed.
[Mh] Termos MeSH primário: Peptídeos/síntese química
Proteínas/síntese química
[Mh] Termos MeSH secundário: Eritropoetina/síntese química
Eritropoetina/química
Eritropoetina/metabolismo
Protease de HIV/síntese química
Protease de HIV/química
Seres Humanos
Insulina/síntese química
Insulina/química
Insulina/metabolismo
Muramidase/síntese química
Muramidase/química
Muramidase/metabolismo
Peptídeos/química
Peptídeos/metabolismo
Dobramento de Proteína
Proteínas/química
Proteínas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Insulin); 0 (Peptides); 0 (Proteins); 11096-26-7 (Erythropoietin); EC 3.2.1.17 (Muramidase); EC 3.4.23.- (HIV Protease); EC 3.4.23.- (p16 protease, Human immunodeficiency virus 1)
[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:170709
[St] Status:MEDLINE


  9 / 3323 MEDLINE  
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[PMID]:28628632
[Au] Autor:Sampath R; Cummins NW; Natesampillai S; Bren GD; Chung TD; Baker J; Henry K; Pagliuzza A; Badley AD
[Ad] Endereço:Division of Infectious Disease, Mayo Clinic Rochester, Rochester, MN, United States of America.
[Ti] Título:Increasing procaspase 8 expression using repurposed drugs to induce HIV infected cell death in ex vivo patient cells.
[So] Source:PLoS One;12(6):e0179327, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:HIV persists because a reservoir of latently infected CD4 T cells do not express viral proteins and are indistinguishable from uninfected cells. One approach to HIV cure suggests that reactivating HIV will activate cytotoxic pathways; yet when tested in vivo, reactivating cells do not die sufficiently to reduce cell-associated HIV DNA levels. We recently showed that following reactivation from latency, HIV infected cells generate the HIV specific cytotoxic protein Casp8p41 which is produced by HIV protease cleaving procaspase 8. However, cell death is prevented, possibly due to low procaspase 8 expression. Here, we tested whether increasing procaspase 8 levels in CD4 T cells will produce more Casp8p41 following HIV reactivation, causing more reactivated cells to die. Screening 1277 FDA approved drugs identified 168 that increased procaspase 8 expression by at least 1.7-fold. Of these 30 were tested for anti-HIV effects in an acute HIVIIIb infection model, and 9 drugs at physiologic relevant levels significantly reduced cell-associated HIV DNA. Primary CD4 T cells from ART suppressed HIV patients were treated with one of these 9 drugs and reactivated with αCD3/αCD28. Four drugs significantly increased Casp8p41 levels following HIV reactivation, and decreased total cell associated HIV DNA levels (flurbiprofen: p = 0.014; doxycycline: p = 0.044; indomethacin: p = 0.025; bezafibrate: P = 0.018) without effecting the viability of uninfected cells. Thus procaspase 8 levels can be increased pharmacologically and, in the context of HIV reactivation, increase Casp8p41 causing death of reactivating cells and decreased HIV DNA levels. Future studies will be required to define the clinical utility of this or similar approaches.
[Mh] Termos MeSH primário: Antirretrovirais/farmacologia
Apoptose/efeitos dos fármacos
Caspase 8/metabolismo
HIV-1/fisiologia
Regulação para Cima/efeitos dos fármacos
[Mh] Termos MeSH secundário: Linfócitos T CD4-Positivos/citologia
Linfócitos T CD4-Positivos/metabolismo
Linfócitos T CD4-Positivos/virologia
Caspase 8/genética
Células Cultivadas
Genes Reporter
Protease de HIV/metabolismo
HIV-1/enzimologia
HIV-1/genética
Seres Humanos
Regiões Promotoras Genéticas
Precursores de Proteínas/genética
Precursores de Proteínas/metabolismo
RNA Viral/metabolismo
Ativação Viral/efeitos dos fármacos
Latência Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Retroviral Agents); 0 (Protein Precursors); 0 (RNA, Viral); EC 3.4.22.- (Caspase 8); EC 3.4.23.- (HIV Protease)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179327


  10 / 3323 MEDLINE  
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[PMID]:28622345
[Au] Autor:Zeng P; Liu Y; He M; Wang J; Keating S; Mao W; Huang M; Ma H; He W; Bi X; Liao D; Busch M; Ness P; Liu J; Shan H; NHLBI Recipient Epidemiology and Donor Evaluation Study-III program
[Ad] Endereço:West China School of Public Health, Sichuan University, Chengdu, Sichuan, China.
[Ti] Título:The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014.
[So] Source:PLoS One;12(6):e0179328, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The increasing complexity and diversity of the human immunodeficiency virus-1 (HIV-1) infections challenge the disease control and anti-retrovirus treatment in China. The infection stages and molecular characteristics of HIV-1 from infected Chinese blood donors were examined to shed light on the HIV genotype distribution and the status of drug resistance mutations (DRMs) in the changing HIV epidemic in China. Western blot (WB) confirmed HIV-1 positive plasma samples were collected from blood donors at five Chinese blood centers from April 16, 2012, through June 30, 2014. The HIV infection stages were determined using the Lag-avidity assay. HIV Pol regions including whole protease and partial reverse transcriptase (RT) were amplified and sequenced to establish the profile of genotype distribution and drug resistance mutations (DRMs). Viral loads were determined using the ROCHE COBAS system. Of the 259 HIV-1 positive samples tested by the Lag-avidity assay, 23.6% (61/259) were identified as recent infections. A total of 205 amplified sequences displayed the following genotype distributions: circulating recombinant form (CRF) 07_BC (61.5%), CRF08_BC (8.3%), CRF01_AE (20%), B (6.3%), and 01B (3.9%). There was no significant difference in genotype distribution between recent and long-term infections. 31 DRMs were identified from 27 samples including four protease inhibitors (PIs) accessory DRMs, two PIs major DRMs (M46I), two nucleoside RT inhibitors DRMs (K219R and K70Q), and 23 nonnucleoside RT inhibitors DRMs. 27 samples had DRMs, yielding a drug resistance prevalence of 13.2% (27/205). Our findings provide important information for developing strategies for comprehensive HIV control and improving anti-retroviral treatment in China.
[Mh] Termos MeSH primário: Bancos de Sangue
Doadores de Sangue
Farmacorresistência Viral/genética
Genótipo
Infecções por HIV/genética
Protease de HIV/genética
Transcriptase Reversa do HIV/genética
HIV-1/genética
Mutação
[Mh] Termos MeSH secundário: Adolescente
Adulto
Grupo com Ancestrais do Continente Asiático
China/epidemiologia
Feminino
Infecções por HIV/tratamento farmacológico
Infecções por HIV/epidemiologia
Inibidores da Protease de HIV/administração & dosagem
Seres Humanos
Masculino
Meia-Idade
Inibidores da Transcriptase Reversa/administração & dosagem
Carga Viral/métodos
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (HIV Protease Inhibitors); 0 (Reverse Transcriptase Inhibitors); EC 2.7.7.- (reverse transcriptase, Human immunodeficiency virus 1); EC 2.7.7.49 (HIV Reverse Transcriptase); EC 3.4.23.- (HIV Protease)
[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:170617
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179328



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