keyword
MENU ▼
Read by QxMD icon Read
search

HIV mutant

keyword
https://www.readbyqxmd.com/read/28747658/a-single-amino-acid-substitution-confers-b-cell-clonogenic-activity-to-the-hiv-1-matrix-protein-p17
#1
Cinzia Giagulli, Pasqualina D'Ursi, Wangxiao He, Simone Zorzan, Francesca Caccuri, Kristen Varney, Alessandro Orro, Stefania Marsico, Benoît Otjacques, Carlo Laudanna, Luciano Milanesi, Riccardo Dolcetti, Simona Fiorentini, Wuyuan Lu, Arnaldo Caruso
Recent data highlight the presence, in HIV-1-seropositive patients with lymphoma, of p17 variants (vp17s) endowed with B-cell clonogenicity, suggesting a role of vp17s in lymphomagenesis. We investigated the mechanisms responsible for the functional disparity on B cells between a wild-type p17 (refp17) and a vp17 named S75X. Here, we show that a single Arginine (R) to Glycine (G) mutation at position 76 in the refp17 backbone (p17R76G), as in the S75X variant, is per se sufficient to confer a B-cell clonogenic potential to the viral protein and modulate, through activation of the PTEN/PI3K/Akt signaling pathway, different molecules involved in apoptosis inhibition (CASP-9, CASP-7, DFF-45, NPM, YWHAZ, Src, PAX2, MAPK8), cell cycle promotion and cancer progression (CDK1, CDK2, CDK8, CHEK1, CHEK2, GSK-3 beta, NPM, PAK1, PP2C-alpha)...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747495/hiv-and-siv-maintain-high-levels-of-infectivity-in-the-complete-absence-of-mucin-type-o-glycosylation
#2
James M Termini, Elizabeth S Church, Zachary A Silver, Stuart M Haslam, Anne Dell, Ronald C Desrosiers
A highly conserved threonine near the C-terminus of gp120 of HIV and SIV was investigated for its contributions to envelope protein function and virion infectivity. When this highly conserved Thr residue was substituted with anything other than serine (the other amino acid that can accept O-glycosylation), the resulting virus was non-infectious. We found that this Thr was critical for the association of gp120 with the virion and that amino acid substitution increased the amount of dissociated gp120 in the cell culture supernatant...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28743825/contribution-of-the-clathrin-adaptor-ap-1-subunit-%C3%A2%C2%B51-to-acidic-cluster-protein-sorting
#3
Paloma Navarro Negredo, James R Edgar, Antoni G Wrobel, Nathan R Zaccai, Robin Antrobus, David J Owen, Margaret S Robinson
Acidic clusters act as sorting signals for packaging cargo into clathrin-coated vesicles (CCVs), and also facilitate down-regulation of MHC-I by HIV-1 Nef. To find acidic cluster sorting machinery, we performed a gene-trap screen and identified the medium subunit (µ1) of the clathrin adaptor AP-1 as a top hit. In µ1 knockout cells, intracellular CCVs still form, but acidic cluster proteins are depleted, although several other CCV components were either unaffected or increased, indicating that cells can compensate for long-term loss of AP-1...
July 25, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28737946/structure-guided-optimization-of-hiv-integrase-strand-transfer-inhibitors
#4
Xue Zhi Zhao, Steven J Smith, Daniel P Maskell, Mathieu Métifiot, Valerie E Pye, Katherine Fesen, Christophe Marchand, Yves Pommier, Peter Cherepanov, Stephen H Hughes, Terrence R Burke
Integrase mutations can reduce effectiveness of the first-generation FDA-approved integrase strand transfer inhibitors (INSTIs), raltegravir (RAL) and elvitegravir (EVG). The second-generation agent, dolutegravir (DTG) has enjoyed considerable clinical success; however, resistance-causing mutations that diminish the efficacy of DTG have appeared. Our current findings support and extend the substrate envelope concept that broadly effective INSTIs can be designed by filling the envelope defined by the DNA substrates...
July 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28731615/the-prevalence-of-ccr5-%C3%AE-32-mutation-in-a-cohort-of-saudi-stem-cell-donors
#5
M Alarifi, F Al-Amro, A Alalwan, A Al-Turki, H Fakhoury, N Atallah, M Al Muallimi, M Al-Balwi, M ALzahrani, A Alaskar, A Hajeer, D Jawdat
CCR5 is a chemokine receptor that also was found to be used by HIV as a co-receptor for entering target cells. A 32 bp deletion was described in certain people that rendered CCR5 non-functional. The mutant allele CCR5-Δ32 has been shown to prevent HIV infection. In addition, stem cell transplantation with the CCR5-Δ32 homozygous genotype can lead to clearance of HIV infection. In this study, our aim was to investigate the frequency of CCR5-Δ32 mutation in a cohort of stem cell donors from cord blood bank and stem cell donor registry...
July 21, 2017: HLA
https://www.readbyqxmd.com/read/28730622/susceptibility-to-hiv-1-infection-is-influenced-by-toll-like-receptor-2-196-to-174-polymorphism-in-north-indian-population
#6
Sanjukta Vidyant, Animesh Chatterjee, Vikas Agarwal, Tapan N Dhole
INTRODUCTION: Toll like receptors (TLRs) are pattern recognition receptors, recognize molecular patterns of pathogens and play an important role in innate immunity. Recent studies have identified that single nucleotide polymorphism (SNPs) in TLR gene impairs the response to TLR ligands in some individuals and is associated with susceptibility to various infectious diseases. AIM: The aim of the present study is to investigate the role of four SNPs in the TLR2 gene, -196 to -174 Ins/Del, 2258 G/A (Arg753Gln), 2029 C/T (Arg677Trp) and 1892 C/A (Pro631His) with susceptibility and progression to HIV-1 in North Indian individuals...
July 20, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28727807/digoxin-reveals-a-functional-connection-between-hiv-1-integration-preference-and-t-cell-activation
#7
Alexander Zhyvoloup, Anat Melamed, Ian Anderson, Delphine Planas, Chen-Hsuin Lee, Janos Kriston-Vizi, Robin Ketteler, Andy Merritt, Jean-Pierre Routy, Petronela Ancuta, Charles R M Bangham, Ariberto Fassati
HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28699853/foxo4-negatively-controls-tat-mediated-hiv-1-transcription-through-the-post-transcriptional-suppression-of-tat-encoding-mrna
#8
Alexandra Oteiza, Nadir Mechti
The connection between the repression of human immunodeficiency virus type 1(HIV-1) transcription and the resting CD4+ T cell state suggests that the host transcription factors involved in the active maintenance of lymphocyte quiescence are likely to repress the viral transactivator, Tat, thereby restricting HIV-1 transcription. In this study, we analysed the interplay between Tat and the forkhead box transcription factors, FoxO1 and FoxO4. We show that FoxO1 and FoxO4 antagonize Tat-mediated transactivation of HIV-1 promoter through the repression of Tat protein expression...
July 12, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28683086/phosphorylation-of-the-hiv-1-capsid-by-melk-triggers-uncoating-to-promote-viral-cdna-synthesis
#9
Hiroaki Takeuchi, Hideki Saito, Takeshi Noda, Tadashi Miyamoto, Tomokazu Yoshinaga, Kazutaka Terahara, Hiroshi Ishii, Yasuko Tsunetsugu-Yokota, Shoji Yamaoka
Regulation of capsid disassembly is crucial for efficient HIV-1 cDNA synthesis after entry, yet host factors involved in this process remain largely unknown. Here, we employ genetic screening of human T-cells to identify maternal embryonic leucine zipper kinase (MELK) as a host factor required for optimal uncoating of the HIV-1 core to promote viral cDNA synthesis. Depletion of MELK inhibited HIV-1 cDNA synthesis with a concomitant delay of capsid disassembly. MELK phosphorylated Ser-149 of the capsid in the multimerized HIV-1 core, and a mutant virus carrying a phosphorylation-mimetic amino-acid substitution of Ser-149 underwent premature capsid disassembly and earlier HIV-1 cDNA synthesis, and eventually failed to enter the nucleus...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28682562/-renal-diseases-related-to-myh9-disorders
#10
Dario Galeano, Luca Zanoli, Vincenzo L'Imperio, Pasquale Fatuzzo, Antonio Granata
Mutations in MYH9 gene encoding the nonmuscle myosin heavy chain IIA (NMMHC-IIA) are related to a number of rare autosomal-dominant disorders which has been known as May-Hegglin disease, Sebastian syndrome, Fechtner syndrome and Epstein syndrome. Their common clinical features are congenital macrothrombocytopaenia and polymorphonuclear inclusion bodies, in addition to a variable risk of developing proteinuria, chronic kidney disease progressing toward end stage, sensorineural deafness and presenile cataracts...
April 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28674031/the-role-of-sapa-and-yfga-in-susceptibility-to-antibody-mediated-complement-dependent-killing-and-virulence-of-salmonella-enterica-typhimurium
#11
Edna M Ondari, Jennifer N Heath, Elizabeth J Klemm, Gemma Langridge, Lars Barquist, David A Goulding, Simon Clare, Gordon Dougan, Robert A Kingsley, Calman A MacLennan
The ST313 pathovar of S Typhimurium contributes to a high burden of invasive disease among African infants and HIV-infected adults. It is characterized by genome degradation (loss of coding capacity) and has increased resistance to antibody-dependent complement-mediated killing compared with enterocolitis-causing strains of S Typhimurium. Vaccination is an attractive disease-prevention strategy and leading candidates focus on the induction of bactericidal antibodies. Antibody-resistant strains arising through further gene deletion could compromise such a strategy...
July 3, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28670581/mutant-cas9-transcriptional-activator-activates-hiv-1-in-u1-cells-in-the-presence-and-absence-of-ltr-specific-guide-rnas
#12
Veronica Kim, Brian M Mears, Bonita H Powell, Kenneth W Witwer
CRISPR/Cas9 systems have been advanced as promising tools in the HIV eradication armamentarium for sequence-specific disruption or latency reversal. Enthusiasm is balanced by concerns about off-target host genome modification and effects on HIV evolution. In the chronically HIV-1-infected U1 promonocytic latency model, we have confirmed stimulation of HIV-1 production by a mutant Cas9-transcriptional activator and guide RNAs with two guide RNAs apparently more potent than one. However, significant increases were also observed in the absence of guide RNAs...
2017: Matters (Zur)
https://www.readbyqxmd.com/read/28666874/anti-dengue-virus-activity-of-scytovirin-and-evaluation-of-point-mutation-effects-by-molecular-dynamics-and-binding-free-energy-calculations
#13
Andrei Santos Siqueira, Alex Ranieri Jerônimo Lima, Rafael Conceição de Souza, Alberdan Silva Santos, João Lídio da Silva Gonçalves Vianez Júnior, Evonnildo Costa Gonçalves
The absence of a specific treatment against DENV has led to intensive research into developing strategies for curing the infection. One lectin with high antiviral activity is scytovirin, which was isolated from the cyanobacterium Scytonema varium and has proven activity against HIV and Zaire Ebola Virus. To achieve the results presented here, we tested the affinity of full-length scytovirin, SD1 and SD2 separately, and six SD1 mutants for DENV glycoprotein E carbohydrate by Molecular Dynamics (MD) simulations and binding free energy calculations...
June 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28645089/drug-resistance-mechanism-of-l10f-l10f-n88s-and-l90m-mutations-in-crf01_ae-hiv-1-protease-molecular-dynamics-simulations-and-binding-free-energy-calculations
#14
C S Vasavi, Ramasamy Tamizhselvi, Punnagai Munusami
HIV-1 protease plays a crucial role in viral replication and maturation, which makes it one of the most attractive targets for anti-retroviral therapy. The majority of HIV infections in developing countries are due to non-B subtype. Subtype AE is spreading rapidly and infecting huge population worldwide. The mutations in the active site of subtype AE directly impair the interactions with the inhibitor. The non-active site mutations influence the binding of the inhibitor indirectly and their resistance mechanism is not well understood...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28630490/pyroptosis-superinfection-and-the-maintenance-of-the-latent-reservoir-in-hiv-1-infection
#15
Dominik Wodarz, David N Levy
A long-lived reservoir of latently infected T cells prevents antiretroviral therapy from eliminating HIV-1 infection. Furthering our understanding of the dynamics of latency generation and maintenance is therefore vital to improve treatment outcome. Using mathematical models and experiments, we suggest that the death of latently infected cells brought about by pyroptosis, or to a lesser extent by superinfection, might be key mechanisms to account for the size and composition of the latent reservoir. Pyroptosis is a form of cell death that occurs in a resting (and thus latently infected) T cell when a productively infected cell attempts cell-to-cell transmission of virus...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28628334/chiral-indolylarylsulfone-non-nucleoside-reverse-transcriptase-inhibitors-as-new-potent-and-broad-spectrum-anti-hiv-1-agents
#16
Valeria Famiglini, Giuseppe La Regina, Antonio Coluccia, Domiziana Masci, Andrea Brancale, Roger Badia, Eva Riveira-Muñoz, José A Esté, Emmanuele Crespan, Alessandro Brambilla, Giovanni Maga, Myriam Catalano, Cristina Limatola, Francesca Romana Formica, Roberto Cirilli, Ettore Novellino, Romano Silvestri
We designed and synthesized a series of chiral indolyarylsulfones (IASs) as new HIV-1 NNRTIs. The new IASs 8-37 showed potent inhibition of the HIV-1 WT NL4-3 strain and of the mutant K103N, Y181C, Y188L, and K103N-Y181C HIV-1 strains. Six racemic mixtures, 8, 23-25, 31, and 33, were separated at semipreparative level into their pure enantiomers. The (R)-8 enantiomer bearing the chiral (α-methylbenzyl) was superior to the (S)-counterpart. IAS derivatives bearing the (S) alanine unit, (S)-23, (S,R)-25, (S)-31, and (S)-33, were remarkably more potent than the corresponding (R)-enantiomers...
July 5, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28623781/inhibition-activities-of-catechol-diether-based-non-nucleoside-inhibitors-against-the-hiv-reverse-transcriptase-variants-insights-from-molecular-docking-and-oniom-calculations
#17
Pabitra Narayan Samanta, Kalyan Kumar Das
The therapeutic effectiveness of the catechol diether analogs against both the wild-type and drug-resistant reverse transcriptase (RT) mutants of HIV strains are investigated by performing molecular docking and hybrid ONIOM calculations. The docking protocol has been used to predict the binding modes of the non-nucleoside inhibitors inside the active site cavity of the viral enzymes. For each enzyme-inhibitor adduct, the predicted docked poses are assessed by employing different scoring function based programs...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28623359/allosteric-modulatory-effects-of-sri-20041-and-sri-30827-on-cocaine-and-hiv-1-tat-protein-binding-to-human-dopamine-transporter
#18
Wei-Lun Sun, Pamela M Quizon, Yaxia Yuan, Wei Zhang, Subramaniam Ananthan, Chang-Guo Zhan, Jun Zhu
Dopamine transporter (DAT) is the target of cocaine and HIV-1 transactivator of transcription (Tat) protein. Identifying allosteric modulatory molecules with potential attenuation of cocaine and Tat binding to DAT are of great scientific and clinical interest. We demonstrated that tyrosine 470 and 88 act as functional recognition residues in human DAT (hDAT) for Tat-induced inhibition of DA transport and transporter conformational transitions. Here we investigated the allosteric modulatory effects of two allosteric ligands, SRI-20041 and SRI-30827 on cocaine binding on wild type (WT) hDAT, Y470 H and Y88 F mutants...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615206/plasticity-and-epitope-exposure-of-the-hiv-1-envelope-trimer
#19
Rebecca L R Powell, Maxim Totrov, Vincenza Itri, Xiaomei Liu, Alisa Fox, Susan Zolla-Pazner
We recently showed that mutations in the HIV-1 Envelope (Env) destabilize the V3 loop, rendering neutralization-resistant viruses sensitive to V3-directed monoclonal antibodies (mAbs). Here we investigated the propagation of this effect on other Env epitopes, with special emphasis on V2 loop exposure. Wildtype JR-FL and 19 mutant JR-FL pseudoviruses were tested for neutralization sensitivity to 21 mAbs specific for epitopes in V2, the CD4 binding site (CD4bs), and the CD4-induced (CD4i) region. Certain glycan mutants, mutations in the gp120 hydrophobic core, and mutations in residues involved in intra-protomer interactions exposed epitopes in the V2i region (overlays the α4β7 integrin binding site) and the V3 crown, suggesting a general destabilization of the distal region of the trimer apex...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28610923/l368f-v408f-double-mutant-of-ibd-of-ledgf-p75-retains-interaction-with-m178i-mutant-of-hiv-1-integrase
#20
Anu George, Nidhanapati K Raghavendra
Lens-epithelium-derived-growth factor (LEDGF/p75) is an essential host protein for integration of HIV-1 DNA into host genome. Earlier alanine scanning mutational analysis has revealed that residues I365, D366 and F406 in the integrase binding domain (IBD) of p75 are critical for interaction with HIV-1 integrase (IN), while K364, V408 have intermediate effect and residues N367, L368, R405, K407 show wild type binding with IN. To gain insight into contribution of side chains of L368 and V408 that are adjacent to critical residues I365 and F406, respectively, site directed mutation of these residues to Ile/Leu, Met and Phe has been performed and characterized in this study...
August 19, 2017: Biochemical and Biophysical Research Communications
keyword
keyword
98395
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"