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https://www.readbyqxmd.com/read/28726630/dissection-of-specific-binding-of-hiv-1-gag-to-the-packaging-signal-in-viral-rna
#1
Mauricio Comas-Garcia, Siddhartha Ak Datta, Laura Baker, Rajat Varma, Prabhakar R Gudla, Alan Rein
Selective packaging of HIV-1 genomic RNA (gRNA) requires the presence of a cis-acting RNA element called the "packaging signal" (Ψ). However, the mechanism by which Ψ promotes selective packaging of the gRNA is not well understood. We used fluorescence correlation spectroscopy and quenching data to monitor the binding of recombinant HIV-1 Gag protein to Cy5-tagged 190-base RNAs. At physiological ionic strength, Gag binds with very similar, nanomolar affinities to both Ψ-containing and control RNAs. We challenged these interactions by adding excess competing tRNA; introducing mutations in Gag; or raising the ionic strength...
July 20, 2017: ELife
https://www.readbyqxmd.com/read/28726130/transmission-network-characteristics-based-on-env-and-gag-sequences-from-msm-during-acute-hiv-1-infection-in-beijing-china
#2
Zhimin Zhang, Lili Dai, Yan Jiang, Kaidi Feng, Lifeng Liu, Wei Xia, Fengjiao Yu, Jun Yao, Wenge Xing, Lijun Sun, Tong Zhang, Hao Wu, Bin Su, Maofeng Qiu
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...
July 19, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28721397/hivis-dna-or-hivisopt-dna-priming-followed-by-cmdr-vaccinia-based-boosts-induce-both-humoral-and-cellular-murine-immune-responses-to-hiv
#3
J Hinkula, S Petkov, K Ljungberg, D Hallengärd, A Bråve, M Isaguliants, T Falkeborn, S Sharma, V Liakina, M Robb, M Eller, B Moss, G Biberfeld, E Sandström, C Nilsson, K Markland, P Blomberg, B Wahren
BACKGROUND: In order to develop a more effective prophylactic HIV-1 vaccine it is important optimize the components, improve Envelope glycoprotein immunogenicity as well as to explore prime-boost immunization schedules. It is also valuable to include several HIV-1 subtype antigens representing the world-wide epidemic. METHODS: HIVIS-DNA plasmids which include Env genes of subtypes A, B and C together with Gag subtypes A and B and RTmut/Rev of subtype B were modified as follows: the Envelope sequences were shortened, codon optimized, provided with an FT4 sequence and an immunodominant region mutated...
June 2017: Heliyon
https://www.readbyqxmd.com/read/28710431/hiv-1-enhances-mtorc1-activity-and-repositions-lysosomes-to-the-periphery-by-co-opting-rag-gtpases
#4
Alessandro Cinti, Valerie Le Sage, Miroslav P Milev, Fernando Valiente-Echeverría, Christina Crossie, Marie-Joelle Miron, Nelly Panté, Martin Olivier, Andrew J Mouland
HIV-1 co-opts several host machinery to generate a permissive environment for viral replication and transmission. In this work we reveal how HIV-1 impacts the host translation and intracellular vesicular trafficking machineries for protein synthesis and to impede the physiological late endosome/lysosome (LEL) trafficking in stressful conditions. First, HIV-1 enhances the activity of the master regulator of protein synthesis, the mammalian target of rapamycin (mTOR). Second, the virus commandeers mTOR-associated late endosome/lysosome (LEL) trafficking and counteracts metabolic and environmental stress-induced intracellular repositioning of LEL...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701422/new-highly-sensitive-real-time-pcr-assay-for-hiv-2-group-a-and-group-b-dna-quantification
#5
Mélanie Bertine, Marie Gueudin, Adeline Mélard, Florence Damond, Diane Descamps, Sophie Matheron, Fidéline Collin, Christine Rouzioux, Jean-Christophe Plantier, Véronique Avettand-Fenoel
HIV-2 infection is characterized by a very low replication in most cases and low progression. That necessitates a different approach to patient monitoring than that for HIV-1 infection. Here, a new, highly specific, and sensitive method for HIV-2 DNA quantification has been developed. The new test is based on quantitative real-time PCR, targeting the LTR and Gag regions and using an internal control. Analytical performance was determined in three laboratories and clinical performance on blood samples from 63 patients infected with HIV-2 group A (n=35) or group B (n=28)...
July 12, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28701395/preferential-targeting-of-conserved-gag-regions-after-vaccination-with-a-heterologous-dna-prime-modified-vaccinia-ankara-mva-boost-hiv-1-vaccine-regimen
#6
Asli Bauer, Lilli Podola, Philipp Mann, Marco Missanga, Antelmo Haule, Lwitiho Sudi, Charlotta Nilsson, Bahati Kaluwa, Cornelia Lueer, Maria Mwakatima, Patricia J Munseri, Leonard Maboko, Merlin L Robb, Sodsai Tovanabutra, Gustavo Kijak, Mary Marovich, Sheena McCormack, Sarah Joseph, Eligius Lyamuya, Britta Wahren, Eric Sandström, Gunnel Biberfeld, Michael Hoelscher, Muhammad Bakari, Arne Kroidl, Christof Geldmacher
Prime-boost vaccination strategies against HIV-1 often include multiple variants for a given immunogen for better coverage of the extensive viral diversity. To study the immunologic effects of this approach, we characterized breadth, phenotype, function and specificity of Gag-specific T cells induced by a DNA-prime Modified Vaccinia Ankara (MVA)-boost vaccination strategy, which uses mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian volunteers received three injections of the DNA-SMI vaccine encoding for a subtype B and AB-recombinant Gagp37 and two vaccinations with MVA-CMDR encoding subtype A Gagp55 Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28681118/naturally-occurring-vpr-inhibitors-from-medicinal-plants-of-myanmar
#7
REVIEW
Nwet Nwet Win, Hla Ngwe, Ikuro Abe, Hiroyuki Morita
Human immunodeficiency virus type-1 (HIV-1) is a lentiviral family member that encodes the retroviral Gag, Pol, and Env proteins, along with six additional accessory proteins, Tat, Rev, Vpu, Vif, Nef, and Vpr. The currently approved anti-HIV drugs target the Pol and Env encoded proteins. However, these drugs are only effective in reducing viral replication. Furthermore, the drugs' toxicities and the emergence of drug-resistant strains have become serious worldwide problems. Resistance eventually arises to all of the approved anti-HIV drugs, including the newly approved drugs that target HIV integrase (IN)...
July 5, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28677168/impact-of-hla-drb1-allele-polymorphisms-on-control-of-hiv-infection-in-a-peruvian-msm-cohort
#8
B Oriol-Tordera, A Llano, C Ganoza, S Cate, W Hildebrand, J Sanchez, M L Calle, C Brander, A Olvera
Associations between HLA class II polymorphisms and HIV control were assessed in a Peruvian MSM cohort. Among 233 treatment naïve HIV+ individuals, DRB1*13:02 was linked to elevated viral loads (P = .044) while DRB1*12:01 showed significantly lower viral set points (P = .015) and restricted a dominant T cell response to HIV Gag p24 (P = .038). The present work contributes to a better knowledge of the Peruvian immunogenetics and supports the important role of HLA class II restricted T cells in HIV control...
July 5, 2017: HLA
https://www.readbyqxmd.com/read/28673553/hiv-1-sequence-necessary-and-sufficient-to-package-non-viral-rnas-into-hiv-1-particles
#9
Yang Liu, Olga A Nikolaitchik, Sheikh Abdul Rahman, Jianbo Chen, Vinay K Pathak, Wei-Shau Hu
Genome packaging is an essential step to generate infectious HIV-1 virions and is mediated by interactions between the viral protein Gag and cis-acting elements in the full-length RNA. The sequence necessary and sufficient to allow RNA genome packaging into an HIV-1 particle has not been defined. Here, we used two distinct reporter systems to determine the HIV-1 sequence required for heterologous, non-viral RNAs to be packaged into viral particles. Although the 5' untranslated region (UTR) of the HIV-1 RNA is known to be important for RNA packaging, we found that its ability to mediate packaging relies heavily on the context of the downstream sequences...
June 30, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28671952/differences-in-serum-iga-responses-to-hiv-1-gp41-in-elite-controllers-compared-to-viral-suppressors-on-highly-active-antiretroviral-therapy
#10
Rafiq Nabi, Zina Moldoveanu, Qing Wei, Elizabeth T Golub, Helen G Durkin, Ruth M Greenblatt, Betsy C Herold, Marek J Nowicki, Seble Kassaye, Michael W Cho, Abraham Pinter, Alan L Landay, Jiri Mestecky, Pamela A Kozlowski
Mechanisms responsible for natural control of human immunodeficiency type 1 (HIV) replication in elite controllers (EC) remain incompletely defined. To determine if EC generate high quality HIV-specific IgA responses, we used Western blotting to compare the specificities and frequencies of IgA to HIV antigens in serum of gender-, age- and race-matched EC and aviremic controllers (HC) and viremic noncontrollers (HN) on highly active antiretroviral therapy (HAART). Concentrations and avidity of IgA to HIV antigens were measured using ELISA or multiplex assays...
2017: PloS One
https://www.readbyqxmd.com/read/28652475/correction-for-yu-et-al-c-terminal-hiv-1-transframe-p6-tetrapeptide-blocks-enhanced-gag-cleavage-incurred-by-leucine-zipper-replacement-of-a-deleted-p6-domain
#11
Fu-Hsien Yu, Kuo-Jung Huang, Chin-Tien Wang
No abstract text is available yet for this article.
July 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28648546/process-intensification-for-high-yield-production-of-influenza-h1n1-gag-virus-like-particles-using-an-inducible-hek-293-stable-cell-line
#12
Alina Venereo-Sanchez, Melanie Simoneau, Stéphane Lanthier, Parminder Chahal, Lucie Bourget, Sven Ansorge, Rénald Gilbert, Olivier Henry, Amine Kamen
Influenza virus dominant antigens presentation using virus like particle (VLP) approach is attractive for the development of new generation of influenza vaccines. Mammalian cell platform offers many advantages for VLP production. However, limited attention has been paid to the processing of mammalian cell produced VLPs. Better understanding of the production system could contribute to increasing the yields and making large-scale VLP vaccine manufacturing feasible. In a previous study, we have generated a human embryonic kidney HEK-293 inducible cell line expressing Hemagglutinin (HA) and Neuraminidase (NA), which was used to produce VLPs upon transient transfection with a plasmid containing HIV-1 Gag...
June 22, 2017: Vaccine
https://www.readbyqxmd.com/read/28641535/hiv-1-transcription-inhibitors-increase-the-synthesis-of-viral-non-coding-rna-that-contribute-to-latency
#13
Yao A Akpamagbo, Catherine DeMarino, Michelle L Pleet, Angela Schwab, Myosotys Rodriguez, Robert A Barclay, Gavin Sampey, Sergey Iordanskiy, Nazira El-Hage, Fatah Kashanchi
BACKGROUND: HIV-1 can be preserved in long-lived resting CD4+ T- and myeloid cells, forming a viral reservoir in tissues of the infected individuals. Infected patients primarily receive cART, which, to date, is the most efficient treatment against HIV/AIDS. However, the major problem in the eradication of HIV-1 from patients is the lack of therapeutic approaches to recognize the latent HIV-1 provirus and to eliminate latently infected cells. RESULTS: In the current review, we describe the effect of HIV-1 transcriptional inhibitors CR8#13 and F07#13 using a series of in vitro and in vivo assays...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28637761/mother-to-child-hiv-transmission-bottleneck-selects-for-consensus-virus-with-lower-gag-protease-driven-replication-capacity
#14
Vanessa L Naidoo, Jaclyn K Mann, Christie Noble, Emily Adland, Jonathan M Carlson, Jake Thomas, Chanson J Brumme, Christina F Thobakgale-Tshabalala, Zabrina L Brumme, Mark A Brockman, Philip J R Goulder, Thumbi Ndung'u
HIV infection is in the large majority of cases established by a single variant and understanding the characteristics of successfully transmitted variants is relevant to prevention strategies. Few studies have investigated the viral determinants of mother-to-child transmission. To determine the impact of Gag-protease driven viral replication capacity on mother-to-child transmission, the replication capacities of 148 recombinant viruses encoding plasma derived Gag-protease from 53 non-transmitter mothers, 48 transmitter mothers and 47 infected infants were assayed in an HIV-1 inducible green fluorescent protein reporter cell line...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28623276/gag-protease-coevolution-analyses-define-novel-structural-surfaces-in-the-hiv-1-matrix-and-capsid-involved-in-resistance-to-protease-inhibitors
#15
Francisco M Codoñer, Ruth Peña, Oscar Blanch-Lombarte, Esther Jimenez-Moyano, Maria Pino, Thomas Vollbrecht, Bonaventura Clotet, Javier Martinez-Picado, Rika Draenert, Julia G Prado
Despite the major role of Gag in establishing resistance of HIV-1 to protease inhibitors (PIs), very limited data are available on the total contribution of Gag residues to resistance to PIs. To identify in detail Gag residues and structural interfaces associated with the development of HIV-1 resistance to PIs, we traced viral evolution under the pressure of PIs using Gag-protease single genome sequencing and coevolution analysis of protein sequences in 4 patients treated with PIs over a 9-year period. We identified a total of 38 Gag residues correlated with the protease, 32 of which were outside Gag cleavage sites...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28613071/potent-inhibitor-of-drug-resistant-hiv-1-strains-identified-from-the-medicinal-plant-justicia-gendarussa
#16
Hong-Jie Zhang, Emily Rumschlag-Booms, Yi-Fu Guan, Dong-Ying Wang, Kang-Lun Liu, Wan-Fei Li, Van H Nguyen, Nguyen M Cuong, Djaja D Soejarto, Harry H S Fong, Lijun Rong
Justicia gendarussa, a medicinal plant collected in Vietnam, was identified as a potent anti-HIV-1 active lead from the evaluation of over 4500 plant extracts. Bioassay-guided separation of the extracts of the stems and roots of this plant led to the isolation of an anti-HIV arylnaphthalene lignan (ANL) glycoside, patentiflorin A (1). Evaluation of the compound against both the M- and T-tropic HIV-1 isolates showed it to possess a significantly higher inhibition effect than the clinically used anti-HIV drug AZT...
June 14, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28611493/construction-selection-and-immunogenicity-of-recombinant-fowlpox-candidate-vaccine-co-expressing-hiv-1-gag-and-gp145
#17
Yilong Zhu, Yan Guo, Shouwen Du, Cunxia Liu, Maopeng Wang, Dayong Ren, Fei Zhao, Yanfang Zhang, Wenchao Sun, Yiquan Li, Tingting Cao, Yingyue Jiang, Bin Xing, Bing Bai, Chang Li, Ningyi Jin
An HIV candidate vaccine for the Chinese population was designed by constructing a recombinant fowlpox virus expressing HIV-1 gag and HIV gp145 proteins via homologous recombination and plaque screening using enhanced green fluorescent protein (EGFP) as the reporter gene. EGFP in the recombinant was then knocked out with the Cre/Loxp system yielding rFPVHg-Hp, which was identified at the genomic, transcriptional and translational levels. The immunogenicity of rFPVHg-Hp was analyzed by measuring levels of HIV-specific antibodies and IFN-γ-secreting splenocytes by enzyme-linked immunosorbent assay and IFN enzyme-linked immune spot test in the BALB/c mouse model...
June 2017: Indian Journal of Microbiology
https://www.readbyqxmd.com/read/28604502/the-association-of-hiv-1-gag-specific-igg-antibodies-with-natural-control-of-hiv-1-infection-in-individuals-not-carrying-hla-b-57-01-is-only-observed-in-viremic-controllers
#18
M Christian Tjiam, Mazmah A Morshidi, Lucy Sariputra, Jeffrey N Martin, Steven G Deeks, Dino Tan, Silvia Lee, Sonia Fernandez, Martyn A French
To expand upon our previous observation that HIV-1 Gag-specific IgG antibodies were highest in HIV controllers not carrying HLA-B*57:01, we analysed these antibodies in a larger cohort of viremic controllers (VCs) or elite controllers (ECs) considering carriage of 'protective' HLA-B alleles. HIV-1 p24-specific IgG1 and IgG2 antibodies were higher only in HLA-B*57:01 VCs but there were no differences in ECs. Associations of HIV-1 gp140-specific IgG antibodies with HLA-B*57:01 carriage were inconsistent amongst VCs and ECs...
June 9, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28602196/sequence-specific-recognition-of-hiv-1-dsdna-in-the-large-amount-of-normal-dsdna-based-upon-nicking-enzyme-signal-amplification-and-triplex-dna
#19
Houya Zhu, Manjun Zhang, Li Zou, Ruimin Li, Liansheng Ling
A sensitive fluorescent strategy for sequence specific recognition of HIV dsDNA was established based upon Nicking Enzyme Signal Amplification (NESA) and triplex formation. dsDNA sequence from the site 7960 to site 7991 of the HIV1 dsDNA gene was designed as target dsDNA, which was composed of two complementary strands Oligonucleotide 1 with the sequence of 3'-CTT CCT TAT CTT CTT CTT CCA CCT CTC TCT CT-5' (Oligo-1) and Oligonucleotide 2 with the sequence of 5'-GAA GGA ATA GAA GAA GAA GGT GGA GAG AGA GA-3' (Oligo-2)...
October 1, 2017: Talanta
https://www.readbyqxmd.com/read/28600226/screening-for-small-molecule-inhibitors-of-hiv-1-gag-expression
#20
Ahalya Balachandran, Alan Cochrane
The control of RNA processing plays an important role in the nature and quantity of protein generated from mammalian genes. Consequently, efforts to manipulate RNA processing have the capacity to significantly impact gene function. Although multiple strategies have been developed to alter splice site selection using oligonucleotide occlusion of splice sites or splicing regulatory elements, systemic delivery of such agents remains problematic. Outlined in this chapter is a protocol to screen for small molecule inhibitors of HIV-1 Gag expression that have been subsequently determined to modulate viral RNA processing...
June 17, 2017: Methods: a Companion to Methods in Enzymology
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