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https://www.readbyqxmd.com/read/28926408/serum-glycan-binding-igg-antibodies-in-hiv-1-infection-and-during-the-development-of-broadly-neutralizing-responses
#1
Cathrine Scheepers, Sudipa Chowdhury, W Shea Wright, Christopher T Campbell, Nigel J Garrett, Quarraisha Abdool Karim, Salim S Abdool Karim, Penny L Moore, Jeffrey C Gildersleeve, Lynn Morris
BACKGROUND: The HIV-1 envelope is covered with glycans that provide structural integrity and protect conserved regions from host antibody responses. However, these glycans are often the target of broadly neutralizing antibodies (bNAbs) that emerge in some HIV infected individuals. We aimed to determine whether anti-glycan IgG antibodies are a general response to HIV-1 infection or specific to individuals who develop bNAbs. METHODS: IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids and Tn-peptides...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28919433/the-p2x7-receptor-in-dorsal-root-ganglia-is-involved-in-hiv-gp120-associated-neuropathic-pain
#2
Bing Wu, Lichao Peng, Jinyan Xie, Lifang Zou, Qicheng Zhu, Huaide Jiang, Zhihua Yi, Shouyu Wang, Yun Xue, Yun Gao, Guilin Li, Shuangmei Liu, Chunping Zhang, Guodong Li, Shangdong Liang, Huangui Xiong
Human immunodeficiency virus (HIV)-associated neuropathic pain is common, and studies have shown that HIV envelope glycoprotein 120 (gp120) can directly stimulate primary sensory afferent neurons causing hyperalgesia. The P2X7 receptor in the dorsal root ganglia (DRG) is involved in pain transmission and is closely related to the inflammatory and immune response. In this study, we aimed to explore the role of the P2X7 receptor in gp120-induced neuropathic pain using a rat model specific for this type of pain...
September 14, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28918303/decoding-noises-in-hiv-computational-genotyping
#3
MingRui Jia, Timothy Shaw, Xing Zhang, Dong Liu, Ye Shen, Amara E Ezeamama, Chunfu Yang, Ming Zhang
Lack of a consistent and reliable genotyping system can critically impede HIV genomic research on pathogenesis, fitness, virulence, drug resistance, and genomic-based healthcare and treatment. At present, mis-genotyping, i.e., background noises in molecular genotyping, and its impact on epidemic surveillance is unknown. For the first time, we present a comprehensive assessment of HIV genotyping quality. HIV sequence data were retrieved from worldwide published records, and subjected to a systematic genotyping assessment pipeline...
September 14, 2017: Virology
https://www.readbyqxmd.com/read/28918033/six-highly-conserved-targets-of-rnai-revealed-in-hiv-1-infected-patients-from-russia-are-also-present-in-many-hiv-1-strains-worldwide
#4
Olga V Kretova, Daria M Fedoseeva, Maria A Gorbacheva, Natalya M Gashnikova, Maria P Gashnikova, Nataliya V Melnikova, Vladimir R Chechetkin, Yuri V Kravatsky, Nickolai A Tchurikov
RNAi has been suggested for use in gene therapy of HIV/AIDS, but the main problem is that HIV-1 is highly variable and could escape attack from the small interfering RNAs (siRNAs) due to even single nucleotide substitutions in the potential targets. To exhaustively check the variability in selected RNA targets of HIV-1, we used ultra-deep sequencing of six regions of HIV-1 from the plasma of two independent cohorts of patients from Russia. Six RNAi targets were found that are invariable in 82%-97% of viruses in both cohorts and are located inside the domains specifying reverse transcriptase (RT), integrase, vpu, gp120, and p17...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28903577/a-2-4-amino-acid-deletion-in-the-v5-region-of-hiv-1-env-gp120-confers-viral-resistance-to-the-broadly-neutralizing-human-monoclonal-antibody-vrc01
#5
Shingo Tachibana, Maho Sasaki, Takako Tanaka, Mari Inoue, Youdiil Ophinni, Tomohiro Kotaki, Masanori Kameoka
The envelope glycoprotein (Env) gp120 of human immunodeficiency virus type 1 (HIV-1) plays a critical role in viral entry into host cells. The broadly neutralizing human monoclonal antibody VRC01, which recognizes the CD4 binding site on gp120, neutralizes more than 90% of HIV-1 isolates. However, some of the CRF01_AE viruses prevalent in Southeast Asia are resistant to VRC01-mediated neutralization. We previously reported that 3 amino acid residues at positions 185, 186, and 197 of gp120 played an important role in the VRC01 resistance of CRF01_AE Env (AE-Env) clones isolated from HIV-infected Thai individuals...
September 13, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28886715/peroxisome-proliferator-activated-receptor-gamma-potential-molecular-therapeutic-target-for-hiv-1-associated-brain-inflammation
#6
Amila Omeragic, Md Tozammel Hoque, U-Yeong Choi, Reina Bendayan
BACKGROUND: Despite the use of combination antiretroviral therapy for the treatment of HIV-1 infection, cognitive impairments remain prevalent due to persistent viral replication and associated brain inflammation. Primary cellular targets of HIV-1 in the brain are macrophages, microglia, and to a certain extent astrocytes which in response to infection release inflammatory markers, viral proteins [i.e., glycoprotein 120 (gp120)] and exhibit impaired glutamate uptake. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily of ligand-activated transcription factors...
September 8, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28851629/immunogenicity-of-virus-like-semliki-forest-virus-replicon-particles-expressing-indian-hiv-1c-gag-env-and-polrt-genes
#7
Seema P Ajbani, Shilpa M Velhal, Ravindra B Kadam, Vainav V Patel, Kenneth Lundstrom, Atmaram H Bandivdekar
Development of a vaccine targeting human immunodeficiency virus-1 subtype C (HIV-1C) is an important public health priority in regions with a high prevalence of the clade C virus. The present study demonstrates the immunogenicity of recombinant Semliki Forest virus (SFV)-based virus-like replicon particles (VRPs) expressing Indian HIV-1C env/gag/polRT genes. Immunization of mice with recombinant VRPs in a homologous prime-boost protocol, either individually or in combination, elicited significant antigen-specific IFN-γ T cell responses as detected by the ELISPOT assay...
August 26, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28837840/development-of-a-recombinant-yellow-fever-vector-expressing-a-hiv-clade-c-founder-envelope-gp120
#8
Jae-Sung Yu, Hua-Xin Liao, Jamie Pritchett, Cindy Bowman, Callie Vivian, Robert Parks, Shi-Mao Xia, Melissa Cooper, Wilton B Williams, Mattia Bonsignori, Steven G Reed, Meng Chen, Nathan Vandergrift, Charles M Rice, Barton F Haynes
Development of a HIV-1 vaccine is a major global priority. The yellow fever virus (YFV) attenuated vaccine 17D is among the most effective of currently used vaccines. However, the stability of the YFV17D vector when carrying non-flavivirus genes has been problematic. We have constructed and expressed HIV-1 Env in YFV17D with either single transmembrane (STM) or double transmembrane (DTM) YFV E protein domains for the development of anti-HIV antibodies. Here we describe modifications of the YFV17D vector such that HIV-1 Env gp120 is expressed in up to 5 passages in Vero cells...
August 31, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28832643/effect-of-naringin-on-gp120-induced-injury-mediated-by-p2x7-receptors-in-rat-primary-cultured-microglia
#9
Qiang Chen, Hui Wu, Jia Tao, Chenglong Liu, Zeyu Deng, Yang Liu, Guoqiao Chen, Baoyun Liu, Changshui Xu
Human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein 120 has been shown to activate microglia, causing release of inflammatory and toxic factors. The P2X7 receptor, primarily expressed on microglia, is closely associated with inflammation. Naringin, a plant bioflavonoid, has anti-inflammatory and anti-oxidative properties. We hypothesized that P2X7 receptor mediated gp120-induced injury in primary cultured microglia, and that naringin would have a protective effect. We showed that HIV-1 gp120 peptide (V3 loop, fragment 308-331) appeared to induce apoptosis of primary cultured microglia...
2017: PloS One
https://www.readbyqxmd.com/read/28832407/prevalence-and-clinical-impacts-of-hiv-1-intersubtype-recombinants-in-uganda-revealed-by-a-near-full-genome-population-and-deep-sequencing-approaches
#10
Guinevere Q Lee, David R Bangsberg, Theresa Mo, Chris Lachowski, Chanson J Brumme, Wendy Zhang, Viviane D Lima, Yap Boum, Bosco Bwana Mwebesa, Conrad Muzoora, Iren Andia, Yona Mbalibulha, Annet Kembabazi, Ryan Carroll, Mark J Siedner, Jessica E Haberer, A Rain Mocello, Simone H Kigozi, Peter W Hunt, Jeffrey N Martin, P Richard Harrigan
OBJECTIVES: To estimate prevalence, examine time trends, and test for clinical correlates and outcomes associated with HIV-1 intersubtype recombination under a full-genome sequencing context in a rural community in Mbarara, Uganda, where HIV-1 subtypes A1 and D co-circulate. METHODS: Near-full-genome HIV-1 Sanger sequence data was collected from plasma samples of 504 treatment-naïve individuals, who then received PI or NNRTI-containing regimens and were monitored for up to 7...
August 21, 2017: AIDS
https://www.readbyqxmd.com/read/28830144/layer-by-layer-engineered-microbicide-drug-delivery-system-targeting-hiv-1-gp120-physico-chemical-and-biological-properties
#11
Fohona S Coulibaly, Miezan J M Ezoulin, Sudhaunshu S Purohit, Navid J Avon, Nathan A Oyler, Bi Botti C Youan
The purpose of this study is to engineer a model anti-HIV microbicide (Tenofovir) drug delivery system targeting HIV-1 envelope glycoprotein gp120 (HIV-1 g120) for the prevention of HIV sexual transmission. HIV-1 g120 and mannose responsive particles (MRP) were prepared through the layer-by-layer coating of calcium carbonate (CaCO3) with Concanavalin A (Con A) and glycogen. MRP average particle size ranged from 881.7±15.45 nm to 1130±15.72 nm, depending on the number of Con A layers. Tenofovir encapsulation efficiency in CaCO3 was 74...
August 23, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28827122/new-anionic-carbosilane-dendrons-functionalized-with-a-do3a-ligand-at-the-focal-point-for-the-prevention-of-hiv-1-infection
#12
Silvia Moreno, Daniel Sepúlveda-Crespo, F Javier de la Mata, Rafael Gómez, Ma Ángeles Muñoz-Fernández
Novel third-generation polyanionic carbosilane dendrons with sulfonate or carboxylate end-groups and functionalized with a DO3A ligand at the focal point, and their corresponding copper complexes, have been prepared as antiviral compounds to prevent HIV-1 infection. The topology enables the compound to have an excellent chelating agent, DO3A, while keeping anionic peripheral groups for a therapeutic action. In this study, the cytotoxicity and anti-HIV-1 abilities of carboxylate- (5) or sulfonate-terminated (6) dendrons containing DO3A and their copper complexes (7 or 8) were evaluated...
August 18, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28827078/p2y12-shrna-treatment-relieved-hiv-gp120-induced-neuropathic-pain-in-rats
#13
Liran Shi, Bing Wu, Zhihua Yi, Shanhong Zhao, Lifang Zou, Lin Li, Huilong Yuan, Tianyu Jia, Shuangmei Liu, Hui Liu, Yun Gao, Guilin Li, Hong Xu, Chunping Zhang, Shangdong Liang
Human immunodeficiency virus (HIV) envelope glycoprotein (glycoprotein 120, gp120) can induce chronic neuropathic pain by directly stimulating primary sensory afferent neurons. Activation of satellite glial cells (SGCs) in dorsal root ganglia (DRG) plays an important role in the transmission of neuropathic pain. The P2Y12 receptor is expressed in SGCs of DRG. In this study, we investigated the role of the P2Y12 receptor in HIV gp120-induced neuropathic pain. The results showed that peripheral nerve exposure to HIV gp120 increased mechanical and thermal hyperalgesia in gp120-treated model rats...
August 18, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28814661/hdac-inhibition-induces-hiv-1-protein-and-enables-immune-based-clearance-following-latency-reversal
#14
Guoxin Wu, Michael Swanson, Aarthi Talla, Donald Graham, Julie Strizki, Daniel Gorman, Richard Jo Barnard, Wade Blair, Ole S Søgaard, Martin Tolstrup, Lars Østergaard, Thomas A Rasmussen, Rafick-Pierre Sekaly, Nancie M Archin, David M Margolis, Daria J Hazuda, Bonnie J Howell
Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein induction following treatment with LRAs...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28814519/extracellular-matrix-proteins-mediate-hiv-1-gp120-interactions-with-%C3%AE-4%C3%AE-7
#15
David Plotnik, Wenjin Guo, Brad Cleveland, Priska von Haller, Jimmy K Eng, Miklos Guttman, Kelly K Lee, James Arthos, Shiu-Lok Hu
Gut-homing α4β7(high) CD4(+) T lymphocytes have been shown to be preferentially targeted by Human Immunodeficiency Virus-1 (HIV), and are implicated in HIV pathogenesis. Previous studies demonstrated that HIV envelope protein gp120 binds and signals through α4β7, and that this likely contributes to the infection of α4β7(high) T cells and promotes cell-to-cell virus transmission. Structures within the second variable loop (V2) of gp120, including the tripeptide motif LDV/I, are thought to mediate gp120-α4β7 binding...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28814388/the-impact-of-poxvirus-vector-priming-protein-co-administration-and-vaccine-intervals-on-hiv-gp120-vaccine-elicited-antibody-magnitude-and-function-in-infant-macaques
#16
Bonnie Phillips, Genevieve G Fouda, Josh Eudailey, Justin Pollara, Alan D Curtis, Erika Kunz, Maria Dennis, Xiaoying Shen, Camden Bay, Michael Hudgens, David Pickup, S Munir Alam, Amir Ardeshir, Pamela A Kozlowski, Koen K A Van Rompay, Guido Ferrari, M Anthony Moody, Sallie Permar, Kristina De Paris
Despite success in reducing vertical HIV transmission by maternal antiretroviral therapy, several obstacles limit its efficacy during breastfeeding, and breast-milk transmission is now the dominant mode of mother-to-child transmission (MTCT) of HIV in infants. Thus, a pediatric vaccine is needed to eradicate oral HIV infections in newborns and infants. Utilizing the infant rhesus macaque model, we compared 3 different vaccine regimens: (i) HIV Env protein only; (ii) a poxvirus vector (MVA)-HIV Env prime/HIV Env protein boost, and (iii) co-administration of HIV Env protein and MVA-HIV Env at all time points...
August 16, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28811543/4-e-p-tolylimino-methylbenzene-1-2-diol-timbd-suppresses-hiv1-gp120-mediated-production-of-il6-and-il8-but-not-ccl5
#17
Fatma Abdalla, Anantha Nookala, Subhash B Padhye, Anil Kumar, Hari K Bhat
Human immunodeficiency virus (HIV) has been associated with inflammatory effects that may potentially result in neurodegenerative changes and a number of newer chemotherapeutic agents are being tested to ameliorate these effects. In this study, we investigated the anti-neuroinflammatory activity of a novel resveratrol analog 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD) against HIV1-gp120 induced neuroinflammation in SVG astrocytes. SVG astrocytic cells were pretreated with TIMBD or resveratrol (RES) and then transfected with a plasmid encoding HIV1-gp120...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794027/hiv-dna-adenovirus-multiclade-envelope-vaccine-induces-gp41-antibody-immunodominance-in-rhesus-macaques
#18
Qifeng Han, Wilton B Williams, Kevin O Saunders, Kelly E Seaton, Kevin J Wiehe, Nathan Vandergrift, Tarra Von Holle, Ashley M Trama, Robert J Parks, Kan Luo, Thaddeus C Gurley, Thomas B Kepler, Dawn J Marshall, David C Montefiori, Laura L Sutherland, Munir S Alam, John F Whitesides, Cindy Bowman, Sallie R Permar, Barney S Graham, John R Mascola, Patrick C Seed, Koen K A Van Rompay, Georgia D Tomaras, Michael A Moody, Barton F Haynes
Dominant antibody responses in vaccinees who received the multiclade (A, B and C) envelope (Env) DNA/rAd5 vaccine studied in the HIV-1 vaccine trials network (HVTN) efficacy trial 505 (HVTN 505), targeted Env gp41 and cross-reacted with microbial antigens. In this study, we asked if the DNA/rAd5 vaccine induced a similar antibody response in rhesus macaques (RMs) that are commonly used as an animal model for human HIV-1 infections and for testing candidate HIV-1 vaccines. We also asked if gp41 immunodominance could be avoided by immunization of neonatal RMs during the early stages of microbial colonization...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28794022/potent-in-vivo-nk-cell-mediated-elimination-of-hiv-1-infected-cells-mobilized-by-a-gp120-bispecific-and-hexavalent-broadly-neutralizing-fusion-protein
#19
Ariola Bardhi, Yanling Wu, Weizao Chen, Zhongyu Zhu, Jian Hua Zheng, Hing Wong, Emily Jeng, Jennifer Jones, Christina Ochsenbauer, John C Kappes, Dimiter S Dimitrov, Tianlei Ying, Harris Goldstein
Antibodies bound to HIV-1 envelope protein expressed by infected cells mobilize antibody dependent cellular cytotoxicity (ADCC) to eliminate the HIV-1-infected cells and thereby suppress HIV-1 infection and delay disease progression. Studies treating HIV-1-infected individuals with latency reactivation agents to reduce their latent HIV-1 reservoirs indicated that their HIV-1-specific immune responses were insufficient to effectively eliminate the reactivated latent HIV-1-infected T cells. Mobilization of ADCC may facilitate elimination of reactivated latent HIV-1-infected cells to deplete the HIV-1 reservoir and contribute to functional HIV-1 cure...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28790381/selective-cytotoxicity-of-a-novel-immunotoxin-based-on-pulchellin-a-chain-for-cells-expressing-hiv-envelope
#20
Mohammad Sadraeian, Francisco E G Guimarães, Ana P U Araújo, David K Worthylake, Louis Jr LeCour, Seth H Pincus
Immunotoxins (ITs), which consist of antibodies conjugated to toxins, have been proposed as a treatment for cancer and chronic infections. To develop and improve the ITs, different toxins such as ricin, have been used, aiming for higher efficacy against target cells. The toxin pulchellin, isolated from the Abrus pulchellus plant, has similar structure and function as ricin. Here we have compared two plant toxins, recombinant A chains from ricin (RAC) and pulchellin (PAC) toxins, for their ability to kill HIV Env-expressing cells...
August 8, 2017: Scientific Reports
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