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https://www.readbyqxmd.com/read/29463701/bone-degradation-machinery-of-osteoclasts-an-hiv-1-target-that-contributes-to-bone-loss
#1
Brigitte Raynaud-Messina, Lucie Bracq, Maeva Dupont, Shanti Souriant, Shariq M Usmani, Amsha Proag, Karine Pingris, Vanessa Soldan, Christophe Thibault, Florence Capilla, Talal Al Saati, Isabelle Gennero, Pierre Jurdic, Paul Jolicoeur, Jean-Luc Davignon, Thorsten R Mempel, Serge Benichou, Isabelle Maridonneau-Parini, Christel Vérollet
Bone deficits are frequent in HIV-1-infected patients. We report here that osteoclasts, the cells specialized in bone resorption, are infected by HIV-1 in vivo in humanized mice and ex vivo in human joint biopsies. In vitro, infection of human osteoclasts occurs at different stages of osteoclastogenesis via cell-free viruses and, more efficiently, by transfer from infected T cells. HIV-1 infection markedly enhances adhesion and osteolytic activity of human osteoclasts by modifying the structure and function of the sealing zone, the osteoclast-specific bone degradation machinery...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29420192/mechanism-of-stx17-recruitment-to-autophagosomes-via-irgm-and-mammalian-atg8-proteins
#2
Suresh Kumar, Ashish Jain, Farzin Farzam, Jingyue Jia, Yuexi Gu, Seong Won Choi, Michal H Mudd, Aurore Claude-Taupin, Michael J Wester, Keith A Lidke, Tor-Erik Rusten, Vojo Deretic
Autophagy is a conserved eukaryotic process with metabolic, immune, and general homeostatic functions in mammalian cells. Mammalian autophagosomes fuse with lysosomes in a SNARE-driven process that includes syntaxin 17 (Stx17). How Stx17 translocates to autophagosomes is unknown. In this study, we show that the mechanism of Stx17 recruitment to autophagosomes in human cells entails the small guanosine triphosphatase IRGM. Stx17 directly interacts with IRGM, and efficient Stx17 recruitment to autophagosomes requires IRGM...
February 2, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29415006/a-single-%C3%AE-octyl-glucoside-molecule-induces-hiv-1-nef-dimer-formation-in-the-absence-of-partner-protein-binding
#3
Mousheng Wu, John J Alvarado, Corinne E Augelli-Szafran, Roger G Ptak, Thomas E Smithgall
The HIV-1 Nef accessory protein is essential for viral pathogenicity and AIDS progression. Nef forms complexes with multiple host cell factors to facilitate viral replication and promote immune escape of HIV-infected cells. Previous X-ray crystal structures demonstrate that Nef forms homodimers, the orientation of which are influenced by host cell binding partners. In cell-based fluorescence complementation assays, Nef forms homodimers at the plasma membrane. However, recombinant Nef proteins often exist as monomers in solution, suggesting that membrane interaction may also trigger monomer to dimer transitions...
2018: PloS One
https://www.readbyqxmd.com/read/29404888/hiv-1-nef-cawleaq-motif-a-regulator-of-monocytes-invasion-through-eno1-modulation
#4
Reshu Saxena, Umesh Kumar Vekariya, Pradeep Kumar, Amit Kumar Tripathi, Jimut Kanti Ghosh, Raj Kamal Tripathi
HIV-1 transmission and spread involves significant host-virus interaction. Possible targets for obstacle of HIV-1 lie at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and leads their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. For the viral infectivity and pathogenicity, HIV-1 Nef facilitates immune evasion through protein-protein interactions within host cell. HIV-1 Nef is significant for viral infectivity and pathogenicity...
February 5, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29389981/a-high-hiv-1-strain-variability-in-london-uk-revealed-by-full-genome-analysis-results-from-the-iconic-project
#5
Gonzalo Yebra, Dan Frampton, Tiziano Gallo Cassarino, Jade Raffle, Jonathan Hubb, R Bridget Ferns, Laura Waters, C Y William Tong, Zisis Kozlakidis, Andrew Hayward, Paul Kellam, Deenan Pillay, Duncan Clark, Eleni Nastouli, Andrew J Leigh Brown
BACKGROUND & METHODS: The ICONIC project has developed an automated high-throughput pipeline to generate HIV nearly full-length genomes (NFLG, i.e. from gag to nef) from next-generation sequencing (NGS) data. The pipeline was applied to 420 HIV samples collected at University College London Hospitals NHS Trust and Barts Health NHS Trust (London) and sequenced using an Illumina MiSeq at the Wellcome Trust Sanger Institute (Cambridge). Consensus genomes were generated and subtyped using COMET, and unique recombinants were studied with jpHMM and SimPlot...
2018: PloS One
https://www.readbyqxmd.com/read/29386131/a-long-cytoplasmic-loop-governs-the-sensitivity-of-the-anti-viral-host-protein-serinc5-to-hiv-1-nef
#6
Weiwei Dai, Yoshiko Usami, Yuanfei Wu, Heinrich Göttlinger
We recently identified the multipass transmembrane protein SERINC5 as an antiviral protein that can potently inhibit HIV-1 infectivity and is counteracted by HIV-1 Nef. We now report that the anti-HIV-1 activity, but not the sensitivity to Nef, is conserved among vertebrate SERINC5 proteins. However, a Nef-resistant SERINC5 became Nef sensitive when its intracellular loop 4 (ICL4) was replaced by that of Nef-sensitive human SERINC5. Conversely, human SERINC5 became resistant to Nef when its ICL4 was replaced by that of a Nef-resistant SERINC5...
January 23, 2018: Cell Reports
https://www.readbyqxmd.com/read/29364927/viral-protein-nef-is-detected-in-plasma-of-half-of-hiv-infected-adults-with-undetectable-plasma-hiv-rna
#7
Jana Ferdin, Katja Goričar, Vita Dolžan, Ana Plemenitaš, Jeffrey N Martin, Boris M Peterlin, Steven G Deeks, Metka Lenassi
OBJECTIVE: To address the role of translationally active HIV reservoir in chronic inflammation and non-AIDS related disorders, we first need a simple and accurate assay to evaluate viral protein expression in virally suppressed subjects. DESIGN: We optimized an HIV Nef enzyme-linked immunosorbent assay (ELISA) and used it to quantify plasma Nef levels as an indicator of the leaky HIV reservoir in an HIV-infected cohort. METHODS: This study accessed 134 plasma samples from a well-characterized cohort study of HIV-infected and uninfected adults in San Francisco (the SCOPE cohort)...
2018: PloS One
https://www.readbyqxmd.com/read/29338738/rapid-hiv-disease-progression-following-superinfection-in-an-hla-b-27-05-b-57-01-positive-transmission-recipient
#8
Jacqui Brener, Astrid Gall, Jacob Hurst, Rebecca Batorsky, Nora Lavandier, Fabian Chen, Anne Edwards, Chrissy Bolton, Reena Dsouza, Todd Allen, Oliver G Pybus, Paul Kellam, Philippa C Matthews, Philip J R Goulder
BACKGROUND: The factors determining differential HIV disease outcome among individuals expressing protective HLA alleles such as HLA-B*27:05 and HLA-B*57:01 remain unknown. We here analyse two HIV-infected subjects expressing both HLA-B*27:05 and HLA-B*57:01. One subject maintained low-to-undetectable viral loads for more than a decade of follow up. The other progressed to AIDS in < 3 years. RESULTS: The rapid progressor was the recipient within a known transmission pair, enabling virus sequences to be tracked from transmission...
January 16, 2018: Retrovirology
https://www.readbyqxmd.com/read/29334757/high-prevalence-of-non-b-hiv-1-subtypes-in-overseas-sailors-and-prostitutes-in-korea
#9
Young-Keol Cho, Jung Eun Kim, Brian Thomas Foley
There have been no studies related to groups at the highest risk for HIV-1 infection in Korea before 1993. Here, for the first time, we report the distribution of HIV subtypes in overseas sailors (OSs), and prostitutes who worked in brothels near US military bases in Korea. We retrospectively determined the sequences of nef in 131 patients using RT-PCR. These patients comprised of 102 OSs, 14 OS spouses, and 15 prostitutes. Phylogenetic analysis was performed using 128 Korean OSs, OS spouses, and prostitutes...
January 15, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29329537/the-hiv-1-accessory-proteins-nef-and-vpu-downregulate-total-and-cell-surface-cd28-in-cd4-t-cells
#10
Emily N Pawlak, Brennan S Dirk, Rajesh Abraham Jacob, Aaron L Johnson, Jimmy D Dikeakos
BACKGROUND: The HIV-1 accessory proteins Nef and Vpu alter cell surface levels of multiple host proteins to modify the immune response and increase viral persistence. Nef and Vpu can downregulate cell surface levels of the co-stimulatory molecule CD28, however the mechanism of this function has not been completely elucidated. RESULTS: Here, we provide evidence that Nef and Vpu decrease cell surface and total cellular levels of CD28. Moreover, using inhibitors we implicate the cellular degradation machinery in the downregulation of CD28...
January 12, 2018: Retrovirology
https://www.readbyqxmd.com/read/29258818/remodeling-of-hiv-1-nef-structure-by-src-family-kinase-binding
#11
Jamie A Moroco, John Jeff Alvarado, Ryan P Staudt, Haibin Shic, Thomas E Wales, Thomas E Smithgall, John R Engen
The HIV-1 accessory protein Nef controls multiple aspects of the viral life cycle and host immune response, making it an attractive therapeutic target. Previous X-ray crystal structures of Nef in complex with key host cell binding partners have shed light on protein-protein interactions critical to Nef function. Crystal structures of Nef in complex with either the SH3 or tandem SH3-SH2 domains of Src-family kinases reveal distinct dimer conformations of Nef. However, the existence of these Nef dimer complexes in solution has not been established...
December 16, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29237835/hla-class-i-mediated-hiv-1-control-in-vietnamese-infected-with-hiv-1-subtype-a-e
#12
Takayuki Chikata, Giang Van Tran, Hayato Murakoshi, Tomohiro Akahoshi, Ying Qi, Vivek Naranbhai, Nozomi Kuse, Yoshiko Tamura, Madoka Koyanagi, Sachiko Sakai, Dung Hoai Nguyen, Dung Thi Nguyen, Ha Thu Nguyen, Trung Vu Nguyen, Shinichi Oka, Maureen P Martin, Mary Carrington, Keiko Sakai, Kinh Van Nguyen, Masafumi Takiguchi
HIV-1-specific cytotoxic T cells (CTLs) play an important role in the control of HIV-1 subtype B or C infection. However, the role of CTLs in HIV-1 subtype A/E infection still remains unclear. Here we investigated the association of HLA class I alleles with clinical outcome in treatment-naïve Vietnamese infected with subtype A/E. We found that HLA-C*12:02 was significantly associated with lower pVL and higher CD4 count and that the HLA-A*29:01-B*07:05-C*15:05 haplotype was significantly associated with higher pVL and lower CD4 count as compared to individuals without these respective genotypes...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29237831/maintenance-of-ap-2-dependent-functional-activities-of-nef-restricts-pathways-of-immune-escape-from-cd8-t-lymphocyte-responses
#13
Blake Schouest, Andrea M Weiler, Sanath Kumar Janaka, T Alix Myers, Arpita Das, Sarah C Wilder, Jessica Furlott, Melody Baddoo, Erik K Flemington, Eva G Rakasz, David T Evans, Thomas C Friedrich, Nicholas J Maness
Nef-specific CD8+ T lymphocytes (CD8TL) are linked to extraordinary control of primate lentiviral replication, but the mechanisms underlying their efficacy remain largely unknown. The immunodominant, Mamu-B*017:01+ restricted Nef195-203MW9 epitope in SIVmac239 partially overlaps a sorting motif important for interactions with host AP-2 proteins and, hence, downmodulation of several host proteins including Tetherin (CD317/BST-2), CD28, CD4, SERINC3, and SERINC5. We reasoned that CD8TL-driven evolution in this epitope might compromise Nef's ability to modulate these important molecules...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29167337/differential-immunodominance-hierarchy-of-cd8-t-cell-responses-in-hla-b-27-05-and-b-27-02-mediated-control-of-hiv-1-infection
#14
Emily Adland, Matilda Hill, Nora Lavandier, Anna Csala, Anne Edwards, Fabian Chen, Marek Radkowski, Justyna D Kowalska, Dimitrios Paraskevis, Angelos Hatzakis, Humberto Valenzuela-Ponce, Katja Pfafferott, Ian Williams, Pierre Pellegrino, Persephone Borrow, Masahiko Mori, Jürgen Rockstroh, Julia G Prado, Beatriz Mothe, Judith Dalmau, Javier Martinez-Picado, Gareth Tudor-Williams, John Frater, Anette Stryhn, Soren Buus, Gustavo Reyes Teran, Simon Mallal, Mina John, Susan Buchbinder, Gregory Kirk, Jeffrey Martin, Nelson Michael, Jacques Fellay, Steve Deeks, Bruce Walker, Santiago Avila-Rios, David Cole, Christian Brander, Mary Carrington, Philip Goulder
The well-characterised association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8+ T-cell responses towards the conserved Gag 263-272 ('KK10') and Pol 901-909 'KY9' epitopes. We here studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely-related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 associate with slower disease progression and lower viral loads...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29114997/in-vitro-modeling-of-hiv-proviral-activity-in-microglia
#15
Lee A Campbell, Christopher T Richie, Yajun Zhang, Emily J Heathward, Lamarque M Coke, Emily Y Park, Brandon K Harvey
Microglia, the resident macrophages of the brain, play a key role in the pathogenesis of HIV-associated neurocognitive disorders (HAND) due to their productive infection by HIV. This results in the release of neurotoxic viral proteins and pro-inflammatory compounds which negatively affect the functionality of surrounding neurons. Because models of HIV infection within the brain are limited, we aimed to create a novel microglia cell line with an integrated HIV provirus capable of recreating several hallmarks of HIV infection...
November 8, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29063512/brain-specific-hiv-nef-identified-in-multiple-patients-with-neurological-disease
#16
Susanna L Lamers, Gary B Fogel, Enoch S Liu, Andrew E Barbier, Christopher W Rodriguez, Elyse J Singer, David J Nolan, Rebecca Rose, Michael S McGrath
HIV-1 Nef is a flexible, multifunctional protein with several cellular targets that is required for pathogenicity of the virus. This protein maintains a high degree of genetic variation among intra- and inter-host isolates. HIV Nef is relevant to HIV-associated neurological diseases (HAND) in patients treated with combined antiretroviral therapy because of the protein's role in promoting survival and migration of infected brain macrophages. In this study, we analyzed 2020 HIV Nef sequences derived from 22 different tissues and 31 subjects using a novel computational approach...
October 23, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/29061065/improving-the-potency-of-dna-vaccine-encoding-hiv-1-nef-antigen-using-two-endogenous-adjuvants-in-mouse-model
#17
B S Jafarzade, S M Sadat, R Yaghobi, A Bolhassani
BACKGROUND: DNA immunization can induce long-term immune responses, which are required to design an effective HIV vaccine. It was shown that antigen-expressing plasmids can increase the protective immunity against infectious diseases such as: influenza and malaria. However, DNA-based immunizations have poor immunogenicity, thus the use of potent immunoadjuvants can enhance their potency. METHODS: In the current study, preparation of the recombinant HIV-1 Nef, Gp96 and HMGB1 DNA constructs was performed in bacterial system...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29046444/relative-resistance-of-mhc-b-to-nef-mediated-downregulation-is-conserved-among-primate-lentiviruses-and-influences-antiviral-t-cell-responses-in-hiv-1-infected-individuals
#18
Francis Mwimanzi, Mako Toyoda, Macdonald Mahiti, Jaclyn K Mann, Jeffrey N Martin, David Bangsberg, Mark A Brockman, Philip Goulder, Frank Kirchhoff, Zabrina L Brumme, Thumbi Ndung'u, Takamasa Ueno
Patient-derived HIV-1 subtype B Nef clones downregulate HLA-A more efficiently than HLA-B. However, it remains unknown whether this property is common to Nef proteins across primate lentiviruses, and how antiviral immune responses may be affected. We examined 263 Nef clones from diverse primate lentiviruses including different pandemic HIV-1 group M subtypes for their ability to downregulate MHC-A and MHC-B from the cell surface. Though lentiviral Nef proteins differed markedly in their absolute MHC-A and MHC-B downregulation abilities, all lentiviral Nef lineages downregulated MHC-A on average 11-32% more efficiently than MHC-B...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29028477/modulation-of-the-nf-%C3%AE%C2%BAb-signaling-pathway-by-the-hiv-2-envelope-glycoprotein-and-its-incomplete-bst-2-antagonism
#19
François E Dufrasne, Mara Lucchetti, Anandi Martin, Emmanuel André, Géraldine Dessilly, Benoit Kabamba, Patrick Goubau, Jean Ruelle
The HIVs have evolved by selecting means to hijack numerous host cellular factors. HIVs exploit the transcription factor NF-κB to ensure efficient LTR-driven gene transcription. However, NF-κB is primarily known to act as a key regulator of the proinflammatory and antiviral responses. Interestingly, retroviruses activate NF-κB during early stages of infection to initiate proviral genome expression while suppressing it at later stages to restrain expression of antiviral genes. During HIV-1 infection, diverse viral proteins such as Env, Nef and Vpr have been proposed to activate NF-κB activity, whereas Vpu has been shown to inhibit NF-κB activation...
October 10, 2017: Virology
https://www.readbyqxmd.com/read/28972547/human-immunodeficiency-virus-proteins-mimic-human-t-cell-receptors-inducing-cross-reactive-antibodies
#20
Robert Root-Bernstein
Human immunodeficiency virus (HIV) hides from the immune system in part by mimicking host antigens, including human leukocyte antigens. It is demonstrated here that HIV also mimics the V-β-D-J-β of approximately seventy percent of about 600 randomly selected human T cell receptors (TCR). This degree of mimicry is greater than any other human pathogen, commensal or symbiotic organism studied. These data suggest that HIV may be evolving into a commensal organism just as simian immunodeficiency virus has done in some types of monkeys...
October 3, 2017: International Journal of Molecular Sciences
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