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https://www.readbyqxmd.com/read/28642743/hiv-1-nef-signaling-in-intestinal-mucosa-epithelium-suggests-the-existence-of-an-active-inter-kingdom-crosstalk-mediated-by-exosomes
#1
REVIEW
Cristina Felli, Olimpia Vincentini, Marco Silano, Andrea Masotti
The human intestinal mucosal surface represents the first defense against pathogens and regulates the immune response through the combination of epithelial cell (EC) functions and immunological factors. ECs act as sensors of luminal stimuli and interact with the immune cells through signal-transduction pathways, thus representing the first barrier that HIV-1 virus encounters during infection. In particular, the HIV-1 Nef protein plays a crucial role in viral invasion and replication. Nef is expressed early during viral infection and interacts with numerous cellular proteins as a scaffold/adaptor...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28615199/impaired-downregulation-of-nkg2d-ligands-by-nef-protein-from-elite-controllers-sensitizes-hiv-1-infected-cells-to-adcc
#2
Nirmin Alsahafi, Jonathan Richard, Jérémie Prévost, Mathieu Coutu, Nathalie Brassard, Matthew S Parsons, Daniel E Kaufmann, Mark Brockman, Andrés Finzi
HIV-1 Nef clones isolated from a rare subset of HIV-1-infected elite controllers (EC), with the ability to suppress viral load to undetectable levels in the absence of antiretroviral therapy, are unable to fully downregulate CD4 from the plasma membrane of CD4+ T cells. Residual CD4 left at the plasma membrane allows Env-CD4 interaction, which leads to increased exposure of Env CD4-induced epitopes and increases susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). ADCC is mediated largely by natural killer (NK) cells, which control their activation status through the cumulative signals received through activating and inhibitory receptors...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28602843/combination-of-cell-penetrating-peptides-and-heterologous-dna-prime-protein-boost-strategy-enhances-immune-responses-against-hiv-1-nef-antigen-in-balb-c-mouse-model
#3
Somayeh Kadkhodayan, Behnaz Sadat Jafarzade, Seyed Mehdi Sadat, Fateme Motevalli, Elnaz Agi, Azam Bolhassani
To develop a strong HIV specific T-cell response, the HIV-1 Tat and Nef regulatory proteins have been known as attractive antigenic candidates in vaccine design. A peptide transduction domain of Tat (48-60 aa) could act to deliver other therapeutic molecules into different cells. In this line, several cell-penetrating peptides (CPPs) have been designed to transfer DNA, siRNA, polypeptides and proteins into cells through non-covalent approach such as CADY and PEP families. Some studies showed that the endogenous adjuvants including heat shock protein Gp96 could stimulate antigen-specific T cell immune responses...
June 8, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28586246/characterization-of-a-new-hiv-1-crf01_ae-crf07_bc-recombinant-virus-in-guangxi-china
#4
Desheng Kong, Yan Wang, Chen Wang, Shujia Liang, Yi Feng, Yuhua Ruan, Yiming Shao, Liying Ma
Currently, more and more kinds of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) were identified in China. A novel second-generation CCR5-tropic HIV-1 recombinant virus (GX2016EU09) was identified here, which was isolated from a HIV-1 infected man who had sex with men (MSM) in Guangxi, China. Phylogenetic analysis of near full-length genome (NFLG) showed that the novel HIV-1 recombinant GX2016EU09 clustered with CRF01_AE reference sequences, but set up a distinct branch. Recombinant analysis showed that the NFLG of GX2016EU09 composed of CRF01_AE (as the backbone) and CRF07_BC, with 9 recombination break points observed in the gag, pol, vif, vpr, tat, rev, vpu, env and nef regions...
June 6, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28577469/the-interaction-between-hiv-1-nef-and-adaptor-protein-2-reduces-nef-mediated-cd4-t-cell-apoptosis
#5
Rajesh Abraham Jacob, Aaron L Johnson, Emily N Pawlak, Brennan S Dirk, Logan R Van Nynatten, S M Mansour Haeryfar, Jimmy D Dikeakos
Acquired Immune Deficiency Syndrome is characterized by a decline in CD4(+) T cells. Here, we elucidated the mechanism underlying apoptosis in Human Immunodeficiency Virus-1 (HIV-1) infection by examining host apoptotic pathways hijacked by the HIV-1 Nef protein in the CD4(+) T-cell line Sup-T1. Using a panel of Nef mutants unable to bind specific host proteins we uncovered that Nef generates pro- and anti-apoptotic signals. Apoptosis increased upon mutating the motifs involved in the interaction of Nef:AP-1 (NefM20A or NefEEEE62-65AAAA) or Nef:AP-2 (NefLL164/165AA), implying these interactions limit Nef-mediated apoptosis...
May 31, 2017: Virology
https://www.readbyqxmd.com/read/28574482/immunologic-and-virologic-mechanisms-for-partial-protection-from-intravenous-challenge-by-an-integration-defective-siv-vaccine
#6
Chu Wang, Chunlai Jiang, Nan Gao, Kaikai Zhang, Donglai Liu, Wei Wang, Zhe Cong, Chuan Qin, Vitaly V Ganusov, Guido Ferrari, Celia LaBranche, David C Montefiori, Wei Kong, Xianghui Yu, Feng Gao
The suppression of viral loads and identification of selection signatures in non-human primates after challenge are indicators for effective human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccines. To mimic the protective immunity elicited by attenuated SIV vaccines, we developed an integration-defective SIV (idSIV) vaccine by inactivating integrase, mutating sequence motifs critical for integration, and inserting the cytomegalovirus (CMV) promoter for more efficient expression in the SIVmac239 genome...
June 2, 2017: Viruses
https://www.readbyqxmd.com/read/28540766/hiv-1-full-genome-phylogenetics-of-generalized-epidemics-in-sub-saharan-africa-impact-of-missing-nucleotide-characters-in-next-generation-sequences
#7
Oliver Ratmann, Chris Wymant, Caroline Colijn, Siva Danaviah, M Essex, Simon D W Frost, Astrid Gall, Simani Gaiseitsiwe, Mary Grabowski, Ronald Gray, Stephane Guindon, Arndt von Haeseler, Pontiano Kaleebu, Michelle Kendall, Alexey Kozlov, Justen Manasa, Bui Quang Minh, Sikhulile Moyo, Vladimir Novitsky, Rebecca Nsubuga, Sureshnee Pillay, Thomas C Quinn, David Serwadda, Deogratius Ssemwanga, Alexandros Stamatakis, Jana Trifinopoulos, Maria Wawer, Andrew Leigh Brown, Tulio de Oliveira, Paul Kellam, Deenan Pillay, Christophe Fraser
To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the 'Phylogenetics and Networks for Generalised HIV Epidemics in Africa' consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n=2,833; MRC/UVRI Uganda, n=701; Mochudi Prevention Project, n=359; Africa Health Research Institute Resistance Cohort, n=92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai...
May 25, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28500742/amino-acids-at-positions-3-168-and-169-are-associated-with-the-ability-of-nef-proteins-from-hiv-1-crf01_ae-to-downmodulate-cd4
#8
Wen-Dong Kuang, Yan-Heng Zhou, Ping Zhong, Chiyu Zhang, Jian-Hua Wang
Several HIV-1 subtypes are co-circulating among various high-risk groups in China, and an increasing prevalence of CRF01_AE was observed among MSM (men who have sex with men) within recent years. Patients infected with CRF01_AE may experience a more rapid disease progression than patients infected with non-CRF01_AE; however, the underlying mechanisms remains elusive. HIV-1 Nef is a multifunctional protein and plays critical roles in viral pathogenesis. Nef downregulates CD4 and human leukocyte antigen (HLA) to promote viral transmission and escape from the host immune response...
May 13, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28479111/co-utilization-of-a-tlr5-agonist-and-nano-formulation-of-hiv-1-vaccine-candidate-leads-to-increased-vaccine-immunogenicity-and-decreased-immunogenic-dose-a-preliminary-study
#9
Hajar Rostami, Masoumeh Ebtekar, Mehdi Shafiee Ardestani, Mohammad Hossein Yazdi, Mehdi Mahdavi
Vaccines currently available for AIDS show poor efficiency, demonstrating the need for new strategies to increase their immunogenicity. In this study, the HIV-1P24-Nef peptide was used as a model vaccine, followed by utilization of a novel strategy to increase its immunogenicity. There is a growing interest in using TLR agonists for vaccine formulations. Such molecules bind to their receptors on immune cells, especially the cell surface of antigen presenting cells, thereby activating these cells and inflammatory responses...
May 4, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28431573/a-highly-pathogenic-simian-human-immunodeficiency-virus-effectively-produces-infectious-virions-compared-with-a-less-pathogenic-virus-in-cell-culture
#10
Shoya Iwanami, Yusuke Kakizoe, Satoru Morita, Tomoyuki Miura, Shinji Nakaoka, Shingo Iwami
BACKGROUND: The host range of human immunodeficiency virus (HIV) is quite narrow. Therefore, analyzing HIV-1 pathogenesis in vivo has been limited owing to lack of appropriate animal model systems. To overcome this, chimeric simian and human immunodeficiency viruses (SHIVs) that encode HIV-1 Env and are infectious to macaques have been developed and used to investigate the pathogenicity of HIV-1 in vivo. So far, we have many SHIV strains that show different pathogenesis in macaque experiments...
April 21, 2017: Theoretical Biology & Medical Modelling
https://www.readbyqxmd.com/read/28370302/comparative-genetic-variability-in-hiv-1-subtype-c-nef-gene-in-early-age-groups-of-infants
#11
Uma Sharma, Poonam Gupta, Megha Singhal, Supriya Singh, Sunil Gupta, Srinivas Venkatesh, Arvind Rai, Mohammad Husain
Targeting properties of vertically transmitted viruses in early infancy is important to understand disease progression. To investigate genotypic characteristics of transmitted viruses, blood samples were obtained from infants aged 6 weeks-18 months, categorized in two age groups, acute (<6 months) and early (>6-18 months). Nef having an important role in pathogenesis was selected to explore the viral characteristics. A total of 57 PCR positive samples, amplified by nef gene were sequenced. Analysis showed that 50 sequences belonged to subtype C...
March 31, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28348557/dendritic-cell-response-to-hiv-1-is-controlled-by-differentiation-programs-in-the-cells-and-strain-specific-properties-of-the-virus
#12
Aikaterini Nasi, Sylvie Amu, Mårten Göthlin, Marianne Jansson, Noemi Nagy, Francesca Chiodi, Bence Réthi
Dendritic cells (DCs) are potent antigen-presenting cells that might play contradictory roles during HIV-1 infection, contributing not only to antiviral immunity but also to viral dissemination and immune evasion. Although DCs are characterized by enormous functional diversity, it has not been analyzed how differentially programmed DCs interact with HIV-1. We have previously described the reprogramming of DC development by endogenously produced lactic acid that accumulated in a cell culture density-dependent manner and provided a long-lasting anti-inflammatory signal to the cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28331088/bst-2-expression-modulates-small-cd4-mimetic-sensitization-of-hiv-1-infected-cells-to-antibody-dependent-cellular-cytotoxicity
#13
Jonathan Richard, Jérémie Prévost, Benjamin von Bredow, Shilei Ding, Nathalie Brassard, Halima Medjahed, Mathieu Coutu, Bruno Melillo, Frédéric Bibollet-Ruche, Beatrice H Hahn, Daniel E Kaufmann, Amos B Smith, Joseph Sodroski, Daniel Sauter, Frank Kirchhoff, Katrina Gee, Stuart J Neil, David T Evans, Andrés Finzi
Antibodies recognizing conserved CD4-induced (CD4i) epitopes on human immunodeficiency virus type 1 (HIV-1) Env and able to mediate antibody-dependent cellular cytotoxicity (ADCC) have been shown to be present in sera from most HIV-1-infected individuals. These antibodies preferentially recognize Env in its CD4-bound conformation. CD4 downregulation by Nef and Vpu dramatically reduces exposure of CD4i HIV-1 Env epitopes and therefore reduce the susceptibility of HIV-1-infected cells to ADCC mediated by HIV-positive (HIV+) sera...
June 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28275375/a-comparative-phase-i-study-of-combination-homologous-subtype-c-dna-mva-and-env-gp140-protein-adjuvant-hiv-vaccines-in-two-immunization-regimes
#14
Sarah Joseph, Killian Quinn, Aldona Greenwood, Alethea V Cope, Paul F McKay, Peter J Hayes, Jakub T Kopycinski, Jill Gilmour, Aleisha N Miller, Christof Geldmacher, Yuka Nadai, Mohamed I M Ahmed, David C Montefiori, Len Dally, George Bouliotis, David J M Lewis, Roger Tatoud, Ralf Wagner, Mariano Esteban, Robin J Shattock, Sheena McCormack, Jonathan Weber
There remains an urgent need for a prophylactic HIV vaccine. We compared combined MVA and adjuvanted gp140 to sequential MVA/gp140 after DNA priming. We expected Env-specific CD4+ T-cells after DNA and MVA priming, and Env-binding antibodies in 100% individuals after boosting with gp140 and that combined vaccines would not compromise safety and might augment immunogenicity. Forty volunteers were primed three times with DNA plasmids encoding (CN54) env and (ZM96) gag-pol-nef at 0, 4 and 8 weeks then boosted with MVA-C (CN54 env and gag-pol-nef) and glucopyranosyl lipid adjuvant-aqueous formulation (GLA-AF) adjuvanted CN54gp140...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28275190/identification-of-serinc5-001-as-the-predominant-spliced-isoform-for-hiv-1-restriction
#15
Xianfeng Zhang, Tao Zhou, Jie Yang, Yumei Lin, Jing Shi, Xihe Zhang, Dylan A Frabutt, Xiangwei Zeng, Sunan Li, Patrick J Venta, Yong-Hui Zheng
Among the five serine incorporator (SERINC) family members, SERINC5 (Ser5) was reported to strongly inhibit HIV-1 replication, which is counteracted by Nef. Ser5 produces 5 alternatively spliced isoforms: Ser5-001 has 10 putative transmembrane domains, whereas Ser5-004, -005, -008a, and -008b do not have the last one. Here, we confirmed the strong Ser5 anti-HIV-1 activity and investigated its isoforms' expression and antiviral activities. It was found that Ser5-001 transcripts were detected at least 10-fold more than the other isoforms by real-time quantitative PCR...
May 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28261165/primate-lentiviruses-modulate-nf-%C3%AE%C2%BAb-activity-by-multiple-mechanisms-to-fine-tune-viral-and-cellular-gene-expression
#16
REVIEW
Elena Heusinger, Frank Kirchhoff
The transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) plays a complex role during the replication of primate lentiviruses. On the one hand, NF-κB is essential for induction of efficient proviral gene expression. On the other hand, this transcription factor contributes to the innate immune response and induces expression of numerous cellular antiviral genes. Recent data suggest that primate lentiviruses cope with this challenge by boosting NF-κB activity early during the replication cycle to initiate Tat-driven viral transcription and suppressing it at later stages to minimize antiviral gene expression...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28255725/studying-the-immune-synapse-in-hiv-1-infection
#17
Iratxe Del Río-Iñiguez, Jérôme Bouchet, Andrés Alcover
T cells are the main cellular targets of the human immunodeficiency virus 1 (HIV-1). HIV-1 infection induces pleiotropic effects on the infected T cell that modify the T cell capacity to respond to antigen and facilitates virus replication. HIV-1 infection subverts the formation and function of the immunological synapse altering both actin cytoskeleton remodeling and intracellular vesicle traffic. We describe here our methods to unveil how HIV-1 and in particular its protein Nef modify vesicle traffic to the immunological synapse, perturbing the synapse activation capacity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28179536/hiv-aids-vaccine-candidates-based-on-replication-competent-recombinant-poxvirus-nyvac-c-kc-expressing-trimeric-gp140-and-gag-derived-virus-like-particles-or-lacking-the-viral-molecule-b19-that-inhibits-type-i-interferon-activate-relevant-hiv-1-specific-b-and
#18
Juan García-Arriaza, Beatriz Perdiguero, Jonathan L Heeney, Michael S Seaman, David C Montefiori, Nicole L Yates, Georgia D Tomaras, Guido Ferrari, Kathryn E Foulds, Mario Roederer, Steven G Self, Bhavesh Borate, Raphael Gottardo, Sanjay Phogat, Jim Tartaglia, Susan W Barnett, Brian Burke, Anthony D Cristillo, Deborah E Weiss, Carter Lee, Karen V Kibler, Bertram L Jacobs, Ralf Wagner, Song Ding, Giuseppe Pantaleo, Mariano Esteban
The nonreplicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120) and Gag-Pol-Nef antigens (NYVAC-C) showed limited immunogenicity in phase I clinical trials. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4(+) and CD8(+) T cells, here we compared the HIV-1-specific immunogenicity elicited in nonhuman primates immunized with two replicating NYVAC vectors that have been modified by the insertion of the K1L and C7L vaccinia virus host range genes and express the clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC)...
May 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28179429/serinc5-protein-inhibits-hiv-1-fusion-pore-formation-by-promoting-functional-inactivation-of-envelope-glycoproteins
#19
Chetan Sood, Mariana Marin, Ajit Chande, Massimo Pizzato, Gregory B Melikyan
The host proteins, SERINC3 and SERINC5, have been recently shown to incorporate into HIV-1 particles and compromise their ability to fuse with target cells, an effect that is antagonized by the viral Nef protein. Envelope (Env) glycoproteins from different HIV-1 isolates exhibit a broad range of sensitivity to SERINC-mediated restriction, and the mechanism by which SERINCs interfere with HIV-1 fusion remains unclear. Here, we show that incorporation of SERINC5 into virions in the absence of Nef inhibits the formation of small fusion pores between viruses and cells...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28139864/role-of-autophagy-in-hiv-infection-and-pathogenesis
#20
R Nardacci, F Ciccosanti, C Marsella, G Ippolito, M Piacentini, G M Fimia
The aim of autophagy is to re-establish homeostasis in response to a variety of stress conditions. By forming double-membrane vesicles, autophagy engulfs damaged or superfluous cytoplasmic material and recycles degradation products for new synthesis or energy production. Of note, the same mechanism is used to capture pathogens and has important implications in both innate and adaptive immunity. To establish a chronic infection, pathogens have therefore evolved multiple mechanisms to evade autophagy-mediated degradation...
May 2017: Journal of Internal Medicine
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