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HIV nef

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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
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/28968792/control-of-hiv-1-by-an-hla-b-52-01-c-12-02-protective-haplotype
#4
Takayuki Chikata, Hayato Murakoshi, Madoka Koyanagi, Kazutaka Honda, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi
HLA-B*52:01-C*12:02, which is found in approximately 20 % of all Japanese, is well known to be associated with ulcerative colitis and Takayasu arteritis. This haplotype is also known to be a protective one in HIV-1-infective individuals. Recent studies showed that HLA-B*52:01-restricted HIV-1-specific T cells suppress HIV-1 and that HLA-C*12:02 together with KIR2DL2 play an important role in NK cell-mediated control of HIV-1. However, the role of HLA-C*12:02-restricted CTLs in suppression of HIV-1 replication remains unknown...
September 14, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28961413/making-sense-of-multifunctional-proteins-human-immunodeficiency-virus-type-1-accessory-and-regulatory-proteins-and-connections-to-transcription
#5
Tyler B Faust, Jennifer M Binning, John D Gross, Alan D Frankel
Viruses are completely dependent upon cellular machinery to support replication and have therefore developed strategies to co-opt cellular processes to optimize infection and counter host immune defenses. Many viruses, including human immunodeficiency virus type 1 (HIV-1), encode a relatively small number of genes. Viruses with limited genetic content often encode multifunctional proteins that function at multiple stages of the viral replication cycle. In this review, we discuss the functions of HIV-1 regulatory (Tat and Rev) and accessory (Vif, Vpr, Vpu, and Nef) proteins...
September 29, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28951475/mutations-located-outside-the-integrase-gene-can-confer-resistance-to-hiv-1-integrase-strand-transfer-inhibitors
#6
Isabelle Malet, Frédéric Subra, Charlotte Charpentier, Gilles Collin, Diane Descamps, Vincent Calvez, Anne-Geneviève Marcelin, Olivier Delelis
Resistance to the integrase strand transfer inhibitors raltegravir and elvitegravir is often due to well-identified mutations in the integrase gene. However, the situation is less clear for patients who fail dolutegravir treatment. Furthermore, most in vitro experiments to select resistance to dolutegravir have resulted in few mutations of the integrase gene. We performed an in vitro dolutegravir resistance selection experiment by using a breakthrough method. First, MT4 cells were infected with human immunodeficiency virus type 1 (HIV-1) Lai...
September 26, 2017: MBio
https://www.readbyqxmd.com/read/28946621/canonical-and-non-canonical-autophagy-in-hiv-1-replication-cycle
#7
REVIEW
Olivier Leymarie, Leslie Lepont, Clarisse Berlioz-Torrent
Autophagy is a lysosomal-dependent degradative process essential for maintaining cellular homeostasis, and is a key player in innate and adaptive immune responses to intracellular pathogens such as human immunodeficiency virus type 1 (HIV-1). In HIV-1 target cells, autophagy mechanisms can (i) selectively direct viral proteins and viruses for degradation; (ii) participate in the processing and presentation of viral-derived antigens through major histocompatibility complexes; and (iii) contribute to interferon production in response to HIV-1 infection...
September 23, 2017: Viruses
https://www.readbyqxmd.com/read/28931520/dna-priming-increases-frequency-of-t-cell-responses-to-a-vsv-hiv-vaccine-with-specific-enhancement-of-cd8-t-cell-responses-by-il-12-pdna
#8
Shuying S Li, Nidhi K Kochar, Marnie Elizaga, Christine M Hay, Gregory J Wilson, Kristen W Cohen, Stephen C De Rosa, Rong Xu, Ayuko Ota-Setlik, Daryl Morris, Greg Finak, Mary Allen, Hong-Van Tieu, Ian Frank, Magdalena E Sobieszczyk, Drew Hannaman, Raphael Gottardo, Peter B Gilbert, Georgia D Tomaras, Lawrence Corey, David K Clarke, Michael A Egan, John H Eldridge, M Juliana McElrath, Nicole Frahm
HVTN 087 assessed the effect of increasing doses of pIL-12 adjuvant on the immunogenicity of a HIV-1 multi-antigen (MAG) DNA vaccine delivered by electroporation and boosted with an attenuated VSV-Gag vaccine. We randomized 100 healthy adults to receive placebo, or 3mg HIV-MAG (gag/pol, env, nef/tat/vif) DNA vaccine co-administered with pIL-12 at 0μg, 250μg, 1,000μg or 1,500μg intramuscularly by electroporation at 0, 1 and 3 months followed by intramuscular inoculation with 3.4×10(7) PFU VSV-Gag vaccine at 6 months...
September 20, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28931091/t-cell-responses-targeting-hiv-nef-uniquely-correlate-with-infected-cell-frequencies-after-long-term-antiretroviral-therapy
#9
Allison S Thomas, Kimberley L Jones, Rajesh T Gandhi, Deborah K McMahon, Joshua C Cyktor, Dora Chan, Szu-Han Huang, Ronald Truong, Alberto Bosque, Amanda B Macedo, Colin Kovacs, Erika Benko, Joseph J Eron, Ronald J Bosch, Christina M Lalama, Samuel Simmens, Bruce D Walker, John W Mellors, R Brad Jones
HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART), these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28917624/small-heat-shock-protein-27-an-effective-adjuvant-for-enhancement-of-hiv-1-nef-antigen-specific-immunity
#10
Alireza Milani, Azam Bolhassani, Sepideh Shahbazi, Fatemeh Motevalli, Seyed Mehdi Sadat, Sepehr Soleymani
Novel vaccine modalities have been designed to improve the efficiency of vaccines against HIV infections. In this way, the HIV-1 Nef protein has been known as an attractive antigenic candidate in therapeutic vaccine development. Moreover, the endogenous adjuvants such as heat shock proteins (HSPs) and high mobility group box 1 protein (HMGB1) have been suggested effectively to induce antigen-specific humoral and cellular immune responses. In this study, different Nef DNA and protein constructs were produced in eukaryotic and prokaryotic expression systems, and their immunostimulatory properties were evaluated using small heat shock protein 27 (Hsp27) and the HMGB1-derived peptide (Hp91) in a mouse model...
September 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28893294/hiv-i-nef-inhibitors-a-novel-class-of-hiv-specific-immune-adjuvants-in-support-of-a-cure
#11
REVIEW
Gregory A Dekaban, Jimmy D Dikeakos
The success of many current vaccines relies on a formulation that incorporates an immune activating adjuvant. This will hold true for the design of a successful therapeutic HIV vaccine targeted at controlling reactivated virus following cessation of combined antiretroviral therapy (cART). The HIV accessory protein Nef functions by interfering with HIV antigen presentation through the major histocompatibility complex I (MHC-I) pathway thereby suppressing CD8(+) cytotoxic T cell (CTL)-mediated killing of HIV infected cells...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28893272/killed-whole-hiv-vaccine-employing-a-well-established-strategy-for-antiviral-vaccines
#12
REVIEW
C Yong Kang, Yong Gao
The development of an efficient prophylactic HIV vaccine has been one of the major challenges in infectious disease research during the last three decades. Here, we present a mini review on strategies employed for the development of HIV vaccines with an emphasis on a well-established vaccine technology, the killed whole-virus vaccine approach. Recently, we reported an evaluation of the safety and the immunogenicity of a genetically modified and killed whole-HIV-1 vaccine designated as SAV001 [1]. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence of the Env signal peptide with that of honeybee melittin to produce an avirulent and replication efficient HIV-1...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28885709/prenylation-of-viral-proteins-by-enzymes-of-the-host-virus-driven-rationale-for-therapy-with-statins-and-ft-ggt1-inhibitors
#13
REVIEW
Ekaterina S Marakasova, Birgit Eisenhaber, Sebastian Maurer-Stroh, Frank Eisenhaber, Ancha Baranova
Intracellular bacteria were recently shown to employ eukaryotic prenylation system for modifying activity and ensuring proper intracellular localization of their own proteins. Following the same logic, the proteins of viruses may also serve as prenylation substrates. Using extensively validated high-confidence prenylation predictions by PrePS with a cut-off for experimentally confirmed farnesylation of hepatitis delta virus antigen, we compiled in silico evidence for several new prenylation candidates, including IRL9 (CMV) and few other proteins encoded by Herpesviridae, Nef (HIV-1), E1A (human adenovirus 1), NS5A (HCV), PB2 (influenza), HN (human parainfluenza virus 3), L83L (African swine fever), MC155R (molluscum contagiosum virus), other Poxviridae proteins, and some bacteriophages of human associated bacteria...
September 8, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28882621/antibodies-targeting-btla-or-tim-3-enhance-hiv-1-specific-t-cell-responses-in-combination-with-pd-1-blockade
#14
Katharina Grabmeier-Pfistershammer, Carmen Stecher, Markus Zettl, Sandra Rosskopf, Armin Rieger, Gerhard J Zlabinger, Peter Steinberger
Persistent stimulation with antigens derived from viruses that establish chronic infections or tumour antigens results in the exhaustion of T cells. Coinhibitory receptors like PD-1 and CTLA-4 function as immune checkpoints on exhausted T cells. Blocking these molecules with antibodies improve immunity to cancer cells. Immune checkpoint inhibitors targeting other coinhibitory receptors might have a similar role in improving T cell function and thus also utility in cancer therapy. Using HIV-specific T cells as a model for exhaustion we have evaluated the capacity of antibodies targeting TIM-3, BTLA, CD160, LAG-3 and CTLA-4 alone or in combination with a PD-1 antibody to enhance proliferation and cytokine production in response to Gag and Nef peptides...
September 4, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28878119/pharmacologic-hiv-1-nef-blockade-promotes-cd8-t-cell-mediated-elimination-of-latently-hiv-1-infected-cells-in-vitro
#15
Shariq Mujib, Aamir Saiyed, Saleh Fadel, Ardalan Bozorgzad, Nasra Aidarus, Feng Yun Yue, Erika Benko, Colin Kovacs, Lori A Emert-Sedlak, Thomas E Smithgall, Mario A Ostrowski
Eradication of the HIV-1 latent reservoir represents the current paradigm to developing a cure for AIDS. HIV-1 has evolved multiple mechanisms to evade CD8 T cell responses, including HIV-1 Nef-mediated downregulation of MHC-I from the surface of infected cells. Nef transcripts and protein are detectable in samples from aviremic donors, suggesting that Nef expression in latently HIV-1-infected CD4 T cells protects them from immune-mediated clearance. Here, we tested 4 small molecule inhibitors of HIV-1 Nef in an in vitro primary CD4 T cell latency model and measured the ability of autologous ex vivo or HIV-1 peptide-expanded CD8 T cells to recognize and kill latently infected cells as a function of inhibitor treatment...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28874665/endocytic-sorting-motif-interactions-involved-in-nef-mediated-downmodulation-of-cd4-and-cd3
#16
Santiago Manrique, Daniel Sauter, Florian A Horenkamp, Sebastian Lülf, Hangxing Yu, Dominik Hotter, Kanchan Anand, Frank Kirchhoff, Matthias Geyer
Lentiviral Nefs recruit assembly polypeptide complexes and target sorting motifs in cellular receptors to induce their internalization. While Nef-mediated CD4 downmodulation is conserved, the ability to internalize CD3 was lost in HIV-1 and its precursors. Although both functions play key roles in lentiviral replication and pathogenicity, the underlying structural requirements are poorly defined. Here, we determine the structure of SIVmac239 Nef bound to the ExxxLM motif of another Nef molecule at 2.5 Å resolution...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28859166/primate-lentiviruses-use-at-least-three-alternative-strategies-to-suppress-nf-%C3%AE%C2%BAb-mediated-immune-activation
#17
Dominik Hotter, Teresa Krabbe, Elisabeth Reith, Ali Gawanbacht, Nadia Rahm, Ahidjo Ayouba, Benoît Van Driessche, Carine Van Lint, Martine Peeters, Frank Kirchhoff, Daniel Sauter
Primate lentiviruses have evolved sophisticated strategies to suppress the immune response of their host species. For example, HIV-2 and most simian immunodeficiency viruses (SIVs) use their accessory protein Nef to prevent T cell activation and antiviral gene expression by downmodulating the T cell receptor CD3. This Nef function was lost in HIV-1 and other vpu-encoding viruses suggesting that the acquisition of Vpu-mediated NF-κB inhibition reduced the selection pressure for inhibition of T cell activation by Nef...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28832407/prevalence-and-clinical-impacts-of-hiv-1-intersubtype-recombinants-in-uganda-revealed-by-near-full-genome-population-and-deep-sequencing-approaches
#18
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/28819214/hiv-1-nef-induced-cardiotoxicity-through-dysregulation-of-autophagy
#19
Manish K Gupta, Rafal Kaminski, Brian Mullen, Jennifer Gordon, Tricia H Burdo, Joseph Y Cheung, Arthur M Feldman, Muniswamy Madesh, Kamel Khalili
Cardiovascular disease is a leading cause of co-morbidity in HIV-1 positive patients, even those in whom plasma virus levels are well-controlled. The pathogenic mechanism of HIV-1-associated cardiomyopathy is unknown, but has been presumed to be mediated indirectly, owing to the absence of productive HIV-1 replication in cardiomyocytes. We sought to investigate the effect of the HIV-1 auxiliary protein, Nef, which is suspected of extracellular release by infected CD4+ T cells on protein quality control and autophagy in cardiomyocytes...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28793783/characterization-of-a-novel-hiv-1-second-generation-recombinant-form-in-men-who-have-sex-with-men-in-beijing-china
#20
Chen Wang, Yan Wang, Desheng Kong, Ruolei Xin, Weisi Xu, Yi Feng, Yiming Shao, Liying Ma
Cocirculation of multiple subtypes in the same population contributes significantly to the emergence of recombinant viruses. BJ2015EU19, a novel CCR5-tropic human immunodeficiency virus (HIV)-1, second-generation recombinant virus, was isolated from a man who has sex with men in Beijing, China. Phylogenetic analysis of the near full-length genome showed that BJ2015EU19 consisted of seven fragments from CRF01_AE and CRF07_BC. There were six recombinant breakpoints in the pol, vpu, env, and nef genes of BJ2015EU19, which were different from the other circulating recombinant forms and unique recombinant forms (URFs)...
September 8, 2017: AIDS Research and Human Retroviruses
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