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https://www.readbyqxmd.com/read/28819214/hiv-1-nef-induced-cardiotoxicity-through-dysregulation-of-autophagy
#1
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
#2
Chen Wang, Yan Wang, Desheng Kong, Ruolei Xin, Weisi Xu, Yi Feng, Yiming Shao, Liying Ma
Co-circulation of multiple subtypes in same population contributes significantly to the emergence of recombinant viruses. BJ2015EU19, a novel CCR5-tropic HIV-1 second-generation recombinant virus,was isolated from a man who has sex with man in Beijing, China. Phylogenetic analysis of the near full-length genome showed that BJ2015EU19 was 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...
August 10, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28771107/hla-dqb1-06-and-breadth-of-nef-core-region-specific-t-cell-response-are-associated-with-slow-disease-progression-in-antiretroviral-therapy-naive-chinese-hiv-1-subtype-b-patients
#3
Weihua Li, Chuanyun Li, Wei Xia, Xiuhui Li
Vaccines still are an important way to prevent and treat acquired immunodeficiency syndrome (AIDS). (1) For developing an effective T cell-based AIDS vaccine, it is critical to define the human leukocyte antigen (HLA) type and epitope that elicit the most potent responses. This study involved 29 antiretroviral therapy-naive and chronic human immunodeficiency virus (HIV)-1 subtype B-infected individuals. A polymerase chain reaction-sequence-specific primer was used to detect the HLA typing, and the enzyme-linked immunospot assay to quantify the T-cell immune function...
August 3, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28762184/nef-is-secreted-in-exosomes-from-nef-gfp-expressing-and-hiv-1-infected-human-astrocytes
#4
Pia Pužar Dominkuš, Jana Ferdin, Ana Plemenitaš, Boris Matija Peterlin, Metka Lenassi
HIV-1 infection of the central nervous system causes HIV-associated neurocognitive disorders, even in aviremic patients. Although astrocyte malfunction was associated to these disorders, their implication is overshadowed by contributions of microglia and macrophages. Astrocytes are infected with HIV-1 in vivo and express a relevant amount of viral protein Nef. Nef was shown to stimulate its own release in exosomes from diverse cell types, which in turn have damaging effects on neighboring cells. Using immunoblotting and electron microscopy, we showed that human astrocytes expressing Nef...
July 31, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28750321/modeling-the-evolution-of-siv-sooty-mangabey-progenitor-virus-towards-hiv-2-using-humanized-mice
#5
Kimberly Schmitt, Dipu Mohan Kumar, James Curlin, Leila Remling-Mulder, Mark Stenglein, Shelby O'Connor, Preston Marx, Ramesh Akkina
HIV-2 is thought to have originated from an SIV progenitor native to sooty mangabeys. To model the initial human transmission and understand the sequential viral evolution, humanized mice were infected with SIVsm and serially passaged for five generations. Productive infection was seen by week 3 during the initial challenge followed by chronic viremia and gradual CD4(+) T cell decline. Viral loads increased by the 5th generation resulting in more rapid CD4(+) T cell decline. Genetic analysis revealed several amino acid substitutions that were nonsynonymous and fixed in multiple hu-mice across each of the 5 generations in the nef, env and rev regions...
July 24, 2017: Virology
https://www.readbyqxmd.com/read/28743825/contribution-of-the-clathrin-adaptor-ap-1-subunit-%C3%A2%C2%B51-to-acidic-cluster-protein-sorting
#6
Paloma Navarro Negredo, James R Edgar, Antoni G Wrobel, Nathan R Zaccai, Robin Antrobus, David J Owen, Margaret S Robinson
Acidic clusters act as sorting signals for packaging cargo into clathrin-coated vesicles (CCVs), and also facilitate down-regulation of MHC-I by HIV-1 Nef. To find acidic cluster sorting machinery, we performed a gene-trap screen and identified the medium subunit (µ1) of the clathrin adaptor AP-1 as a top hit. In µ1 knockout cells, intracellular CCVs still form, but acidic cluster proteins are depleted, although several other CCV components were either unaffected or increased, indicating that cells can compensate for long-term loss of AP-1...
July 25, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28732035/vaccine-induced-immune-responses-against-both-gag-and-env-improve-control-of-simian-immunodeficiency-virus-replication-in-rectally-challenged-rhesus-macaques
#7
Mauricio A Martins, Young C Shin, Lucas Gonzalez-Nieto, Aline Domingues, Martin J Gutman, Helen S Maxwell, Iris Castro, Diogo M Magnani, Michael Ricciardi, Nuria Pedreño-Lopez, Varian Bailey, Dillon Betancourt, John D Altman, Matthias Pauthner, Dennis R Burton, Benjamin von Bredow, David T Evans, Maoli Yuan, Christopher L Parks, Keisuke Ejima, David B Allison, Eva Rakasz, Glen N Barber, Saverio Capuano, Jeffrey D Lifson, Ronald C Desrosiers, David I Watkins
The ability to control lentivirus replication may be determined, in part, by the extent to which individual viral proteins are targeted by the immune system. Consequently, defining the antigens that elicit the most protective immune responses may facilitate the design of effective HIV-1 vaccines. Here we vaccinated four groups of rhesus macaques with a heterologous vector prime/boost/boost/boost (PBBB) regimen expressing the following simian immunodeficiency virus (SIV) genes: env, gag, vif, rev, tat, and nef (Group 1); env, vif, rev, tat, and nef (Group 2); gag, vif, rev, tat, and nef (Group 3); or vif, rev, tat, and nef (Group 4)...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28729737/direct-binding-to-gabarap-family-members-is-essential-for-hiv-1-nef-plasma-membrane-localization
#8
Alexandra Boeske, Melanie Schwarten, Peixiang Ma, Markus Tusche, Jessica Mötter, Christina Möller, Philipp Neudecker, Silke Hoffmann, Dieter Willbold
HIV-1 Nef is an important pathogenic factor for HIV/AIDS pathogenesis. Studies have shown that the association of Nef with the inner leaflet of the plasma membrane and with endocytic and perinuclear vesicles is essential for most activities of Nef. Using purified recombinant proteins in pull-down assays and by co-immunoprecipitation assays we demonstrate that Nef binds directly and specifically to all GABARAP family members, but not to LC3 family members. Based on nuclear magnetic resonance (NMR) experiments we showed that Nef binds to GABARAP via two surface exposed hydrophobic pockets...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28712312/near-full-length-genome-sequence-of-a-novel-hiv-1-second-generation-recombinant-form-crf01_ae-crf07_bc-detected-among-blood-donors-in-north-china
#9
Wei He, Xiaoxu Han, Minghui An, Yanqiu Hai, Le Chang, Chao Liu, Lunan Wang, Hong Shang
In this study, a novel CRF01_AE/07_BC HIV-1 recombinant form, with five breakpoints in the pol, vpr, env, and nef gene regions, was identified from a voluntary blood donor in North China. Our study showed that this HIV-1 recombinant form might be a second-generation recombinant form from two predominant strains in the men who have sex with men (MSM) population, with the CRF07_BC fragments belonging to a CRF07_BC lineage specific to Chinese MSM and the CRF01_AE fragments belonging to the CRF01_AE lineage 5 common among MSM in northern China...
August 16, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28681118/naturally-occurring-vpr-inhibitors-from-medicinal-plants-of-myanmar
#10
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/28664742/delivery-of-hiv-1-nef-linked-to-heat-shock-protein-27-using-a-cationic-polymer-is-more-effective-than-cationic-lipid-in-mammalian-cells
#11
A Milani, A Bolhassani, M Heshmati
BACKGROUND: Different adjuvants and delivery systems have been used to enhance the potency of DNA vaccines against viral diseases. Among them, heat shock proteins (HSPs) are stress proteins that have multiple roles such as chaperon activity and anti-apoptotic and adjuvant properties. The goal of this study was to compare the expression of HIV-1 Nef, Hsp27 and Hsp27-Nef genes transfected in HEK-293T mammalian cells by TurboFect and Lipofectamine as a cationic polymer and lipid, respectively...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28659343/the-host-cell-restriction-factor-serinc5-restricts-hiv-1-infectivity-without-altering-the-lipid-composition-and-organization-of-viral-particles
#12
Birthe Trautz, Hannah Wiedemann, Christian L Uumlchtenborg, Virginia Pierini, Jan Kranich, B Aumlrbel Glass, Hans-Georg Kr Aumlusslich, Thomas Brocker, Massimo Pizzato, Alessia Ruggieri, Britta Br Uumlgger, Oliver T Fackler
The host-cell restriction factor SERINC5 potently suppresses the infectivity of HIV-1 particles and is counteracted by the viral pathogenesis factor Nef. However, the molecular mechanism by which SERINC5 restricts HIV-1 particle infectivity is still unclear. Since SERINC proteins have been suggested to facilitate the incorporation of serine during the biosynthesis of membrane lipids and because lipid composition of HIV particles is a major determinant of the particles infectious potential, we tested whether SERINC5-mediated restriction of HIV particle infectivity involves alterations of membrane lipid composition...
June 28, 2017: Journal of Biological Chemistry
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
#13
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-proteins-from-elite-controllers-sensitizes-hiv-1-infected-cells-to-antibody-dependent-cellular-cytotoxicity
#14
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...
August 15, 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
#15
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...
August 2017: Immunology Letters
https://www.readbyqxmd.com/read/28586246/characterization-of-a-new-hiv-1-crf01_ae-crf07_bc-recombinant-virus-in-guangxi-china
#16
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
#17
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...
September 2017: Virology
https://www.readbyqxmd.com/read/28574482/immunologic-and-virologic-mechanisms-for-partial-protection-from-intravenous-challenge-by-an-integration-defective-siv-vaccine
#18
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
#19
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
#20
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
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