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https://www.readbyqxmd.com/read/28916807/envelope-glycoprotein-mobility-on-hiv-1-particles-depends-on-the-virus-maturation-state
#1
Jakub Chojnacki, Dominic Waithe, Pablo Carravilla, Nerea Huarte, Silvia Galiani, Jörg Enderlein, Christian Eggeling
Human immunodeficiency virus type 1 (HIV-1) assembles as immature particles, which require the proteolytic cleavage of structural polyprotein Gag and the clustering of envelope glycoprotein Env for infectivity. The details of mechanisms underlying Env clustering remain unknown. Here, we determine molecular dynamics of Env on the surface of individual HIV-1 particles using scanning fluorescence correlation spectroscopy on a super-resolution STED microscope. We find that Env undergoes a maturation-induced increase in mobility, highlighting diffusion as one cause for Env clustering...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28916320/exosomes-carring-gag-env-of-alv-j-possess-negative-effect-on-immunocytes
#2
Guihua Wang, Zhenzhen Wang, Pingping Zhuang, Xiaomin Zhao, Ziqiang Cheng
J subgroup avian leukosis virus (ALV-J) is an exogenous retrovirus of avian. A key feature of ALV-J infection is leading to severe immunosuppressive characteristic of diseases. Viral components of retrovirus were reported closely associated with immunosuppression, and several similarities between exosomes and retrovirus preparations have lead to the hypotheses of retrovirus hijacker exosomes pathway. In this study, we purified exosomes from DF-1 cells infected and uninfected by ALV-J. Electron microscopy and mass spectrometry (MS) analysis showed that ALV-J not only increased the production of exosomes from ALV-J infected DF-1 cells (Exo-J) but also stimulated some proteins expression, especially ALV-J components secreted in exosomes...
September 12, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28915040/elucidating-the-interdependence-of-drug-resistance-from-combinations-of-mutations
#3
Debra A Ragland, Troy W Whitfield, Sook-Kyung Lee, Ronald Swanstrom, Konstantin B Zeldovich, Nese Kurt Yilmaz, Celia A Schiffer
HIV-1 protease is responsible for the cleavage of 12 non-homologous sites within the Gag and Gag-Pro-Pol polyproteins in the viral genome. Under the selective pressure of protease inhibition, the virus evolves mutations within (primary) and outside of (secondary) the active site allowing the protease to process substrates while simultaneously countering inhibition. The primary protease mutations impede inhibitor binding directly, while the secondary mutations are considered accessory mutations that compensate for a loss in fitness...
September 15, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28911033/formulation-of-chitosan-with-the-polyepitope-hiv-1-protein-candidate-vaccine-efficiently-boosts-cellular-immune-responses-in-mice
#4
Ehsan Ollah Jazaeri, Atiyeh Mahdavi, Asghar Abdoli
Human immunodeficiency virus-1 (HIV-1) continues to be a major global public health issue and priority. Despite the variety of antiretroviral therapies, it seems that an effective vaccine against HIV-1 is still very necessary. An ideal HIV-1 vaccine should be able to elicit both humoral and cellular immunities. In this respect, polyepitope vaccines, incorporated from several conserved regions of HIV-1 proteins, have received much attention recently. Herein, the immunogenicity of the HIV-1 polyepitope protein-based candidate vaccines was evaluated in BALB/c mice...
November 30, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28901284/correction-n-6-methyladenosine-of-hiv-1-rna-regulates-viral-infection-and-hiv-1-gag-protein-expression
#5
Nagaraja Tirumuru, Boxuan Simen Zhao, Wuxun Lu, Zhike Lu, Chuan He, Li Wu
No abstract text is available yet for this article.
September 13, 2017: ELife
https://www.readbyqxmd.com/read/28893281/rna-flow-cytometric-fish-for-investigations-into-hiv-immunology-vaccination-and-cure-strategies
#6
REVIEW
Amy E Baxter, Julia Niessl, Antigoni Morou, Daniel E Kaufmann
Despite the tremendous success of anti-retroviral therapy (ART) no current treatment can eradicate latent HIV reservoirs from HIV-infected individuals or generate, effective HIV-specific immunity. Technological limitations have hampered the identification and characterization of both HIV-infected cells and HIV-specific responses in clinical samples directly ex vivo. RNA-flow cytometric fluorescence in situ hybridisation (RNA Flow-FISH) is a powerful technique, which enables detection of mRNAs in conjunction with proteins at a single-cell level...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28884441/inhibition-of-retroviral-gag-assembly-by-non-silencing-mirnas-promotes-autophagic-viral-degradation
#7
Na Qu, Zhao Ma, Mengrao Zhang, Muaz N Rushdi, Christopher J Krueger, Antony K Chen
We recently reported an unconventional mechanism by which miRNAs inhibit HIV-1 viral production. This occurs when miRNAs bind nonspecifically to the viral structural protein Gag, interfering with viral RNA-mediated Gag assembly at the plasma membrane. Consequently, misassembled viral complexes are redirected into the endocytic pathway where they are delivered to lysosomes for degradation. In this study, we demonstrate that autophagy is a critical mediator of the viral degradation pathway and that this pathway is not HIV-1 specific...
September 7, 2017: Protein & Cell
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
#8
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/28880280/multiparametric-characterization-of-rare-hiv-infected-cells-using-an-rna-flow-fish-technique
#9
Amy E Baxter, Julia Niessl, Rémi Fromentin, Jonathan Richard, Filippos Porichis, Marta Massanella, Nathalie Brassard, Nirmin Alsahafi, Jean-Pierre Routy, Andrés Finzi, Nicolas Chomont, Daniel E Kaufmann
Efforts to cure HIV are hampered by limited characterization of the cells supporting HIV replication in vivo and inadequate methods for quantifying the latent viral reservoir in individuals receiving antiretroviral therapy (ART). We describe a protocol for flow cytometric identification of viral reservoirs, based on concurrent detection of cellular HIV Gagpol mRNA by in situ RNA hybridization combined with antibody staining for the HIV Gag protein. By simultaneously detecting both HIV RNA and protein, the CD4 T cells harboring translation-competent virus can be identified...
October 2017: Nature Protocols
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
#10
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/28878089/hla-b-14-02-restricted-env-specific-cd8-t-cell-activity-has-highly-potent-antiviral-efficacy-associated-with-immune-control-of-hiv-infection
#11
Ellen M Leitman, Christian B Willberg, Ming-Han Tsai, Huabiao Chen, Søren Buus, Fabian Chen, Lynn Riddell, David Haas, Jacques Fellay, James J Goedert, Alicja Piechocka-Trocha, Bruce D Walker, Jeffrey Martin, Steven Deeks, Steven M Wolinsky, Jeremy Martinson, Maureen Martin, Ying Qi, Asier Sáez-Cirión, Otto O Yang, Philippa C Matthews, Mary Carrington, Philip J R Goulder
Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8+ T-cell responses. We here focus on HLA-B*14, that protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response is Env-specific (ERYLKDQQL, 'HLA-B*14-EL9'). A subdominant HLA-B*14-restricted response targets Gag (DRYFKTLRA, 'HLA-B*14-DA9'). Using HLA-B*14/peptide-saporin conjugated tetramers, we show that HLA-B*14-EL9 is substantially more potent at inhibiting viral replication than HLA-B*14-DA9...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28873410/n-terminally-truncated-pom121c-inhibits-hiv-1-replication
#12
Hideki Saito, Hiroaki Takeuchi, Takao Masuda, Takeshi Noda, Shoji Yamaoka
Recent studies have identified host cell factors that regulate early stages of HIV-1 infection including viral cDNA synthesis and orientation of the HIV-1 capsid (CA) core toward the nuclear envelope, but it remains unclear how viral DNA is imported through the nuclear pore and guided to the host chromosomal DNA. Here, we demonstrate that N-terminally truncated POM121C, a component of the nuclear pore complex, blocks HIV-1 infection. This truncated protein is predominantly localized in the cytoplasm, does not bind to CA, does not affect viral cDNA synthesis, reduces the formation of 2-LTR and diminished the amount of integrated proviral DNA...
2017: PloS One
https://www.readbyqxmd.com/read/28851629/immunogenicity-of-virus-like-semliki-forest-virus-replicon-particles-expressing-indian-hiv-1c-gag-env-and-polrt-genes
#13
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/28847064/-hiv-subtype-in-newly-reported-hiv-infected-cases-in-dehong-prefecture-of-yunnan-province-2015
#14
X Duan, K R Wang, J B Wang, T Yang, Y K Wang, J Yang, R H Ye, Y C Yang, S T Yao, S Duan, N He
Objective: To explore the distribution of HIV subtype in newly detected people living with HIV from January to November, 2015 in Dehong Dai and Jingpo Autonomous Prefecture, Yunnan province. Methods: DNA extraction, reverse transcription polymerase chain reaction (RT-PCR) for gag, env, and pol amplification and amplification product sequencing were conducted by using plasmas of newly detected HIV-infected persons. The subtypes were confirmed by analyzing the sequences of 3 genes. Results: A total of 963 HIV infection cases were reported during this period, the HIV subtype was confirmed in 499 cases...
August 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28846854/conformations-of-the-hiv-1-protease-a-crystal-structure-data-set-analysis
#15
Luigi Leonardo Palese
The HIV protease is an important drug target for HIV/AIDS therapy, and its structure and function have been extensively investigated. This enzyme performs an essential role in viral maturation by processing specific cleavage sites in the Gag and Gag-Pol precursor polyproteins so as to release their mature forms. This 99 amino acid aspartic protease works as a homodimer, with the active site localized in a central cavity capped by two flexible flap regions. The dimer presents closed or open conformations, which are involved in the substrate binding and release...
August 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28843384/staging-of-recent-hiv-1-infection-using-geenius-rapid-confirmatory-assay-compared-to-inno-lia-new-lav-and-blot-2-2-assays
#16
E Tuaillon, A Sanosyan, A Pisoni, J Liscouët, A Makinson, P Van de Perre
BACKGROUND: Besides confirmation of HIV seropositivity, Western Blot (WB) assays play an important role for identification of recent infection based on incomplete antibody reactivity and lack of p31 band. OBJECTIVES: We evaluated the capacities of the Geenius™ HIV1/2 Confirmatory Assay (Bio-Rad), a new generation rapid confirmatory assay based on immune-chromatography and automated reading, for staging of HIV-1 infection. STUDY DESIGN: Sixteen samples collected during early HIV-1 infections (Fiebig stage III-VI) were tested using the Geenius assay, and compared to HIV Blot 2...
August 18, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28837706/a-dna-inducing-vlp-vaccine-designed-for-hiv-and-tested-in-mice
#17
Alexandre Calazans, Cesar Boggiano, Ross Lindsay
We developed a DNA vaccine that induces the formation of a VLP in vivo. This VLP was designed to elicit neutralizing antibodies, to induce better T-cell responses and to activate the innate immune system. Overall, 5 groups of 10 mice were electroporated with the following constructs: pVLP-LTR-GagPro [full], pVLP-GagPro [VLP wihout RNA], pVLP-LTR-Gag [VLP immature], pVLP-Gag and pVLP-EnvBG505 [regular DNA vaccine] and a mock group. We performed ICS on the mouse spleens and performed ELISA for ENV antibodies and a Luminex assay for inflammatory cytokines...
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
#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/28830571/anti-herv-k-hml-2-capsid-antibody-responses-in-hiv-elite-controllers
#19
Miguel de Mulder, Devi SenGupta, Steven G Deeks, Jeffrey N Martin, Christopher D Pilcher, Frederick M Hecht, Jonah B Sacha, Douglas F Nixon, Henri-Alexandre Michaud
BACKGROUND: Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection. RESULTS: We developed an ELISA assay using either recombinant protein or 164 redundant "15mer" HERV-K (HML-2) Gag peptides to test sera for antibody reactivity...
August 22, 2017: Retrovirology
https://www.readbyqxmd.com/read/28827668/a-clue-to-unprecedented-strategy-to-hiv-eradication-lock-in-and-apoptosis
#20
Hiroshi Tateishi, Kazuaki Monde, Kensaku Anraku, Ryoko Koga, Yuya Hayashi, Halil Ibrahim Ciftci, Hasan DeMirci, Taishi Higashi, Keiichi Motoyama, Hidetoshi Arima, Masami Otsuka, Mikako Fujita
Despite the development of antiretroviral therapy against HIV, eradication of the virus from the body, as a means to a cure, remains in progress. A "kick and kill" strategy proposes "kick" of the latent HIV to an active HIV to eventually be "killed". Latency-reverting agents that can perform the "kick" function are under development and have shown promise. Management of the infected cells not to produce virions after the "kick" step is important to this strategy. Here we show that a newly synthesized compound, L-HIPPO, captures the HIV-1 protein Pr55(Gag) and intercepts its function to translocate the virus from the cytoplasm to the plasma membrane leading to virion budding...
August 21, 2017: Scientific Reports
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