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https://www.readbyqxmd.com/read/28915327/adipose-tissue-in-hiv-infection
#1
John R Koethe
HIV infection and antiretroviral therapy (ART) treatment exert diverse effects on adipocytes and stromal-vascular fraction cells, leading to changes in adipose tissue quantity, distribution, and energy storage. A HIV-associated lipodystrophic condition was recognized early in the epidemic, characterized by clinically apparent changes in subcutaneous, visceral, and dorsocervical adipose depots. Underlying these changes is altered adipose tissue morphology and expression of genes central to adipocyte maturation, regulation, metabolism, and cytokine signaling...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28899754/on-the-whereabouts-of-hiv-1-cellular-entry-and-its-fusion-ports
#2
REVIEW
G Maria Jakobsdottir, Maro Iliopoulou, Rory Nolan, Luis Alvarez, Alex A Compton, Sergi Padilla-Parra
HIV-1 disseminates to diverse tissues through different cell types and establishes long-lived reservoirs. The exact cellular compartment where fusion occurs differs depending on the cell type and mode of viral transmission. This implies that HIV-1 may modulate a number of common host cell factors in different cell types. In this review, we evaluate recent advances on the host cell factors that play an important role in HIV-1 entry and fusion. New insights from restriction factors inhibiting virus-cell fusion in vitro may contribute to the development of future therapeutic interventions...
September 9, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28895059/central-nervous-system-penetrating-antiretrovirals-impair-energetic-reserve-in-striatal-nerve-terminals
#3
Kelly L Stauch, Katy Emanuel, Benjamin G Lamberty, Brenda Morsey, Howard S Fox
The use of antiretroviral (ARV) drugs with central nervous system (CNS) penetration effectiveness (CPE) may be useful in the treatment of HIV-associated neurocognitive disorder (HAND) as well as targeting a CNS reservoir in strategies to achieve a functional cure for HIV. However, increased cognitive deficits are linked to at least one of these drugs (efavirenz). As mitochondrial dysfunction has been found with a number of ARVs, and as such can affect neuronal function, the objective of this study was to assess the effects of ARV with high CPE for toxicological profiles on presynaptic nerve terminal energy metabolism...
September 11, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28894444/modeling-kick-kill-strategies-toward-hiv-cure
#4
REVIEW
Esteban A Hernandez-Vargas
Although combinatorial antiretroviral therapy (cART) potently suppresses the virus, a sterile or functional cure still remains one of the greatest therapeutic challenges worldwide. Reservoirs are infected cells that can maintain HIV persistence for several years in patients with optimal cART, which is a leading obstacle to eradicate the virus. Despite the significant progress that has been made in our understanding of the diversity of cells that promote HIV persistence, many aspects that are critical to the development of effective therapeutic approaches able to purge the latent CD4+ T cell reservoir are poorly understood...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28893281/rna-flow-cytometric-fish-for-investigations-into-hiv-immunology-vaccination-and-cure-strategies
#5
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/28893280/eradication-of-hiv-1-latent-reservoirs-through-therapeutic-vaccination
#6
REVIEW
Joshua Pankrac, Katja Klein, Jamie F S Mann
Despite the significant success of combination anti-retroviral therapy to reduce HIV viremia and save lives, HIV-1 infection remains a lifelong infection that must be appropriately managed. Advances in the understanding of the HIV infection process and insights from vaccine development in other biomedical fields such as cancer, imaging, and genetic engineering have fueled rapid advancements in HIV cure research. In the last few years, several studies have focused on the development of "Kick and Kill" therapies to reverse HIV latency and kick start viral translational activity...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28892313/-hiv-cure-a-realistic-perspective
#7
G Darcis, M Moutschen
More than 30 years after its discovery, human immunodeficiency virus (HIV) continues to be a major global public health issue. Antiretroviral therapy increases survival and quality of life of HIV-infected patients but is not curative. Indeed, interruption of therapy invariably leads to the re-emergence of detectable viral replication, since HIV persists in extremely long-lived viral latent reservoirs. Those viral latent reservoirs constitute the major source of viral recovery following antiretroviral treatment interruption and are considered as the most important hurdle to HIV eradication...
September 2017: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28890135/targeted-immune-interventions-for-an-hiv-1-cure
#8
REVIEW
Matthieu Perreau, Riddhima Banga, Giuseppe Pantaleo
Combination antiretroviral therapy (cART) induces durable suppression of virus replication but is unable to eradicate HIV. Invariably, virus rebound follows treatment interruption and life-long cART is thus required. Advances have been made in our understanding of HIV latency, identification of HIV cell reservoirs, regulation of HIV-specific immune responses, as well as in the development of broad neutralizing antibodies and putative therapeutic vaccines. These have provided a scientific basis to explore alternative strategies that achieve durable suppression of viremia in the absence of cART, the so-called functional cure...
September 7, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28887441/hiv-1-mediated-insertional-activation-of-stat5b-and-bach2-trigger-viral-reservoir-in-t-regulatory-cells
#9
Daniela Cesana, Francesca R Santoni de Sio, Laura Rudilosso, Pierangela Gallina, Andrea Calabria, Stefano Beretta, Ivan Merelli, Elena Bruzzesi, Laura Passerini, Silvia Nozza, Elisa Vicenzi, Guido Poli, Silvia Gregori, Giuseppe Tambussi, Eugenio Montini
HIV-1 insertions targeting BACH2 or MLK2 are enriched and persist for decades in hematopoietic cells from patients under combination antiretroviral therapy. However, it is unclear how these insertions provide such selective advantage to infected cell clones. Here, we show that in 30/87 (34%) patients under combination antiretroviral therapy, BACH2, and STAT5B are activated by insertions triggering the formation of mRNAs that contain viral sequences fused by splicing to their first protein-coding exon. These chimeric mRNAs, predicted to express full-length proteins, are enriched in T regulatory and T central memory cells, but not in other T lymphocyte subsets or monocytes...
September 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28884279/primary-hiv-infection-clinical-presentation-testing-and-treatment
#10
REVIEW
Aurélia Henn, Clara Flateau, Sébastien Gallien
PURPOSE OF REVIEW: The purpose of this review was to provide current data on clinical presentation, diagnosis, and treatment of primary HIV infection (PHI). RECENT FINDINGS: In 65 to 95% of cases, PHI causes acute retroviral syndrome presenting with unspecific flu-like symptoms. Symptomatic PHI was associated with a faster clinical and immunological progression of HIV infection. Point-of-care tests remain less sensitive than fourth-generation immunoassays (IA) in PHI, especially after tenofovir-based prophylaxis use...
September 7, 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28882067/differentiating-immune-cell-targets-in-gut-associated-lymphoid-tissue-for-hiv-cure
#11
Shahzada Khan, Sushama Telwatte, Martin Trapecar, Steven Yukl, Shomyseh Sanjabi
The single greatest challenge to an HIV cure is the persistence of latently-infected cells containing inducible, replication-competent proviral genomes that constitute only a small fraction of total or infected cells in the body. Although resting CD4+ T cells in the blood are a well-known source of viral rebound, more than 90% of the body's lymphocytes reside elsewhere. Many are in gut tissue, where HIV DNA levels per million CD4+ T cells are considerably higher than in the blood. Despite the significant contribution of gut tissue to viral replication and persistence, little is known about the cell types that support persistence of HIV in the gut; importantly, T cells in the gut have phenotypic, functional, and survival properties that are distinct from T cells in other tissues...
September 7, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28882052/an-optimized-and-validated-method-for-isolation-and-characterization-of-lymphocytes-from-hiv-human-gut-biopsies
#12
Martin Trapecar, Shahzada Khan, Nadia Roan, Tsui-Hua Chen, Sushama Telwatte, Monika Deswal, Montha Pao, Ma Somsouk, Steven G Deeks, Peter W Hunt, Steven Yukl, Shomyseh Sanjabi
The gastrointestinal (GI) tract harbors most of the body's immune cells and is also a major HIV reservoir in ART-treated patients. To achieve a cure, most HIV-infected cells must be identified and eliminated. While obtaining gut biopsies is a relatively non-invasive method of sampling relevant tissue for monitoring HIV activity, immune cell isolation from these limited tissue samples has proven to be challenging. Enzymatic tissue digestion is required for maximal immune cell isolation from gut biopsies. However, these enzymatic digestions can also be detrimental for preservation of cellular surface markers that are required for accurate identification of various subsets of leukocytes...
September 7, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28880280/multiparametric-characterization-of-rare-hiv-infected-cells-using-an-rna-flow-fish-technique
#13
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/28879788/development-of-an-epitope-based-hiv-1-vaccine-strategy-from-hiv-1-lipopeptide-to-dendritic-based-vaccines
#14
Mathieu Surenaud, Christine Lacabaratz, Gérard Zurawski, Yves Lévy, Jean-Daniel Lelièvre
Development of a safe, effective and globally affordable Human Immunodeficiency Virus strain 1 (HIV-1) vaccine offers the best hope for future control of the HIV-1 pandemic. However, with the exception of the recent RV144 trial, which elicited a modest level of protection against infection, no vaccine candidate has shown efficacy in preventing HIV-1 infection or in controlling virus replication in humans. There is also a great need for a successful immunotherapeutic vaccine since combination antiretroviral therapy (cART) does not eliminate the reservoir of HIV-infected cells...
September 7, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28879787/moving-forward-with-treatment-options-for-hiv-infected-children
#15
Jean-Christophe Beghin, Jean Cyr Yombi, Jean Ruelle, Dimitri Van der Linden
Current international guidelines recommend to treat all HIV-1 infected patients regardless of CD4 cell count. Despite the remarkable worldwide progress for universal access to antiretroviral during the last decade, the pediatric population remains fragile due to lack of randomized studies, inappropriate antiretroviral formulations, adherence difficulties, drug toxicity and development of resistance. Areas covered: This review summarizes the latest recommendations and advances for the treatment of HIV-infected children and highlights the potential complications of a lifelong antiretroviral treatment initiated early in life...
September 7, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28878233/a-chalcone-derivative-reactivates-latent-hiv-1-transcription-through-activating-p-tefb-and-promoting-tat-sec-interaction-on-viral-promoter
#16
Jun Wu, Ming-Tao Ao, Rui Shao, Hui-Ru Wang, Diao Yu, Mei-Juan Fang, Xiang Gao, Zhen Wu, Qiang Zhou, Yu-Hua Xue
The principal barrier to the eradication of HIV/AIDS is the existence of latent viral reservoirs. One strategy to overcome this barrier is to use latency-reversing agents (LRAs) to reactivate the latent proviruses, which can then be eliminated by effective anti-retroviral therapy. Although a number of LRAs have been found to reactivate latent HIV, they have not been used clinically due to high toxicity and poor efficacy. In this study, we report the identification of a chalcone analogue called Amt-87 that can significantly reactivate the transcription of latent HIV provirses and act synergistically with known LRAs such as prostratin and JQ1 to reverse latency...
September 6, 2017: Scientific Reports
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
#17
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
#18
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/28874382/evaluation-of-the-innate-immune-modulator-acitretin-as-a-strategy-to-clear-the-hiv-reservoir
#19
Edurne Garcia-Vidal, Marc Castellví, Maria Pujantell, Roger Badia, Antoni Jou, Lucia Gomez, Teresa Puig, Bonaventura Clotet, Ester Ballana, Eva Riveira-Muñoz, José A Esté
The persistence of HIV despite suppressive antiretroviral therapy is a major roadblock to HIV eradication. Current strategies focused on inducing the expression of latent HIV fail to clear the persistent reservoir, prompting the development of new approaches for killing HIV+ cells. Recently, acitretin has been proposed as a pharmacological innate cellular-defense network enhancer that led to virus reactivation and preferential death of infected cells. We have evaluated the capacity of acitretin to reactivate and/or facilitate immune-mediated clearance of HIV+ cells...
September 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28864951/time-course-of-cellular-hiv-dna-and-low-level-hiv-viremia-in-hiv-hcv%C3%A2-co-infected-patients-whose-hcv-infection-had-been-successfully-treated-with-directly-acting-antivirals
#20
Saverio G Parisi, Samantha Andreis, Monica Basso, Silvia Cavinato, Renzo Scaggiante, Marzia Franzetti, Massimo Andreoni, Giorgio Palù, Anna Maria Cattelan
This longitudinal study described cellular HIV-DNA changes and their correlation with HIV low-level plasma viremia (LLV) in HIV-HCV co-infected patients on successful antiretroviral and anti-HCV therapy by treatment with direct-acting antivirals (DAA). Thirty-nine patients were examined prior to the start of DAA (T0), after week 12 (T1) and 24 weeks (T2) of anti-HCV therapy. Cellular PBMC HIV-DNA was analysed as an absolute value and as the percentage of increase or decrease from T0 to T2. Patients were classified as having undetectable plasma HIV viraemia (UV) or LLV in the year before the start of anti-HCV treatment and within the T0-T2 study period...
September 1, 2017: Medical Microbiology and Immunology
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