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HIV reservoir

Zhujun Ao, Rong Zhu, Xiaoli Tan, Lisa Liu, Liyu Chen, Shuiping Liu, XiaoJian Yao
BACKGROUND: HIV-1 latency is a major obstacle for HIV-1 eradication. Extensive efforts are being directed toward the reactivation of latent HIV reservoirs with the aim of eliminating latently infected cells via the host immune system and/or virus-mediated cell lysis. RESULTS: We screened over 1,500 small molecules and kinase inhibitors and found that a small molecule, PKC412 (midostaurin, a broad-spectrum kinase inhibitor), can stimulate viral transcription and expression from the HIV-1 latently infected ACH2 cell line and primary resting CD4+ T cells...
October 21, 2016: Virology Journal
Julie Yamaguchi, Catherine A Brennan, Elodie Alessandri, Jean-Christophe Plantier, Gavin Cloherty, Michael G Berg
HIV-2 exhibits a natural history of infection distinct from HIV-1. Primarily found in West Africa and in only 10-20% of HIV infections in this region, patients with HIV-2 typically exhibit a slower progression to AIDS, lower viral loads, and decreased rates of transmission. Here we used next-generation sequencing (NGS) to determine the sequence and phylogenetic classification of 9 HIV-2 genomes. We identified a patient with a series of mutations in an invariant cytotoxic lymphocyte (CTL)-restricted gag epitope required for retroviral structure and replication, and implicated in long-term non-progression to AIDS...
October 19, 2016: AIDS Research and Human Retroviruses
Constanza Morén, Ingrid González-Casacuberta, Carmen Álvarez-Fernández, Maria Bañó, Marc Catalán-Garcia, Mariona Guitart-Mampel, Diana Luz Juárez-Flores, Ester Tobías, José Milisenda, Francesc Cardellach, Josep Maria Gatell, Sonsoles Sánchez-Palomino, Glòria Garrabou
To characterize mitochondrial/apoptotic parameters in chronically human immunodeficiency virus (HIV-1)-infected promonocytic and lymphoid cells which could be further used as therapeutic targets to test pro-mitochondrial or anti-apoptotic strategies as in vitro cell platforms to deal with HIV-infection. Mitochondrial/apoptotic parameters of U1 promonocytic and ACH2 lymphoid cell lines were compared to those of their uninfected U937 and CEM counterparts. Mitochondrial DNA (mtDNA) was quantified by rt-PCR while mitochondrial complex IV (CIV) function was measured by spectrophotometry...
October 18, 2016: Journal of Cellular and Molecular Medicine
Héloïse M Delagrèverie, Constance Delaugerre, Sharon R Lewin, Steven G Deeks, Jonathan Z Li
In chronic human immunodeficiency virus (HIV)-1 infection, long-lived latently infected cells are the major barrier to virus eradication and functional cure. Several therapeutic strategies to perturb, eliminate, and/or control this reservoir are now being pursued in the clinic. These strategies include latency reversal agents (LRAs) designed to reactivate HIV-1 ribonucleic acid transcription and virus production and a variety of immune-modifying drugs designed to reverse latency, block homeostatic proliferation, and replenish the viral reservoir, eliminate virus-producing cells, and/or control HIV replication after cessation of antiretroviral therapy...
October 2016: Open Forum Infectious Diseases
Sara Gianella, Jeff Taylor, Timothy R Brown, Andy Kaytes, Cristian L Achim, David J Moore, Susan J Little, Ron J Ellis, Davey M Smith
Despite extensive investigations, we still do not fully understand the dynamics of the total body HIV reservoir and how sub-reservoirs in various compartments relate to one another. Studies using macaque models are enlightening but eradication strategies will still need to be tested in humans. To take the next steps in understanding and eradicating HIV reservoirs throughout the body, we propose to develop a "peri-mortem translational research model" of HIV-infected individuals (called 'The Last Gift'), which is similar to existing models in cancer research...
October 14, 2016: AIDS
Gilles Darcis, Sophie Bouchat, Anna Kula, Benoit Van Driessche, Nadège Delacourt, Caroline Vanhulle, Véronique Avettand-Fenoel, Stéphane De Wit, Olivier Rohr, Christine Rouzioux, Carine Van Lint
OBJECTIVE: HIV-1 reservoirs are the major hurdle to virus clearance in cART-treated patients. An approach to eradicating HIV-1 involves reversing latency in cART-treated patients in order to make latent cells visible to the host immune system. Stimulation of patient cell cultures with LRAs ex vivo results in heterogeneous responses among HIV-infected patients. Determinants of this heterogeneity are unknown and consequently, important to determine. DESIGN AND METHODS: Here, we grouped and retrospectively analyzed the data from our two recent HIV-1 reactivation studies to investigate the role of the HIV-1 reservoir size in the reactivation capacity by LRAs in ex vivo cultures of CD8-depleted PBMCs isolated from 54 cART-treated patients and of resting CD4 T cells isolated from 30 cART-treated patients...
October 14, 2016: AIDS
Merlin L Robb, Jintanat Ananworanich
PURPOSE OF REVIEW: Understanding the characteristics of transmission during acute HIV infection (AHI) may inform targets for vaccine-induced immune interdiction. Individuals treated in AHI with a small HIV reservoir size may be ideal candidates for therapeutic HIV vaccines aiming for HIV remission (i.e. viremic control after treatment interruption). RECENT FINDINGS: The AHI period is brief and peak viremia predicts a viral set point that occurs 4-5 weeks following infection...
September 29, 2016: Current Opinion in HIV and AIDS
Céline Marban, Faezeh Forouzanfar, Amina Ait-Ammar, Faiza Fahmi, Hala El Mekdad, Fadoua Daouad, Olivier Rohr, Christian Schwartz
One of the top research priorities of the international AIDS society by the action "Towards an HIV Cure" is the purge or the decrease of the pool of all latently infected cells. This strategy is based on reactivation of latently reservoirs (the shock) followed by an intensifying combination antiretroviral therapy (cART) to kill them (the kill). The central nervous system (CNS) has potential latently infected cells, i.e., perivascular macrophages, microglial cells, and astrocytes that will need to be eliminated...
2016: Frontiers in Immunology
Xia Wang, Sanyi Tang, Xinyu Song, Libin Rong
HIV can infect cells via virus-to-cell infection or cell-to-cell viral transmission. These two infection modes may occur in a synergistic way and facilitate viral spread within an infected individual. In this paper, we developed an HIV latent infection model including both modes of transmission and time delays between viral entry and integration or viral production. We analysed the model by defining the basic reproductive number, showing the existence, positivity and boundedness of the solution, and proving the local and global stability of the infection-free and infected steady states...
October 12, 2016: Journal of Biological Dynamics
Valentin Le Douce, Faezeh Forouzanfar, Sebastian Eilebrecht, Benoit Van Driessche, Amina Ait-Ammar, Roxane Verdikt, Yoshihito Kurashige, Céline Marban, Virginie Gautier, Ermanno Candolfi, Arndt G Benecke, Carine Van Lint, Olivier Rohr, Christian Schwartz
Among many cellular transcriptional regulators, Bcl11b/CTIP2 and HGMA1 have been described to control the establishment and the persistence of HIV-1 latency in microglial cells, the main viral reservoir in the brain. In this present work, we identify and characterize a transcription factor i.e. HIC1, which physically interacts with both Bcl11b/CTIP2 and HMGA1 to co-regulate specific subsets of cellular genes and the viral HIV-1 gene. Our results suggest that HIC1 represses Tat dependent HIV-1 transcription...
October 11, 2016: Scientific Reports
Rahul Sampath, Nathan W Cummins, Andrew D Badley
HIV cure is now the focus of intense research after Timothy Ray Brown (the Berlin patient) set the precedent of being the first and only person cured. A major barrier to achieving this goal on a meaningful scale is an elimination of the latent reservoir, which is thought to comprise CD4-positive cells that harbor integrated, replication-competent HIV provirus. These cells do not express viral proteins, are indistinguishable from uninfected CD4 cells, and are thought to be responsible for HIV viral rebound-that occurs within weeks of combination anti retroviral therapy (cART) interruption...
2016: Journal of Cell Death
Guan-Han Li, Lisa Henderson, Avindra Nath
If we have any hope of achieving a cure for HIV infection, close attention to the cell types capable of getting infected with HIV is necessary. Of these cell types, astrocytes are the most ideal cell type for the formation of such a reservoir. These are long-lived cells with a very low turnover rate and are found in the brain and the gastrointestinal tract. Although astrocytes are evidently resistant to infection of cell-free HIV in vitro, these cells are efficiently infected via cell-to-cell contact by which immature HIV virions bud off lymphocytes and have ability directly bind to CXCR4 triggering the process of fusion in the absence of CD4...
October 6, 2016: Current HIV Research
Merlin L Robb, Jintanat Ananworanich
PURPOSE OF REVIEW: Understanding the characteristics of transmission during acute HIV infection (AHI) may inform targets for vaccine-induced immune interdiction. Individuals treated in AHI with a small HIV reservoir size may be ideal candidates for therapeutic HIV vaccines aiming for HIV remission (i.e. viremic control after treatment interruption). RECENT FINDINGS: The AHI period is brief and peak viremia predicts a viral set point that occurs 4-5 weeks following infection...
November 2016: Current Opinion in HIV and AIDS
K F Gurski, K A Hoffman
In 1992, Watts and May introduced a simple dynamical systems model of the spread of HIV based on disease transmission per partnership including the length of partnership duration. This model allowed for the treatment of concurrent partnerships, although it was hampered by the assumption of an important latent phase which generated a non-autonomous system. Subsequent models including concurrency have been based on networks, Monte Carlo, and stochastic simulations which lose a qualitative understanding of the effects of concurrency...
October 3, 2016: Mathematical Biosciences
Zora Melkova, Prakash Shankaran, Michaela Madlenakova, Josef Bodor
HIV-1 infection cannot be cured as it persists in latently infected cells that are targeted neither by the immune system nor by available therapeutic approaches. Consequently, a lifelong therapy suppressing only the actively replicating virus is necessary. The latent reservoir has been defined and characterized in various experimental models and in human patients, allowing research and development of approaches targeting individual steps critical for HIV-1 latency establishment, maintenance, and reactivation...
October 5, 2016: Folia Microbiologica
Xian Li, Hanxian Zeng, Pengfei Wang, Lu Lin, Lin Liu, Panpan Lu, Huanzhang Zhu
BACKGROUND: Current antiretroviral treatment (ART) cannot cure HIV-1 infection due to the presence of latent viral reservoirs. The "shock and kill" strategy is a promising approach to eliminate the viral reservoir. However, there are various limits existing in current latency-reversing agents, searching for new activators are urgently needed. OBJECTIVE: The present study aimed at investigating the ability of hymecromone and scoparone for activating HIV-1 from latent reservoirs...
October 3, 2016: Current HIV Research
Gabrielle Lê-Bury, Chantal Deschamps, Audrey Dumas, Florence Niedergang
Macrophages are phagocytic cells that play a major role at the crossroads between innate and specific immunity. They can be infected by the human immunodeficiency virus (HIV)-1 and because of their resistance to its cytopathic effects they can be considered to be persistent viral reservoirs. In addition, HIV-infected macrophages exhibit defective functions that contribute to the development of opportunistic diseases. The exact mechanism by which HIV-1 impairs the phagocytic response of macrophages was unknown...
2016: Journal of Visualized Experiments: JoVE
Sook-Kyung Lee, Shuntai Zhou, Pedro L Baldoni, Ean Spielvogel, Nancie M Archin, Michael G Hudgens, David M Margolis, Ronald Swanstrom
BACKGROUND: In this study, we measured the latent HIV-1 reservoir harboring replication-competent HIV-1 in resting CD4+ T cells in participants on highly active antiretroviral therapy (HAART), quantitating the frequency of latent infection through the use of a Primer ID-based Ultra Deep Sequencing Assay (UDSA), in comparison to the readout of the quantitative viral outgrowth assay (QVOA). METHODS: Viral RNA derived from culture wells of QVOA that scored as HIV-1 p24 capsid (CA) antigen-positive were tagged with a specific barcode during cDNA synthesis, and the sequences within the V1-V3 region of the HIV-1 env gene were analyzed for diversity using the Primer ID-based paired-end MiSeq platform...
September 27, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Hoyong Lim, Kyung-Chang Kim, Junseock Son, Younghyun Shin, Cheol-Hee Yoon, Chun Kang, Byeong-Sun Choi
HIV-1 reservoirs remain a major barrier to HIV-1 eradication. Although combination antiretroviral therapy (cART) can successfully reduce viral replication, it cannot reactivate HIV-1 provirus in this reservoir. Therefore, HIV-1 provirus reactivation strategies by cell activation or epigenetic modification are proposed for the eradication of HIV-1 reservoirs. Although treatment with the protein kinase A (PKA) activator cyclic AMP (cAMP) or epigenetic modifying agents such as histone deacetylase inhibitors (HDACi) alone can induce HIV-1 reactivation in latently infected cells, the synergism of these agents has not been fully evaluated...
September 24, 2016: Virus Research
P Gale
The host reservoir of Zaire ebolavirus (EBOV) remains elusive. One suggestion is that EBOV emerges in mammals when the precursor virus jumps from mayflies (or other riverine insects) to insectivorous bats. However, this does not fit with the current view that filoviruses cannot infect arthropods. Here, it is first argued that the evidence that arthropods are refractory is not definitive. Second, it is proposed that a combination of filovirus filament length and the high temperature (~42°C) experienced by an insect virus ingested by a flying bat, together with the large number of insects eaten by bats (e...
September 26, 2016: Transboundary and Emerging Diseases
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