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https://www.readbyqxmd.com/read/28630490/pyroptosis-superinfection-and-the-maintenance-of-the-latent-reservoir-in-hiv-1-infection
#1
Dominik Wodarz, David N Levy
A long-lived reservoir of latently infected T cells prevents antiretroviral therapy from eliminating HIV-1 infection. Furthering our understanding of the dynamics of latency generation and maintenance is therefore vital to improve treatment outcome. Using mathematical models and experiments, we suggest that the death of latently infected cells brought about by pyroptosis, or to a lesser extent by superinfection, might be key mechanisms to account for the size and composition of the latent reservoir. Pyroptosis is a form of cell death that occurs in a resting (and thus latently infected) T cell when a productively infected cell attempts cell-to-cell transmission of virus...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28628632/increasing-procaspase-8-expression-using-repurposed-drugs-to-induce-hiv-infected-cell-death-in-ex-vivo-patient-cells
#2
Rahul Sampath, Nathan W Cummins, Sekar Natesampillai, Gary D Bren, Thomas D Chung, Jason Baker, Keith Henry, Amélie Pagliuzza, Andrew D Badley
HIV persists because a reservoir of latently infected CD4 T cells do not express viral proteins and are indistinguishable from uninfected cells. One approach to HIV cure suggests that reactivating HIV will activate cytotoxic pathways; yet when tested in vivo, reactivating cells do not die sufficiently to reduce cell-associated HIV DNA levels. We recently showed that following reactivation from latency, HIV infected cells generate the HIV specific cytotoxic protein Casp8p41 which is produced by HIV protease cleaving procaspase 8...
2017: PloS One
https://www.readbyqxmd.com/read/28628041/hiv-persistence-clonal-expansion-of-cells-in-the-latent-reservoir
#3
Kyungyoon J Kwon, Robert F Siliciano
While antiretroviral therapy (ART) can reduce HIV-1 to undetectable levels, the virus generally reappears if treatment is stopped. Resurgence of the virus is due to the reactivation of T cells harboring latent integrated provirus, and recent studies indicate that proliferation of these latently infected cells helps maintain the HIV-1 reservoir. In this issue of the JCI, Lee et al. evaluated CD4+ T cell subsets to determine whether certain populations are more likely to harbor full-length, replication-competent provirus...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28625133/recent-advances-in-targeting-the-hiv-1-tat-tar-complex
#4
Fardokht A Abulwerdi, Stuart F J Le Grice
Following seminal discoveries by Rosen and co-workers in 1985, the HIV-1 TAR has emerged as one of the most extensively studied regulatory elements of the HIV-1 genome. Located adjacent to the long terminal repeat promoter, this cis-acting motif, in conjunction with the viral Tat protein, plays a critical role in viral genomic RNA synthesis via modification of the transcription complex. As such, the Tat/TAR axis has been the subject of intense efforts aimed at developing therapeutic interventions, directed against both the protein and nucleic acid components...
June 15, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28605173/barriers-to-hiv-remission-research-in-low-and-middle-income-countries
#5
REVIEW
Theresa Rossouw, Joseph D Tucker, Gert U van Zyl, Kenly Sikwesi, Catherine Godfrey
INTRODUCTION: HIV eradication and remission research has largely taken place in high-income countries. In low- and middle-income countries (LMIC), there may be factors that have a substantial impact on the size of the latent HIV reservoir and the immunological response to infection. If a curative strategy is to be available to all HIV-infected individuals, these factors must be understood. METHODS: We use a scoping review to examine the literature on biological factors that may have an impact on HIV persistence in LMIC...
June 5, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28603436/reduced-adherence-to-antiretroviral-therapy-is-associated-with-residual-low-level-viremia
#6
Franco Maggiolo, Elisa Di Filippo, Laura Comi, Annapaola Callegaro, Giorgio L Colombo, Sergio Di Matteo, Daniela Valsecchi, Marco Rizzi
The source and significance of residual low-level viremia (LLV) during combinational antiretroviral therapy (cART) remain a matter of controversy. It is unclear whether residual viremia depends on ongoing release of HIV from the latent reservoir or if viral replication contributes to LLV. We examined the relationship between adherence and LLV. Adherence was estimated by pharmacy refill and dichotomized as ≥95% or <95%. Plasma HIV-RNA was determined, with an ultrasensitive test having a limit of detection of 3 copies/mL at least 2 times over the follow-up period...
2017: Pragmatic and Observational Research
https://www.readbyqxmd.com/read/28590334/a-decade-of-learning-about-the-hiv-reservoir-new-insights-into-latent-infection
#7
Kristin N Harper
No abstract text is available yet for this article.
June 5, 2017: AIDS
https://www.readbyqxmd.com/read/28579286/hiv-aids-infection-the-beginning-of-the-end-for-today-s-greatest-pandemic
#8
F Gutiérrez
Recently, there have been significant advances in the fight against human immunodeficiency virus, which have increased the hopes of definitively halting its dissemination and of starting the decline of the epidemic it has caused. Transmission of the infection was drastically reduced when infected patients were given antiretroviral treatments, which boosted the diffusion of treatments to middle- and low-income countries. Global therapy coverage has doubled in recent years; meanwhile the incidence of new infections has decreased...
June 1, 2017: Revista Clínica Española
https://www.readbyqxmd.com/read/28553933/novel-assay-reveals-a-large-inducible-replication-competent-hiv-1-reservoir-in-resting-cd4-t-cells
#9
Anwesha Sanyal, Robbie B Mailliard, Charles R Rinaldo, Deena Ratner, Ming Ding, Yue Chen, Jennifer M Zerbato, Nicholas S Giacobbi, Narasimhan J Venkatachari, Bruce K Patterson, Amanda Chargin, Nicolas Sluis-Cremer, Phalguni Gupta
Although antiretroviral therapy can suppress HIV-1 infection to undetectable levels of plasma viremia, integrated latent HIV-1 genomes that encode replication-competent virus persist in resting CD4(+) T cells. This latent HIV-1 reservoir represents a major barrier to a cure. Currently, there are substantial efforts to identify therapeutic approaches that will eliminate or reduce the size of this latent HIV-1 reservoir. In this regard, a sensitive assay that can accurately and rapidly quantify inducible, replication-competent latent HIV-1 from resting CD4(+) T cells is essential for HIV-1 eradication studies...
May 29, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28539614/the-ccr5-antagonist-maraviroc-reverses-hiv-1-latency-in-vitro-alone-or-in-combination-with-the-pkc-agonist-bryostatin-1
#10
María Rosa López-Huertas, Laura Jiménez-Tormo, Nadia Madrid-Elena, Carolina Gutiérrez, Sara Rodríguez-Mora, Mayte Coiras, José Alcamí, Santiago Moreno
A potential strategy to cure HIV-1 infection is to use latency reversing agents (LRAs) to eliminate latent reservoirs established in resting CD4+ T (rCD4+) cells. As no drug has been shown to be completely effective, finding new drugs and combinations are of increasing importance. We studied the effect of Maraviroc (MVC), a CCR5 antagonist that activates NF-κB, on HIV-1 replication from latency. HIV-1-latency models based on CCL19 or IL7 treatment, before HIV-1 infection were used. Latently infected primary rCD4+ or central memory T cells were stimulated with MVC alone or in combination with Bryostatin-1, a PKC agonist known to reverse HIV-1 latency...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539449/anti-hiv-1-adcc-antibodies-following-latency-reversal-and-treatment-interruption
#11
Wen Shi Lee, Anne B Kristensen, Thomas A Rasmussen, Martin Tolstrup, Lars Østergaard, Ole S Søgaard, Bruce D Wines, P Mark Hogarth, Arnold Reynaldi, Miles P Davenport, Sean Emery, Janaki Amin, David A Cooper, Virginia L Kan, Julie Fox, Henning Gruell, Matthew S Parsons, Stephen J Kent
There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRA) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28537062/evaluation-of-the-immunogenicity-and-impact-on-the-latent-hiv-1-reservoir-of-a-conserved-region-vaccine-mva-hivconsv-in-antiretroviral-therapy-treated-subjects
#12
Gemma Hancock, Sara Morón-López, Jakub Kopycinski, Maria C Puertas, Eleni Giannoulatou, Annie Rose, Maria Salgado, Emma-Jo Hayton, Alison Crook, Catharine Morgan, Brian Angus, Fabian Chen, Hongbing Yang, Javier Martinez-Picado, Tomas Hanke, Lucy Dorrell
INTRODUCTION: Vaccines may be key components of a curative strategy for HIV-1. We investigated whether a novel immunogen, HIVconsv, designed to re-direct T cell responses to conserved viral epitopes, could impact the HIV-1 reservoir in chronic antiretroviral therapy (ART)-treated subjects when delivered by modified vaccinia virus Ankara (MVA). METHODS: Nineteen virologically suppressed individuals were randomized to receive vaccinations with MVA.HIVconsv (5.5 × 10(7) plaque-forming units, pfu, n = 8; 2...
May 19, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28535179/reduced-frequency-of-cells-latently-infected-with-replication-competent-hiv-1-in-virally-suppressed-individuals-living-in-rakai-uganda
#13
Jessica L Prodger, Jun Lai, Steven J Reynolds, Jeanne C Keruly, Richard D Moore, Jingo Kasule, Taddeo Kityamuweesi, Paul Buule, David Serwadda, Martha Nason, Adam A Capoferri, Stephen F Porcella, Robert F Siliciano, Andrew D Redd, Janet D Siliciano, Thomas C Quinn
Background: HIV-1 persists in latently infected resting CD4+ T cells (rCD4), posing a major barrier to curing HIV-1 infection. Previous studies have quantified this pool of latently infected cells in Americans; however, no study has quantified this reservoir in sub-Saharan Africans, who make up the largest population of HIV-1-infected individuals globally. Methods: Peripheral blood was collected from 70 virally suppressed HIV-1-infected individuals from Rakai District, Uganda, who had initiated antiretroviral therapy (ART) during chronic infection...
May 23, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28534887/when-is-early-antiretroviral-therapy-early-enough-for-hiv-remission
#14
Eva Poveda, Manuelo Cresp
Several strategies to reduce and control the HIV reservoir are being evaluating to achieve the great challenge of HIV remission or functional cure. Some of these are based on immune and gene therapy, or in the use of agents with latency reversing properties. Moreover, acute HIV infection and the impact of early antiretroviral treatment (ART) initiation is another key issue of current research. It has been demonstrated that ART initiation during acute HIV infection minimizes the establishment of the latent HIV reservoir...
May 23, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28529952/advancements-in-developing-strategies-for-sterilizing-and-functional-hiv-cures
#15
REVIEW
Wei Xu, Haoyang Li, Qian Wang, Chen Hua, Hanzhen Zhang, Weihua Li, Shibo Jiang, Lu Lu
Combined antiretroviral therapy (cART) has been successful in prolonging lifespan and reducing mortality of patients infected with human immunodeficiency virus (HIV). However, the eradication of latent HIV reservoirs remains a challenge for curing HIV infection (HIV cure) because of HIV latency in primary memory CD4(+) T cells. Currently, two types of HIV cures are in development: a "sterilizing cure" and a "functional cure." A sterilizing cure refers to the complete elimination of replication-competent proviruses in the body, while a functional cure refers to the long-term control of HIV replication without treatment...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28529033/high-throughput-characterization-of-hiv-1-reservoir-reactivation-using-a-single-cell-in-droplet-pcr-assay
#16
Robert W Yucha, Kristen S Hobbs, Emily Hanhauser, Louise E Hogan, Wildaliz Nieves, Mehmet O Ozen, Fatih Inci, Vanessa York, Erica A Gibson, Cassandra Thanh, Hadi Shafiee, Rami El Assal, Maja Kiselinova, Yvonne P Robles, Helen Bae, Kaitlyn S Leadabrand, ShuQi Wang, Steven G Deeks, Daniel R Kuritzkes, Utkan Demirci, Timothy J Henrich
Reactivation of latent viral reservoirs is on the forefront of HIV-1 eradication research. However, it is unknown if latency reversing agents (LRAs) increase the level of viral transcription from cells producing HIV RNA or harboring transcriptionally-inactive (latent) infection. We therefore developed a microfluidic single-cell-in-droplet (scd)PCR assay to directly measure the number of CD4(+) T cells that produce unspliced (us)RNA and multiply spliced (ms)RNA following ex vivo latency reversal with either an histone deacetylase inhibitor (romidepsin) or T cell receptor (TCR) stimulation...
May 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28520968/measuring-the-size-of-the-latent-human-immunodeficiency-virus-reservoir-the-present-and-future-of-evaluating-eradication-strategies
#17
Timothy J Henrich, Steven G Deeks, Satish K Pillai
One of the major barriers to the successful design and implementation of human immunodeficiency virus (HIV) curative strategies is the limited ability to sensitively, specifically, and precisely quantify and characterize the whole-body burden of replication-competent HIV in individuals on effective antiretroviral therapy. Here, we review the development and validation of assays that directly and indirectly measure the size and distribution of the reservoir in blood and tissues. We also discuss the role that treatment interruptions will have in validating these assays and ultimately as a "proof of cure...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520966/clonal-expansion-of-human-immunodeficiency-virus-infected-cells-and-human-immunodeficiency-virus-persistence-during-antiretroviral-therapy
#18
James I Mullins, Lisa M Frenkel
The latent HIV-1 reservoir in blood decays very slowly, even during prolonged suppression of viral replication by antiretroviral therapy (ART). Mechanisms for reservoir persistence include replenishment through low-level viral replication, longevity and homeostatic proliferation of memory T cells, and most recently appreciated, clonal expansion of HIV-infected cells. Clonally expanded cells make up a large and increasing fraction of the residual infected cell population on ART, and insertion of HIV proviruses into certain host cellular genes has been associated with this proliferation...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520963/humoral-and-innate-antiviral-immunity-as-tools-to-clear-persistent-hiv-infection
#19
Guido Ferrari, Justin Pollara, Georgia D Tomaras, Barton F Haynes
Human immunodeficiency virus (HIV) type 1 uses the CD4 molecule as its principal receptor to infect T cells. HIV-1 integrates its viral genome into the host cell, leading to persistent infection wherein HIV-1 can remain transcriptionally silent in latently infected CD4+ T cells. On reactivation of replication-competent provirus, HIV-1 envelope glycoproteins (Env) are expressed and accumulate on the cell surface, allowing infected cells to be detected and targeted by endogenous immune responses or immune interventions...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28518089/laparoscopic-technique-for-serial-collection-of-liver-and-mesenteric-lymph-nodes-in-macaques
#20
Alexander S Zevin, Cassie Moats, Drew May, Solomon Wangari, Charlene Miller, Joel Ahrens, Naoto Iwayama, Megan Brown, Debbie Bratt, Nichole R Klatt, Jeremy Smedley
The mesenteric lymph nodes (MLN) and the liver are exposed to microbes and microbial products from the gastrointestinal (GI) tract, making them immunologically unique. The GI tract and associated MLN are sites of early viral replication in human immunodeficiency virus (HIV) infection and the MLN are likely important reservoir sites that harbor latently-infected cells even after prolonged antiretroviral therapy (ART). The liver has been shown to play a significant role in immune responses to lentiviruses and appears to play a significant role in clearance of virus from circulation...
May 2, 2017: Journal of Visualized Experiments: JoVE
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