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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
#1
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
#2
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
#3
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
#4
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/28520969/cell-mediated-immunity-to-target-the-persistent-human-immunodeficiency-virus-reservoir
#5
James L Riley, Luis J Montaner
Effective clearance of virally infected cells requires the sequential activity of innate and adaptive immunity effectors. In human immunodeficiency virus (HIV) infection, naturally induced cell-mediated immune responses rarely eradicate infection. However, optimized immune responses could potentially be leveraged in HIV cure efforts if epitope escape and lack of sustained effector memory responses were to be addressed. Here we review leading HIV cure strategies that harness cell-mediated control against HIV in stably suppressed antiretroviral-treated subjects...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520968/measuring-the-size-of-the-latent-human-immunodeficiency-virus-reservoir-the-present-and-future-of-evaluating-eradication-strategies
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28512685/modeling-brain-lentiviral-infections-during-antiretroviral-therapy-in-aids
#10
Weston C Roda, Michael Y Li, Michael S Akinwumi, Eugene L Asahchop, Benjamin B Gelman, Kenneth W Witwer, Christopher Power
Understanding HIV-1 replication and latency in different reservoirs is an ongoing challenge in the care of patients with HIV/AIDS. A mathematical model was created to describe and predict the viral dynamics of HIV-1 and SIV infection within the brain during effective combination antiretroviral therapy (cART). The mathematical model was formulated based on the biology of lentiviral infection of brain macrophages and used to describe the dynamics of transmission and progression of lentiviral infection in brain...
May 16, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28511815/signature-of-the-sleeper-cell-a-biomarker-of-hiv-latency-revealed
#11
Satish K Pillai, Steven G Deeks
HIV establishes a reservoir in latently infected T cells, and this reservoir has long hampered curative approaches. A recent study by Descours et al. identifies CD32a as a marker of latently infected T cells, potentially opening the way to the development of strategies that directly target this critical HIV reservoir.
May 13, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28511559/migrating-microbes-what-pathogens-can-tell-us-about-population-movements-and-human-evolution
#12
Charlotte J Houldcroft, Jean-Baptiste Ramond, Riaan F Rifkin, Simon J Underdown
BACKGROUND: The biology of human migration can be observed from the co-evolutionary relationship with infectious diseases. While many pathogens are brief, unpleasant visitors to human bodies, others have the ability to become life-long human passengers. The story of a pathogen's genetic code may, therefore, provide insight into the history of its human host. The evolution and distribution of disease in Africa is of particular interest, because of the deep history of human evolution in Africa, the presence of a variety of non-human primates, and tropical reservoirs of emerging infectious diseases...
May 16, 2017: Annals of Human Biology
https://www.readbyqxmd.com/read/28503303/a-study-on-hiv-syphilis-and-hepatitis-b-and-c-virus-infections-among-female-sex-workers-in-the-republic-of-congo
#13
Fabien Roch Niama, Nadia Claricelle Loukabou Bongolo, Pembe Issamou Mayengue, Franck Fortuné Mboussou, Edith Sophie Kombo Bayonne, Florian Michael Kouckodila Nzingoula, Louis Regis Dossou-Yovo, Igor Louzolo, Mandingha Kosso Etoka-Beka, Achile Lanzy, Irène Yameogo, Davy Louvouezo, Simon Charles Kobawila, Marie-Francke Puruhence, Henri Joseph Parra
BACKGROUND: Female Sex Workers (FSWs) are considered to be at high risk for transmission of Sexually Transmitted Infections (STIs) and are defined as a priority of the national HIV/AIDS response in the Republic of Congo (RoC). However, no data are available regarding STIs in this group. This study aimed to determine the prevalences of HIV, syphilis and hepatitis B and C among FSWs in five cities in the country. METHODS: A cross-sectional study was conducted from November 2(nd) 2011 to May 15(th) 2012...
2017: Archives of Public Health, Archives Belges de Santé Publique
https://www.readbyqxmd.com/read/28500326/intranasal-drug-delivery-of-small-interfering-rna-targeting-beclin1-encapsulated-with-polyethylenimine-pei-in-mouse-brain-to-achieve-hiv-attenuation
#14
Myosotys Rodriguez, Jessica Lapierre, Chet Raj Ojha, Ajeet Kaushik, Elena Batrakova, Fatah Kashanchi, Seth M Dever, Madhavan Nair, Nazira El-Hage
We previously reported that activation of the host autophagic protein, Beclin1, by HIV-1 infection represents an essential mechanism in controlling HIV replication and viral-induced inflammatory responses in microglial cells. Existing antiretroviral therapeutic approaches have been limited in their ability to cross the blood-brain barrier effectively and recognize and selectively eliminate persistent HIV-infected brain reservoirs. In the present study and for the first time, the bio-distribution and efficacy of noninvasive intranasal delivery of small interfering RNA (siRNA) against the Beclin1 gene using the cationic linear polyethylenimines (PEI) as a gene carrier was investigated in adult mouse brain...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28498985/hiv-antibodies-detect-hiv-persistence-and-low-level-viral-replication
#15
Sheila M Keating, Christopher D Pilcher, Vivek Jain, Mila Lebedeva, Dylan Hampton, Mohamed Abdel-Mohsen, Xutao Deng, Gary Murphy, Alex Welte, Shelley N Facente, Frederick Hecht, Steven G Deeks, Satish K Pillai, Michael P Busch
BACKGROUND: HIV antibodies are generated and maintained by ongoing systemic expression of HIV antigen. We investigated whether HIV antibody responses as measured by high-throughput quantitative and qualitative assays could be used to indirectly measure persistent HIV replication in individuals on antiretroviral therapy (ART). METHODS: HIV antibody measurements were made over time on and off suppressive ART and were compared to measures of HIV reservoir size and expression of anti-viral restriction factors...
May 11, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28490595/sensing-of-hiv-1-entry-triggers-a-type-i-interferon-response-in-human-primary-macrophages
#16
Jérémie Decalf, Marion Desdouits, Vasco Rodrigues, François-Xavier Gobert, Matteo Gentili, Santy Marques-Ladeira, Célia Chamontin, Marylène Mougel, Bruna Cunha de Alencar, Philippe Benaroch
Along with CD4+ T lymphocytes, macrophages are a major cellular source of HIV-1 replication, and a potential viral reservoir. Following entry and reverse transcription in macrophages, cloaking of the viral cDNA by the HIV-1 capsid limits its cytosolic detection, enabling efficient replication. However, whether incoming HIV-1 particles are sensed by macrophages prior to reverse-transcription, remains unclear. Here, we show that HIV-1 triggers a broad expression of interferon-stimulated genes (ISG) in monocyte-derived macrophages within a few hours after infection...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28486838/brain-microglial-cells-are-highly-susceptible-to-hiv-1-infection-and-spread
#17
Jennifer J Cenker, Ryan D Stultz, David McDonald
Macrophages are a target of HIV-1 infection and may serve as an important reservoir of the virus in the body, particularly after depletion of CD4+ T cells in HIV/AIDS. Recently, sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1) was identified as the major restriction factor of HIV-1 infection in myeloid cells. SAMHD1 is targeted for proteolytic degradation by Vpx, a viral protein encoded by HIV-2 and many SIVs but not HIV-1. In this study, we assessed SAMHD1 restriction in in vitro differentiated macrophages and in freshly isolated macrophages from the lungs, abdomen, and brain...
May 9, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28484447/hiv-1-and-siv-predominantly-use-ccr5-expressed-on-a-precursor-population-to-establish-infection-in-t-follicular-helper-cells
#18
Yin Xu, Chansavath Phetsouphanh, Kazuo Suzuki, Anu Aggrawal, Stephanie Graff-Dubois, Michael Roche, Michelle Bailey, Sheilajen Alcantara, Kieran Cashin, Rahuram Sivasubramaniam, Kersten K Koelsch, Brigitte Autran, Richard Harvey, Paul R Gorry, Arnaud Moris, David A Cooper, Stuart Turville, Stephen J Kent, Anthony D Kelleher, John Zaunders
BACKGROUND: T follicular helper (Tfh) cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4(+) T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28480237/gag-specific-cd8-t-cell-proliferation-is-associated-with-higher-peripheral-blood-levels-of-transforming-growth-factor-%C3%AE-and-gut-homing-t-cells-in-youths-perinatally-infected-with-human-immunodeficiency-virus-1-the-anrs-ep38-immip-study
#19
Josiane Warszawski, Véronique Avettand-Fenoel, Christine Rouzioux, Daniel Scott-Algara, Thomas Montange, Céline Didier, Jérôme Le Chenadec, Jean-Paul Viard, Catherine Dollfus, Stéphane Blanche, Florence Buseyne
BACKGROUND: Gag-specific T lymphocytes play a key role in the control of human immunodeficiency virus (HIV) replication. Their restoration will be important for future reservoir targeting strategies. In this study, we aimed to identify immune correlates of Gag-specific CD8 T-cell proliferation in youths with perinatally acquired HIV-1 infection. METHODS: The ANRS-EP38-IMMIP study included youths of 15 to 24 years of age. Fifty-three were taking combination anti-retroviral therapy and aviremic at the time of the study and had undergone valid 5-6-carboxyfluorescein diacetate succimidyl ester-based flow cytometry T-cell proliferation assays...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28474225/trans-dissemination-of-exosomes-from-hiv-1-infected-cells-fosters-both-hiv-1-trans-infection-in-resting-cd4-t-lymphocytes-and-reactivation-of-the-hiv-1-reservoir
#20
Chiara Chiozzini, Claudia Arenaccio, Eleonora Olivetta, Simona Anticoli, Francesco Manfredi, Flavia Ferrantelli, Gabriella d'Ettorre, Ivan Schietroma, Mauro Andreotti, Maurizio Federico
Intact HIV-1 and exosomes can be internalized by dendritic cells (DCs) through a common pathway leading to their transmission to CD4(+) T lymphocytes by means of mechanisms defined as trans-infection and trans-dissemination, respectively. We previously reported that exosomes from HIV-1-infected cells activate both uninfected quiescent CD4(+) T lymphocytes, which become permissive to HIV-1, and latently infected cells, with release of HIV-1 particles. However, nothing is known about the effects of trans-dissemination of exosomes produced by HIV-1-infected cells on uninfected or latently HIV-1-infected CD4(+) T lymphocytes...
May 4, 2017: Archives of Virology
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