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HIV reservoir

Kiran T Thakur, Alexandra Boubour, Deanna Saylor, Mitashee Das, David R Bearden, Gretchen L Birbeck
: Neurological conditions associated with HIV remain major contributors to morbidity and mortality and are increasingly recognized in the aging population on long-standing combination antiretroviral therapy (cART). Importantly, growing evidence shows that the CNS may serve as a reservoir for viral replication, which has major implications for HIV eradication strategies. Though there has been major progress in the last decade in our understanding of the pathogenesis, burden, and impact of neurological conditions associated with HIV infection, significant scientific gaps remain...
March 15, 2018: AIDS
Thomas Joshua Pasvol, Caroline Foster, Sarah Fidler
PURPOSE OF REVIEW: Successful roll-out of paediatric antiretroviral therapy (ART) has led to a significant increase in survival of adolescents and young people growing up with HIV. Those on suppressive ART since childhood represent a unique group particularly well positioned to interrupt ART and achieve post-treatment control (PTC), or HIV remission. This maybe a consequence of early and sustained treatment since infancy, the small size of the HIV reservoir, the presence of a functioning thymus and a more 'flexible' immune system better able to respond to novel immune therapeutic interventions when compared with adults who acquired HIV at a time of immunological maturity and thymic involution...
March 14, 2018: Current Opinion in HIV and AIDS
Li Huang, Wei-Hong Lai, Lei Zhu, Wei Li, Lei Wei, Kuo-Hsiung Lee, Lan Xie, Chin-Ho Chen
We have previously reported gnidimacrin (GM), a protein kinase C (PKC) agonist, significantly reduces the frequency of HIV-1 latently infected cells in peripheral blood mononuclear cells (PBMCs) from patients undergoing successful antiretroviral therapy at low picomolar concentrations ex vivo , which is distinct from other latency reversing agents. In this study, we demonstrate that strong viral reactivation by GM is a mechanism for elimination of latently infected cells, and a histone deacetylase inhibitor (HDACI), a thiophenyl benzamide (TPB), further potentiated the efficacy of GM against latent HIV-1...
March 8, 2018: ACS Medicinal Chemistry Letters
Monica Vaccari, Genoveffa Franchini
Germinal centers (GCs) are organized lymphoid tissue microstructures where B cells proliferate and differentiate into memory B cells and plasma cells. A few distinctive subsets of highly specialized T cells gain access to the GCs by expressing the B cell zone-homing C-X-C chemokine receptor type 5 (CXCR5) while losing the T cell zone-homing chemokine receptor CCR7. Help from T cells is critical to induce B cell proliferation and somatic hyper mutation and to limit GC reactions. CD4+ T follicular helper (TFH ) cells required for the formation of GCs and for the generation of long-lived, high-affinity B cells...
2018: Frontiers in Immunology
Victoria P Strouvelle, Dominique L Braun, Valentina Vongrad, Alexandra U Scherrer, Yik Lim Kok, Roger D Kouyos, Marcel Stöckle, Andri Rauch, Katharine Darling, Matthias Hoffmann, Karin J Metzner, Huldrych F Günthard
Pegylated interferon-alpha (pIFN-α) is suggested to lower HIV-1 DNA load in antiretroviral therapy (ART) treated patients. We studied the kinetics of total HIV-1 DNA levels in 40 HIV-1/hepatitis C (HCV) coinfected patients, treated with pIFN-α for HCV and categorized into three groups according to start of ART: Chronic HIV-1 infection (n=22), acute HIV-1 infection (n=8), no-ART (n=10). Total HIV-1 DNA levels were quantified in 247 PBMC samples and remained stable before, during, and after pIFN-α treatment in all three groups...
March 8, 2018: Journal of Infectious Diseases
Daniel Sauter, Frank Kirchhoff
HIV-1, the main causative agent of AIDS, and related primate lentiviruses show a striking ability to efficiently replicate throughout the lifetime of an infected host. In addition to their high variability, the acquisition of several accessory genes has enabled these viruses to efficiently evade or counteract seemingly strong antiviral immune responses. The respective viral proteins, i.e. Vif, Vpr, Vpu, Vpx and Nef, show a stunning functional diversity, acting by various mechanisms and targeting a large variety of cellular factors involved in innate and adaptive immunity...
February 23, 2018: Cytokine & Growth Factor Reviews
Saverio G Parisi, Samantha Andreis, Carlo Mengoli, Nicola Menegotto, Silvia Cavinato, Renzo Scaggiante, Massimo Andreoni, Giorgio Palù, Monica Basso, Anna Maria Cattelan
Soluble CD163, soluble CD14 and cellular HIV-1-DNA levels reflect two different aspects of HIV infection: immune activation and the reservoir of infected cells. The aim of this study was to describe their relationships in a cohort of HIV-HCV co-infected patients successfully treated for both HCV and HIV infections. Fifty-five patients were recruited and studied prior to the start of direct-acting antivirals (DAAs) (T0), at week 12 of DAA treatment (T1) and 24 weeks after T0 (T2). The subjects were classified as having undetectable plasma HIV viraemia (UV) or low-level viraemia (LLV) in the 18 months before T2...
March 9, 2018: Medical Microbiology and Immunology
Harshana S De Silva Feelixge, Daniel Stone, Pavitra Roychoudhury, Martine Aubert, Keith R Jerome
Chronic viral infections remain a major public health issue affecting millions of people worldwide. Highly active antiviral treatments have significantly improved prognosis and infection-related morbidity and mortality, but have failed to eliminate persistent viral forms. Therefore, new strategies to either eradicate or control these viral reservoirs are paramount to allow patients to stop antiretroviral therapy and realize a cure. Viral genome disruption based on gene editing by programmable endonucleases is one promising curative gene therapy approach...
March 9, 2018: ACS Infectious Diseases
Jeffy George, Joseph J Mattapallil
Human immunodeficiency virus (HIV) establishes life-long latency in infected individuals. Although highly active antiretroviral therapy (HAART) has had a significant impact on the course of HIV infection leading to a better long-term outcome, the pool of latent reservoir remains substantial even under HAART. Numerous approaches have been under development with the goal of eradicating the latent HIV reservoir though with limited success. Approaches that combine immune-mediated control of HIV to activate both the innate and the adaptive immune system under suppressive therapy along with "shock and kill" drugs may lead to a better control of the reactivated virus...
2018: Frontiers in Immunology
Lucie Bracq, Maorong Xie, Serge Benichou, Jérôme Bouchet
While HIV-1 infection of target cells with cell-free viral particles has been largely documented, intercellular transmission through direct cell-to-cell contact may be a predominant mode of propagation in host. To spread, HIV-1 infects cells of the immune system and takes advantage of their specific particularities and functions. Subversion of intercellular communication allows to improve HIV-1 replication through a multiplicity of intercellular structures and membrane protrusions, like tunneling nanotubes, filopodia, or lamellipodia-like structures involved in the formation of the virological synapse...
2018: Frontiers in Immunology
Jesús Rodríguez-Muñoz, Santiago Moreno
The disadvantages of the long-term administration of antiretroviral therapy as well as the huge number of affected persons have placed the cure of HIV as a primary goal of Public Health. HIV may persist in the organism by at least four mechanisms: a latently infected cellular reservoir, the persistent replication of HIV in spite of ART, anatomic sanctuaries, and the immune dysfunction. Several strategies directed against these mechanisms have been developed. With all this, a complete eradication of HIV has been achieved in a patient using the transplantation of haemopoietic stem cells that were resistant to HIV-infection, and there are examples of functional cure either spontaneously (elite controllers) or after antiretroviral therapy (post-treatment controllers)...
March 3, 2018: Enfermedades Infecciosas y Microbiología Clínica
Eileen P Scully
PURPOSE OF REVIEW: This review will outline the multilevel effects of biological sex on HIV acquisition, pathogenesis, treatment response, and prospects for cure. Potential mechanisms will be discussed along with future research directions. RECENT FINDINGS: HIV acquisition risk is modified by sex hormones and the vaginal microbiome, with the latter acting through both inflammation and local metabolism of pre-exposure prophylaxis drugs. Female sex associates with enhanced risk for non-AIDS morbidities including cardiovascular and cerebrovascular disease, suggesting different inflammatory profiles in men and women...
March 5, 2018: Current HIV/AIDS Reports
Helen R Fryer, Steven M Wolinsky, Angela R McLean
Although antiretroviral drug therapy suppresses human immunodeficiency virus-type 1 (HIV-1) to undetectable levels in the blood of treated individuals, reservoirs of replication competent HIV-1 endure. Upon cessation of antiretroviral therapy, the reservoir usually allows outgrowth of virus and approaches to targeting the reservoir have had limited success. Ongoing cycles of viral replication in regions with low drug penetration contribute to this persistence. Here, we use a mathematical model to illustrate a new approach to eliminating the part of the reservoir attributable to persistent replication in drug sanctuaries...
March 2, 2018: PLoS Computational Biology
Chen Huan, Zhaolong Li, Shanshan Ning, Hong Wang, Xiao-Fang Yu, Wenyan Zhang
The HIV-1 reservoir is a major obstacle to complete eradication of the virus. Although many proteins and RNAs have been characterized as regulators in HIV-1/AIDS pathogenesis and latency, only a few long non-coding RNAs (lncRNAs) have been shown to be closely associated with HIV-1 replication and latency. Here, we demonstrated that lncRNA uc002yug.2 plays a key role in HIV-1 viral replication and latency. uc002yug.2 potentially enhances HIV-1 viral replication, LTR activity as well as the activation of latent HIV-1 in both cell lines and CD4+ T cells from patients...
February 28, 2018: Journal of Virology
Zheng Wang, Evelyn E Gurule, Timothy P Brennan, Jeffrey M Gerold, Kyungyoon J Kwon, Nina N Hosmane, Mithra R Kumar, Subul A Beg, Adam A Capoferri, Stuart C Ray, Ya-Chi Ho, Alison L Hill, Janet D Siliciano, Robert F Siliciano
The latent reservoir for HIV-1 in resting CD4+ T cells is a major barrier to cure. Several lines of evidence suggest that the latent reservoir is maintained through cellular proliferation. Analysis of this proliferative process is complicated by the fact that most infected cells carry defective proviruses. Additional complications are that stimuli that drive T cell proliferation can also induce virus production from latently infected cells and productively infected cells have a short in vivo half-life. In this ex vivo study, we show that latently infected cells containing replication-competent HIV-1 can proliferate in response to T cell receptor agonists or cytokines that are known to induce homeostatic proliferation and that this can occur without virus production...
February 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
Kamelia R Stanoeva, André König, Asami Fukuda, Yoko Kawanami, Takeo Kuwata, Yorifumi Satou, Shuzo Matsushita
BACKGROUND: Understanding HIV persistence in treated patients is an important milestone towards drug-free control. We aimed to analyze total HIV DNA dynamics and influencing factors in Japanese patients who received more than a decade of suppressive antiretroviral treatment. METHODS: A retrospective study including clinical records and 840 PBMC samples (mean 14 samples/patient) for 59 patients (92% male) was performed. Subjects were divided into two groups: with and without hematological co-morbidity (mainly hemophilia) plus HCV co-infection...
February 23, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
M Echchakery, J Nieto, S Boussaa, N El Fajali, S Ortega, K Souhail, H Aajly, C Chicharro, E Carrillo, J Moreno, A Boumezzough
In Morocco, visceral leishmaniasis (VL) is a parasitic disease caused by the flagellated protozoan parasite Leishmania infantum. L. infantum is transmitted by the bite of female phlebotomine sandflies, and its main reservoir hosts are domestic dogs. Asymptomatic infection with L. infantum is more frequent than clinically apparent disease. In HIV-infected patients, the risk of clinical VL is increased due to immunosuppression that may reactivate latent infections. However, coinfected subjects do not necessarily develop VL and may remain as asymptomatic carriers depending on their immune status...
February 24, 2018: Parasitology Research
Jin Gohda, Kazuo Suzuki, Kai Liu, Xialin Xie, Hiroaki Takeuchi, Jun-Ichiro Inoue, Yasushi Kawaguchi, Takaomi Ishida
HIV-1 latent reservoirs harbouring silenced but replication-competent proviruses are a major obstacle against viral eradication in infected patients. The "shock and kill" strategy aims to reactivate latent provirus with latency reversing agents (LRAs) in the presence of antiretroviral drugs, necessitating the development of effective and efficient LRAs. We screened a chemical library for potential LRAs and identified two dual Polo-like kinase (PLK)/bromodomain inhibitors, BI-2536 and BI-6727 (volasertib), which are currently undergoing clinical trials against various cancers...
February 23, 2018: Scientific Reports
Dionysios C Watson, Eirini Moysi, Antonio Valentin, Cristina Bergamaschi, Santhi Devasundaram, Sotirios P Fortis, Jenifer Bear, Elena Chertova, Julian Bess, Ray Sowder, David J Venzon, Claire Deleage, Jacob D Estes, Jeffrey D Lifson, Constantinos Petrovas, Barbara K Felber, George N Pavlakis
B cell follicles in secondary lymphoid tissues represent an immune privileged sanctuary for AIDS viruses, in part because cytotoxic CD8+ T cells are mostly excluded from entering the follicles that harbor infected T follicular helper (TFH) cells. We studied the effects of native heterodimeric IL-15 (hetIL-15) treatment on uninfected rhesus macaques and on macaques that had spontaneously controlled SHIV infection to low levels of chronic viremia. hetIL-15 increased effector CD8+ T lymphocytes with high granzyme B content in blood, mucosal sites and lymph nodes, including virus-specific MHC-peptide tetramer+ CD8+ cells in LN...
February 2018: PLoS Pathogens
Michelle A DeVost, Matthew R Beymer, Robert E Weiss, Chelsea L Shover, Robert K Bolan
BACKGROUND: Gay, bisexual, and other men who have sex with men (MSM) face higher rates of sexually transmitted infections (STIs) than the general population. The association between venues where sexual partners are met and STI transmission is dynamic and poorly understood, especially among those who use geosocial networking (GSN) apps. This study aimed to determine whether there is a difference in STI incidence between MSM who met their last sexual partner through a GSN app and MSM who met their last partner via other venues...
November 29, 2017: Sexually Transmitted Diseases
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