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https://www.readbyqxmd.com/read/29052131/merkel-cell-polyomavirus-a-new-dna-virus-associated-with-human-cancer
#1
Margo MacDonald, Jianxin You
Merkel cell polyomavirus (MCPyV or MCV) is a novel human polyomavirus that has been discovered in Merkel cell carcinoma (MCC), a highly aggressive skin cancer. MCPyV infection is widespread in the general population. MCPyV-associated MCC is one of the most aggressive skin cancers, killing more patients than other well-known cancers such as cutaneous T-cell lymphoma and chronic myelogenous leukemia (CML). Currently, however, there is no effective drug for curing this cancer. The incidence of MCC has tripled over the past two decades...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29048512/excellent-treatment-outcomes-in-children-treated-for-tuberculosis-under-routine-operational-conditions-in-cape-town-south-africa
#2
Muhammad Osman, Kevin Lee, Karen Du Preez, Rory Dunbar, Anneke C Hesseling, James A Seddon
Background: Tuberculosis (TB) remains a leading cause of death in children globally. It is recognized that human immunodeficiency virus (HIV) infection increases the risk of developing TB, but our understanding of the impact of HIV on risk of mortality for children treated for TB is limited. We aimed to identify predictors of mortality in children treated for drug-susceptible TB. Methods: A retrospective analysis of all children (<15 years of age) routinely treated between 2005 and 2012 for drug-susceptible TB in Cape Town was conducted using the programmatic electronic TB treatment database...
October 16, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29047415/transgender-women-in-malaysia-in-the-context-of-hiv-and-islam-a-qualitative-study-of-stakeholders-perceptions
#3
Sima Barmania, Syed Mohamed Aljunid
BACKGROUND: Globally, one of the key groups considered to be at high risk of acquiring HIV are transgender women, often a marginalised group. In the Malaysian context there has been a scarcity of published research relating to transgender women, a sensitive issue in a Muslim majority country, where Islam plays an influential role in society. Furthermore, there has been a paucity of research relating to how such issues relate to HIV prevention in transgender women in Malaysia. Thus, the aim of this study is to explore the attitudes of stakeholders involved in HIV prevention policy in Malaysia towards transgender women, given the Islamic context...
October 18, 2017: BMC International Health and Human Rights
https://www.readbyqxmd.com/read/29045906/ctla-4-pd-1-memory-cd4-t-cells-critically-contribute-to-viral-persistence-in-antiretroviral-therapy-suppressed-siv-infected-rhesus-macaques
#4
Colleen S McGary, Claire Deleage, Justin Harper, Luca Micci, Susan P Ribeiro, Sara Paganini, Leticia Kuri-Cervantes, Clarisse Benne, Emily S Ryan, Robert Balderas, Sherrie Jean, Kirk Easley, Vincent Marconi, Guido Silvestri, Jacob D Estes, Rafick-Pierre Sekaly, Mirko Paiardini
Antiretroviral therapy (ART) suppresses viral replication in HIV-infected individuals but does not eliminate the reservoir of latently infected cells. Recent work identified PD-1(+) follicular helper T (Tfh) cells as an important cellular compartment for viral persistence. Here, using ART-treated, SIV-infected rhesus macaques, we show that CTLA-4(+)PD-1(-) memory CD4(+) T cells, which share phenotypic markers with regulatory T cells, were enriched in SIV DNA in blood, lymph nodes (LN), spleen, and gut, and contained replication-competent and infectious virus...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045905/transcriptional-reprogramming-during-effector-to-memory-transition-renders-cd4-t-cells-permissive-for-latent-hiv-1-infection
#5
Liang Shan, Kai Deng, Hongbo Gao, Sifei Xing, Adam A Capoferri, Christine M Durand, S Alireza Rabi, Gregory M Laird, Michelle Kim, Nina N Hosmane, Hung-Chih Yang, Hao Zhang, Joseph B Margolick, Linghua Li, Weiping Cai, Ruian Ke, Richard A Flavell, Janet D Siliciano, Robert F Siliciano
The latent reservoir for HIV-1 in resting memory CD4(+) T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4(+) T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045893/hiv-1-latency-by-transition
#6
Boris Julg, Dan H Barouch
The latent HIV-1 reservoir represents the major barrier for the development of an HIV-1 cure. In this issue of Immunity, Shan et al. (2017) highlight that effector-to-memory transitioning (EMT) CD4(+) T cells are particularly permissive for the establishment of latent HIV-1 infection.
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045830/in%C3%A2-vivo-suppression-of-hiv-rebound-by-didehydro-cortistatin-a-a-block-and-lock-strategy-for-hiv-1-treatment
#7
Cari F Kessing, Christopher C Nixon, Chuan Li, Perry Tsai, Hiroshi Takata, Guillaume Mousseau, Phong T Ho, Jenna B Honeycutt, Mohammad Fallahi, Lydie Trautmann, J Victor Garcia, Susana T Valente
HIV-1 Tat activates viral transcription and limited Tat transactivation correlates with latency establishment. We postulated a "block-and-lock" functional cure approach based on properties of the Tat inhibitor didehydro-Cortistatin A (dCA). HIV-1 transcriptional inhibitors could block ongoing viremia during antiretroviral therapy (ART), locking the HIV promoter in persistent latency. We investigated this hypothesis in human CD4(+) T cells isolated from aviremic individuals. Combining dCA with ART accelerates HIV-1 suppression and prevents viral rebound after treatment interruption, even during strong cellular activation...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29045701/regulatory-t-cells-contribute-to-hiv-1-reservoir-persistence-in-cd4-t-cells-through-camp-dependent-mechanisms-in-humanized-mice-in-vivo
#8
Guangming Li, Jun-Ichi Nunoya, Liang Cheng, Natalia Reszka-Blanco, Li-Chung Tsao, Jerry Jeffrey, Lishan Su
Background: Regulatory T cells (Tregs) suppress T cell immune activation and HIV-1 replication, but the role of Tregs in HIV-1 reservoir persistence is poorly defined. Methods: Tregs were depleted in HIV-1 chronically infected humanized mice by Denileukin Diftitox. Viral replication in lineage cells was determined by p24 expression. HIV-1 RNA and DNA in human cells as well as replication-competent virus producing cells were measured to quantified viral replication and reservoirs...
October 14, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29036618/unsuccessful-treatment-in-pulmonary-tuberculosis-factors-and-a-consequent-predictive-model
#9
Ana Costa-Veiga, Teodoro Briz, Carla Nunes
Background: Cure is particularly valuable in pulmonary cases (PTB), as unsuccessful treatment fuels incidence and resistance to antibiotics. This study aims to identify individual factors of PTB unsuccessful treatment in Portugal and to develop a consequent predictive model. Methods: Using the Portuguese TB surveillance database (SVIG-TB), PTB cases older than 15 years notified from 2000 to 2012 in Continental Portugal were analyzed. Unsuccessful treatment included the WHO categories (failure, default, death and transferred out)...
October 3, 2017: European Journal of Public Health
https://www.readbyqxmd.com/read/29026923/nonhuman-primate-models-for-studies-of-aids-virus-persistence-during-suppressive-combination-antiretroviral-therapy
#10
Gregory Q Del Prete, Jeffrey D Lifson
Nonhuman primate (NHP) models of AIDS represent a potentially powerful component of the effort to understand in vivo sources of AIDS virus that persist in the setting of suppressive combination antiretroviral therapy (cART) and to develop and evaluate novel strategies for more definitive treatment of HIV infection (i.e., viral eradication "cure", or sustained off-cART remission). Multiple different NHP models are available, each characterized by a particular NHP species, infecting virus, and cART regimen, and each with a distinct capacity to recapitulate different aspects of HIV infection...
October 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/29023549/supraphysiologic-control-over-hiv-1-replication-mediated-by-cd8-t-cells-expressing-a-re-engineered-cd4-based-chimeric-antigen-receptor
#11
Rachel S Leibman, Max W Richardson, Christoph T Ellebrecht, Colby R Maldini, Joshua A Glover, Anthony J Secreto, Irina Kulikovskaya, Simon F Lacey, Sarah R Akkina, Yanjie Yi, Farida Shaheen, Jianbin Wang, Keith A Dufendach, Michael C Holmes, Ronald G Collman, Aimee S Payne, James L Riley
HIV is adept at avoiding naturally generated T cell responses; therefore, there is a need to develop HIV-specific T cells with greater potency for use in HIV cure strategies. Starting with a CD4-based chimeric antigen receptor (CAR) that was previously used without toxicity in clinical trials, we optimized the vector backbone, promoter, HIV targeting moiety, and transmembrane and signaling domains to determine which components augmented the ability of T cells to control HIV replication. This re-engineered CAR was at least 50-fold more potent in vitro at controlling HIV replication than the original CD4 CAR, or a TCR-based approach, and substantially better than broadly neutralizing antibody-based CARs...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29022569/syphilis
#12
REVIEW
Rosanna W Peeling, David Mabey, Mary L Kamb, Xiang-Sheng Chen, Justin D Radolf, Adele S Benzaken
Treponema pallidum subspecies pallidum (T. pallidum) causes syphilis via sexual exposure or via vertical transmission during pregnancy. T. pallidum is renowned for its invasiveness and immune-evasiveness; its clinical manifestations result from local inflammatory responses to replicating spirochaetes and often imitate those of other diseases. The spirochaete has a long latent period during which individuals have no signs or symptoms but can remain infectious. Despite the availability of simple diagnostic tests and the effectiveness of treatment with a single dose of long-acting penicillin, syphilis is re-emerging as a global public health problem, particularly among men who have sex with men (MSM) in high-income and middle-income countries...
October 12, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/29022531/survival-of-patients-with-kaposi-s-sarcoma-in-the-south-african-antiretroviral-treatment-era-a-retrospective-cohort-study
#13
M M Sengayi, D Kielkowski, M Egger, L Dreosti, J Bohlius
BACKGROUND: When South Africa (SA) implemented its antiretroviral therapy (ART) programme in 2004, the model for treating HIV-positive Kaposi's sarcoma (KS) patients shifted from symptomatic palliation to potential cure. OBJECTIVE: To evaluate survival and changes over time in AIDS-KS patients treated at a tertiary academic hospital oncology unit (the Steve Biko Academic Hospital medical oncology unit) in Pretoria, SA, in the context of ART availability in SA. METHODS: We conducted a retrospective review of electronic and paper records of KS patients who accessed cancer care between May 2004 and September 2012...
September 22, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/29021399/modelling-of-anti-latency-treatment-in-hiv-what-is-the-optimal-duration-of-anti-retroviral-free-hiv-remission
#14
Deborah Cromer, Mykola Pinkevych, Thomas A Rasmussen, Sharon R Lewin, Stephen J Kent, Miles P Davenport
A number of treatment strategies are currently being developed to promote anti-retroviral free HIV cure or remission. While complete elimination of the HIV reservoir would prevent recurrence of infection, it is not clear how different remission lengths would affect viral rebound and transmission. In this work we use a stochastic model to show that a treatment that achieves a one-year average time to viral remission will still lead to nearly a quarter of subjects experiencing viral rebound within the first three months...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29021396/quiescence-promotes-latent-hiv-infection-and-resistance-to-reactivation-from-latency-with-histone-deacetylase-inhibitors
#15
Mark M Painter, Thomas D Zaikos, Kathleen L Collins
Human immunodeficiency virus type-1 (HIV-1) establishes transcriptionally silent latent infections in many cell types, including resting memory T cells and hematopoietic stem and progenitor cells (HSPCs), which allow the virus to persist in infected individuals despite antiretroviral therapy. Developing in vitro models of HIV-1 latency that recapitulate the characteristics of latently-infected cells in vivo is crucial to identifying and developing effective latency-reversing therapies. HSPCs exist in a quiescent state in vivo, and quiescence is correlated with latent infections in T cells...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29020196/the-risk-and-predictors-of-visceral-leishmaniasis-relapse-in-human-immunodeficiency-virus-coinfected-patients-in-ethiopia-a-retrospective-cohort-study
#16
Charles Abongomera, Ermias Diro, Florian Vogt, Achilleas Tsoumanis, Zelalem Mekonnen, Henok Admassu, Robert Colebunders, Rezika Mohammed, Koert Ritmeijer, Johan van Griensven
Background: East Africa, where Leishmania donovani is prevalent, faces the highest burden world-wide of visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) coinfection. However, data on the risk and predictors of VL relapse are scarce. Such information is vital to target medical follow-up and interventions to those at highest risk. Methods: We conducted a retrospective cohort study at a Médecins Sans Frontières-supported health center in northwest Ethiopia...
July 20, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29019352/hot-news-gene-therapy-with-crispr-cas9-coming-to-age-for-hiv-cure
#17
Vicente Soriano
The huge success of current antiretroviral therapy is mediated by a triple effect: (i) Halting progression to AIDS in infected persons; (ii) reducing the risk of transmission to contacts (treatment as prevention); and (iii) minimizing the risk of HIV acquisition treating uninfected persons at risk (pre-exposure prophylaxis). However, UNAIDS has estimated that only 70% of infected people globally are diagnosed, only 53% are treated, and overall 44% have undetectable viral load, which is the necessary request for ensuring any antiretroviral benefit...
October 11, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/29019351/hot-news-exosomes-as-new-players-in-hiv-pathogenesis-new-data-from-the-ias-2017
#18
Eva Poveda, Michael L Freeman
Exosomes are nanovesicles that can be released into the extracellular medium by different cell types and are considered an important system of intercellular communication. In some instances, on secretion, exosomes break down and release their content into the extracellular space. Alternatively, intact exosomes can interact with other cells and discharge their content directly into the target cell cytoplasm. Exosomes are rich in endosome-associated proteins (i.e., the tetraspanin family) but also carry different molecules in their lumen including proteins, RNAs (i...
October 11, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/29017282/plasma-cytokine-predictors-of-tuberculosis-recurrence-in-antiretroviral-treated-human-immunodeficiency-virus-infected-individuals-from-durban-south-africa
#19
Aida Sivro, Lyle R McKinnon, Nonhlanhla Yende-Zuma, Santhana Gengiah, Natasha Samsunder, Salim S Abdool Karim, Kogieleum Naidoo
Background: Immune correlates of tuberculosis (TB) risk in populations infected with human immunodeficiency virus (HIV) remain understudied, despite HIV being associated with a high burden of TB disease. Here we describe plasma cytokine correlates of TB recurrence in a well-characterized cohort of HIV-infected individuals on antiretroviral therapy (ART) with a history of prior TB cure. Methods: Study participants were drawn from a prospective cohort study initiated at the conclusion of a randomized clinical trial in which individuals presented with untreated HIV infection and active pulmonary TB...
September 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28990680/baseline-ns5a-resistance-associated-substitutions-may-impair-daa-response-in-real-world-hepatitis-c-patients
#20
Itziar Carrasco, Ana Arias, Laura Benítez-Gutiérrez, Gema Lledó, Silvia Requena, Miriam Cuesta, Valentín Cuervas-Mons, Carmen de Mendoza
BACKGROUND: Oral DAA have demonstrated high efficacy as treatment of hepatitis C. However, the presence of resistance-associated substitutions (RAS) at baseline has occasionally been associated with impaired treatment response. Herein, we examined the impact of baseline RAS at the HCV NS5A gene region on treatment response in a real-life setting. METHODS: All hepatitis C patients treated with DAA including NS5A inhibitors at our institution were retrospectively examined...
October 9, 2017: Journal of Medical Virology
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