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https://www.readbyqxmd.com/read/28447329/immune-response-against-salmonella-enteritidis-is-unsettled-by-hiv-infection
#1
Maira Costa Cacemiro, Milena Sobral Espíndola, Leonardo Judson Galvão-Lima, Luana Silva Soares, Caroline Fontanari, Marco Aurélio Prata, Fábio Campioni, Juliana Pfrimer Falcão, Valdes Roberto Bollela, Fabiani Gai Frantz
The human immunodeficiency virus (HIV) is responsible for more than 2 million new infections per year and opportunistic infections such as Salmonella spp. Gastroenteritis is an important cause of mortality and morbidity in developing countries. Monocytes and macrophages play a critical role in the innate immune response against bacterial infections. However during HIV infection the virus can infect these cells and although they are more resistant to the cytopathic effects, they represent an important viral reservoir in these patients...
April 27, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28446770/instability-of-8e5-calibration-standard-revealed-by-digital-pcr-risks-inaccurate-quantification-of-hiv-dna-in-clinical-samples-by-qpcr
#2
Eloise Busby, Alexandra S Whale, R Bridget Ferns, Paul R Grant, Gary Morley, Jonathan Campbell, Carole A Foy, Eleni Nastouli, Jim F Huggett, Jeremy A Garson
Establishing a cure for HIV is hindered by the persistence of latently infected cells which constitute the viral reservoir. Real-time qPCR, used for quantification of this reservoir by measuring HIV DNA, requires external calibration; a common choice of calibrator is the 8E5 cell line, which is assumed to be stable and to contain one HIV provirus per cell. In contrast, digital PCR requires no external calibration and potentially provides 'absolute' quantification. We compared the performance of qPCR and dPCR in quantifying HIV DNA in 18 patient samples...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28437703/antiviral-treatment-strategies-based-on-gene-silencing-and-genome-editing
#3
REVIEW
Roger Badia, Ester Ballana, José A Esté, Eva Riveira-Muñoz
The ability of some viruses to establish latently infected chronic reservoirs that escape to immune control becomes a major roadblock that impedes the cure of these infections. Therefore, new alternatives are needed to pursuit the eradication of viral persistent infections. Gene silencing technologies are in constant evolution and provide an outstanding sequence specificity that allows targeting any coding sequence of interest. Here we provide an overview of the development of gene silencing technologies ranging from initially RNA interference to the recently developed CRISPR/Cas9 and their potential as new antiviral strategies focusing on the eradication of HIV...
April 21, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28435692/a-cd3-cd28-microbead-based-hiv-1-viral-outgrowth-assay
#4
EDITORIAL
Yury V Kuzmichev, Rebecca T Veenhuis, Christopher W Pohlmeyer, Caroline C Garliss, Victoria Ek Walker-Sperling, Joel N Blankson
AIMS: Latently infected resting CD4 T cells represent a major barrier to HIV-1 eradication efforts. The standard assays used for measuring this reservoir induce activation of resting CD4 T cells with either phytohaemagglutinin (PHA) with irradiated feeder cells, or with anti-CD3 antibodies. We designed a study to compare the sensitivity of a new assay (based on the stimulation of CD4 T cells with anti-CD3 and anti-CD28 coated microbeads) with that of the traditional PHA- and feeder-based viral outgrowth assay...
April 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/28435691/interrupting-antiretroviral-treatment-in-hiv-cure-research-scientific-and-ethical-considerations
#5
EDITORIAL
Samual A Garner, Stuart Rennie, Jintanat Ananworanich, Karine Dube, David M Margolis, Jeremy Sugarman, Randall Tressler, Adam Gilbertson, Liza Dawson
Over the past several years there has been intense activity directed at the possibility of achieving remission or eradication of HIV infection. Current assays for the measurement of latent HIV are insufficient to demonstrate complete clearance of replication-competent HIV. Therefore, the ultimate test for assessing whether investigational interventions have resulted in HIV remission or eradication is to interrupt standard antiretroviral therapy (ART) in a carefully controlled clinical trial setting. These procedures, known as analytic treatment interruptions (ATIs), raise important scientific and ethical questions...
April 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/28431490/new-challenges-in-therapeutic-vaccines-against-hiv-infection
#6
Lorna Leal, Constanza Lucero, Josep M Gatell, Teresa Gallart, Montserrat Plana, Felipe García
There is a growing interest in developing curative strategies for HIV infection. Therapeutic vaccines are one of the most promising approaches. We will review the current knowledge and the new challenges in this research field. Areas covered: PubMed and ClinicalTrial.gov databases were searched to review the progress and prospects for clinical development of immunotherapies aimed to cure HIV infection. Dendritic cells (DC)-based vaccines have yielded the best results in the field. However, major immune-virologic barriers may hamper current vaccine strategies...
April 21, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28426825/levels-of-hiv-1-persistence-on-antiretroviral-therapy-are-not-associated-with-markers-of-inflammation-or-activation
#7
Rajesh T Gandhi, Deborah K McMahon, Ronald J Bosch, Christina M Lalama, Joshua C Cyktor, Bernard J Macatangay, Charles R Rinaldo, Sharon A Riddler, Evelyn Hogg, Catherine Godfrey, Ann C Collier, Joseph J Eron, John W Mellors
Antiretroviral therapy (ART) reduces levels of HIV-1 and immune activation but both can persist despite clinically effective ART. The relationships among pre-ART and on-ART levels of HIV-1 and activation are incompletely understood, in part because prior studies have been small or cross-sectional. To address these limitations, we evaluated measures of HIV-1 persistence, inflammation, T cell activation and T cell cycling in a longitudinal cohort of 101 participants who initiated ART and had well-documented sustained suppression of plasma viremia for a median of 7 years...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28426533/hiv-dna-content-in-different-cd4-t-cell-subsets-correlates-with-cd4-cd8-ratio-or-length-of-efficient-treatment
#8
Lara Gibellini, Simone Pecorini, Sara de Biasi, Elena Bianchini, Margherita Digaetano, Marcello Pinti, Gianluca Carnevale, Vanni Borghi, Giovanni Guaraldi, Cristina Mussini, Andrea Cossarizza, Milena Nasi
OBJECTIVES: HIV establishes a latent infection at different degrees within naïve (TN) or central (TCM) and effector memory (TEM) CD4+ T cell. Studying patients in whom HIV production was suppressed by combined antiretroviral therapy (cART), our main aim was to find which factors are related or can influence intracellular viral reservoir in different CD4+ T cell subsets. METHODS: We enrolled 32 HIV+ patients successfully treated for > 2 years, with a CD4+ T cell count > 500 cells/μL and plasma viremia undetectable from at least one year...
April 19, 2017: AIDS
https://www.readbyqxmd.com/read/28424694/immune-responses-in-the-central-nervous-system-are-anatomically-segregated-in-a-non-human-primate-model-of-human-immunodeficiency-virus-infection
#9
Barbara Tavano, Vicky Tsipouri, Gareth A D Hardy, Caroline M Royle, Michael R Keegan, Dietmar Fuchs, Steven Patterson, Neil Almond, Neil Berry, Claire Ham, Deborah Ferguson, Adriano Boasso
The human immunodeficiency virus (HIV) accesses the central nervous system (CNS) early during infection, leading to HIV-associated cognitive impairment and establishment of a viral reservoir. Here, we describe a dichotomy in inflammatory responses in different CNS regions in simian immunodeficiency virus (SIV)-infected macaques, a model for HIV infection. We found increased expression of inflammatory genes and perivascular leukocyte infiltration in the midbrain of SIV-infected macaques. Conversely, the frontal lobe showed downregulation of inflammatory genes associated with interferon-γ and interleukin-6 pathways, and absence of perivascular cuffing...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28423333/hunting-down-the-hiv-1-reservoir-a-starring-role-for-antibodies
#10
Hugo Mouquet
The persistence of viruses "hidden" in a reservoir of latently infected CD4(+) T cells under antiretroviral therapy is the major obstacle to an HIV-1 cure. Recently published in Nature, two seminal studies from Descours et al. (2017) and Nishimura et al. (2017) bring hope for tracking and possibly eradicating the HIV-1 reservoir.
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28422792/progress-in-hiv-1-antibody-research-using-humanized-mice
#11
Henning Gruell, Florian Klein
PURPOSE OF REVIEW: Recent discoveries of highly potent broadly HIV-1 neutralizing antibodies provide new opportunities to successfully prevent, treat, and potentially cure HIV-1 infection. To test their activity in vivo, humanized mice have been shown to be a powerful model and were used to investigate antibody-mediated prevention and therapy approaches. In this review, we will summarize recent findings in humanized mice that have informed on the potential use of broadly neutralizing antibodies targeting HIV-1 in humans...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28414780/sensitive-quantification-of-the-hiv-1-reservoir-in-gut-associated-lymphoid-tissue
#12
Sara Morón-López, Maria C Puertas, Cristina Gálvez, Jordi Navarro, Anna Carrasco, Maria Esteve, Josep Manyé, Manel Crespo, Maria Salgado, Javier Martinez-Picado
BACKGROUND: The implementation of successful strategies to achieve an HIV cure has become a priority in HIV research. However, the current location and size of HIV reservoirs is still unknown since there are limited tools to evaluate HIV latency in viral sanctuaries such as gut-associated lymphoid tissue (GALT). As reported in the so called "Boston Patients", despite undetectable levels of proviral HIV-1 DNA in blood and GALT, viral rebound happens in just few months after ART interruption...
2017: PloS One
https://www.readbyqxmd.com/read/28413625/hiv-associated-neurocognitive-disorders-recent-advances-in-pathogenesis-biomarkers-and-treatment
#13
REVIEW
Antonia Carroll, Bruce Brew
HIV-associated neurocognitive disorders (HAND) remain prevalent despite plasma viral suppression by antiretroviral agents. In fact, the prevalence of milder subtypes of cognitive impairment is increasing. Neuropsychologic testing remains the "gold standard" of diagnosis; however, this is time consuming and costly in a resource-poor environment. Recently developed screening tools, such as CogState and the revised HIV dementia scale, have very good sensitivity and specificity in the more severe stages of HAND...
2017: F1000Research
https://www.readbyqxmd.com/read/28412523/progenitor-strain-introduction-of-mycobacterium-bovis-at-the-wildlife-livestock-interface-can-lead-to-clonal-expansion-of-the-disease-in-a-single-ecosystem
#14
Anzaan Dippenaar, Sven David Charles Parsons, Michele Ann Miller, Tiny Hlokwe, Nicolaas Claudius Gey van Pittius, Sabir Abdu Adroub, Abdallah Musa Abdallah, Arnab Pain, Robin Mark Warren, Anita Luise Michel, Paul David van Helden
Mycobacterium bovis infects multiple wildlife species and domesticated cattle across South Africa, and negatively impacts on livestock trade and movement of wildlife for conservation purposes. M. bovis infection was first reported in the Kruger National Park (KNP) in South Africa during the 1990s, and has since spread to infect numerous animal host species throughout the park and across South Africa. Whole genome sequencing data of 17 M. bovis isolates were analyzed to investigate the genomic diversity among M...
April 13, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28405607/chemoattractant-mediated-leukocyte-trafficking-enables-hiv-dissemination-from-the-genital-mucosa
#15
Maud Deruaz, Thomas T Murooka, Sophina Ji, Marc A Gavin, Vladimir D Vrbanac, Judy Lieberman, Andrew M Tager, Thorsten R Mempel, Andrew D Luster
HIV vaginal transmission accounts for the majority of newly acquired heterosexual infections. However, the mechanism by which HIV spreads from the initial site of viral entry at the mucosal surface of the female genital tract to establish a systemic infection of lymphoid and peripheral tissues is not known. Once the virus exits the mucosa it rapidly spreads to all tissues, leading to CD4(+) T cell depletion and the establishment of a viral reservoir that cannot be eliminated with current treatments. Understanding the molecular and cellular requirements for viral dissemination from the genital tract is therefore of great importance, as it could reveal new strategies to lengthen the window of opportunity to target the virus at its entry site in the mucosa where it is the most vulnerable and thus prevent systemic infection...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28401492/the-alphabet-soup-of-hiv-reservoir-markers
#16
REVIEW
Radwa R Sharaf, Jonathan Z Li
PURPOSE OF REVIEW: Despite the success of antiretroviral therapy in suppressing HIV, life-long therapy is required to avoid HIV reactivation from long-lived viral reservoirs. Currently, there is intense interest in searching for therapeutic interventions that can purge the viral reservoir to achieve complete remission in HIV patients off antiretroviral therapy. The evaluation of such interventions relies on our ability to accurately and precisely measure the true size of the viral reservoir...
April 2017: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/28399056/the-nasopharyngeal-microbiota-of-children-with-respiratory-infections-in-botswana
#17
Matthew S Kelly, Michael G Surette, Marek Smieja, Jeffrey M Pernica, Laura Rossi, Kathy Luinstra, Andrew P Steenhoff, Kristen A Feemster, David M Goldfarb, Tonya Arscott-Mills, Sefelani Boiditswe, Ikanyeng Rulaganyang, Charles Muthoga, Letang Gaofiwe, Tiny Mazhani, John F Rawls, Coleen K Cunningham, Samir S Shah, Patrick C Seed
BACKGROUND: Nearly half of child pneumonia deaths occur in sub-Saharan Africa. Microbial communities in the nasopharynx are a reservoir for pneumonia pathogens and remain poorly described in African children. METHODS: Nasopharyngeal swabs were collected from children with pneumonia (N=204), children with upper respiratory infection symptoms (N=55), and healthy children (N=60) in Botswana between April 2012 and April 2014. We sequenced the V3 region of the bacterial 16S ribosomal RNA gene and used partitioning around medoids to cluster samples into microbiota biotypes...
April 10, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28395180/total-cellular-hiv-1-dna-decreases-after-switching-to-raltegravir-based-regimens-in-patients-with-suppressed-hiv-1-rna
#18
Barbara Rossetti, Genny Meini, Claudia Bianco, Silvia Lamonica, Annalisa Mondi, Simone Belmonti, Iuri Fanti, Nicoletta Ciccarelli, Simona Di Giambenedetto, Maurizio Zazzi, Andrea De Luca
BACKGROUND: The integrase inhibitor raltegravir has been used to intensify antiretroviral therapy in patients with undetectable plasma HIV-1RNA, resulting in variable perturbation of HIV-1 nucleic acids levels in peripheral blood. OBJECTIVES: We aimed at monitoring residual plasma HIV-1RNA and total cellular HIV-1DNA in virologically suppressed patients switching to raltegravir-based regimens. STUDY DESIGN: Fifty-eight subjects on protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens, with plasma HIV-1RNA levels <40 copies/ml for ≥6 months and CD4 counts >200cells/μl for ≥12 months were enrolled...
March 23, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28388353/deficiency-in-dna-damage-response-a-new-characteristic-of-cells-infected-with-latent-hiv-1
#19
Dorota Piekna-Przybylska, Gaurav Sharma, Sanjay B Maggirwar, Robert A Bambara
Viruses can interact with host cell molecules responsible for the recognition and repair of DNA lesions, resulting in dysfunctional DNA damage response (DDR). Cells with inefficient DDR are more vulnerable to therapeutic approaches that target DDR, thereby raising DNA damage to a threshold that triggers apoptosis. Here, we demonstrate that 2 Jurkat-derived cell lines with incorporated silent HIV-1 provirus show increases in DDR signaling that responds to formation of double strand DNA breaks (DSBs). We found that phosphorylation of histone H2AX on Ser139 (gamma-H2AX), a biomarker of DSBs, and phosphorylation of ATM at Ser1981, Chk2 at Thr68, and p53 at Ser15, part of signaling pathways associated with DSBs, are elevated in these cells...
April 7, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28387147/tyrosine-kinase-inhibitors-potential-use-and-safety-considerations-in-hiv-1-infection
#20
Mayte Coiras, Juan Ambrosioni, Francisco Cervantes, José M Miró, José Alcamí
Infection caused by HIV-1 is nowadays a chronic disease due to a highly efficient antiretroviral treatment that is nevertheless, unable to eliminate the virus from the organism. New strategies are necessary in order to impede the formation of the viral reservoirs, responsible for the failure of the antiretroviral treatment to cure the infection. Areas covered: The purpose of this review is to discuss the possibility of using tyrosine kinase inhibitors (TKIs) for the treatment of HIV-1 infection. These inhibitors are successfully used in patients with distinct cancers such as chronic myeloid leukemia...
April 7, 2017: Expert Opinion on Drug Safety
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