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HIV pathogenesis

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https://www.readbyqxmd.com/read/27922852/hiv-associated-changes-in-the-enteric-microbial-community-potential-role-in-loss-of-homeostasis-and-development-of-systemic-inflammation
#1
David B Gootenberg, Jeffrey M Paer, Jesus-Mario Luevano, Douglas S Kwon
PURPOSE OF REVIEW: Despite HIV therapy advances, average life expectancy in HIV-infected individuals on effective treatment is significantly decreased relative to uninfected persons, largely because of increased incidence of inflammation-related diseases, such as cardiovascular disease and renal dysfunction. The enteric microbial community could potentially cause this inflammation, as HIV-driven destruction of gastrointestinal CD4 T cells may disturb the microbiota-mucosal immune system balance, disrupting the stable gut microbiome and leading to further deleterious host outcomes...
December 2, 2016: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/27912079/a-humanized-mouse-model-for-hiv-2-infection-and-efficacy-testing-of-a-single-pill-triple-drug-combination-anti-retroviral-therapy
#2
Shuang Hu, Charles Preston Neff, Dipu Mohan Kumar, Yuichiro Habu, Sarah R Akkina, Takahiro Seki, Ramesh Akkina
While HIV-2 is a causative agent for AIDS in addition to the better studied HIV-1, there is currently no suitable animal model for experimental studies for HIV-2 infection and evaluating promising drugs in vivo. Here we evaluated humanized mice for their susceptibility to HIV-2 infection and tested a single-pill three drug formulation of anti-retrovirals (NRTIs abacavir and lamivudine, integrase inhibitor dolutegravir) (trade name, Triumeq(R)). Our results showed that hu-mice are susceptible to HIV-2 infection showing persistent viremia and CD4 T cell loss, key hallmarks of AIDS pathogenesis...
November 29, 2016: Virology
https://www.readbyqxmd.com/read/27912071/classical-and-alternative-macrophages-have-impaired-function-during-acute-and-chronic-hiv-1-infection
#3
Leonardo J Galvão-Lima, Milena S Espíndola, Luana S Soares, Fabiana A Zambuzi, Maira Cacemiro, Caroline Fontanari, Valdes R Bollela, Fabiani G Frantz
OBJECTIVES: Three decades after HIV recognition and its association with AIDS development, many advances have emerged - especially related to prevention and treatment. Undoubtedly, the development of Highly Active Antiretroviral Therapy (HAART) dramatically changed the future of the syndrome that we know today. In the present study, we evaluate the impact of HAART on macrophage function and its relevance to HIV pathogenesis. METHODS: PBMCs were isolated from blood samples and monocytes (CD14+ cells) were purified...
November 29, 2016: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27909244/cd4-down-regulation-by-hiv-1-nef-reveals-distinct-roles-for-%C3%AE-1-and-%C3%AE-2-subunits-of-ap-1-complex-in-protein-trafficking
#4
Lucas A Tavares, Eulália M L da Silva, Mara E da Silva-Januário, Yunan C Januário, Julianne V de Cavalho, Érika S Czernisz, Gonzalo A Mardones, Luis L P daSilva
The HIV accessory protein Nef is a major determinant of viral pathogenesis that facilitates viral particle release, prevents viral antigen presentation and increases infectivity of new virus particles. These functions of Nef involve its ability to remove specific host proteins from the surface of infected cells, including the CD4 receptor. Nef binds to the adaptor protein 2 (AP-2) and CD4 in clathrin-coated pits, forcing CD4 internalization and subsequent target to lysosomes. Herein, we report that this lysosomal targeting requires a variant of the AP-1 comprising the isoform 2 of γ-adaptin...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27906073/gut-barrier-structure-mucosal-immunity-and-intestinal-microbiota-in-the-pathogenesis-and-treatment-of-hiv-infection
#5
REVIEW
Camilla Tincati, Daniel C Douek, Giulia Marchetti
Over the past 10 years, extensive work has been carried out in the field of microbial translocation in HIV infection, ranging from studies on its clinical significance to investigations on its pathogenic features. In the present work, we review the most recent findings on this phenomenon, focusing on the predictive role of microbial translocation in HIV-related morbidity and mortality, the mechanisms by which it arises and potential therapeutic approaches. From a clinical perspective, current work has shown that markers of microbial translocation may be useful in predicting clinical events in untreated HIV infection, while conflicting data exist on their role in cART-experienced subjects, possibly due to the inclusion of extremely varied patient populations in cohort studies...
April 11, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27906032/infection-of-rhesus-macaques-with-a-pool-of-simian-immunodeficiency-virus-with-the-envelope-genes-from-acute-hiv-1-infections
#6
Kendall C Krebs, Meijuan Tian, Mohammed Asmal, Binhua Ling, Kenneth Nelson, Kenneth Henry, Richard Gibson, Yuejin Li, Weining Han, Robin J Shattock, Ronald S Veazey, Norman Letvin, Eric J Arts, Yong Gao
BACKGROUND: New simian-human immunodeficiency chimeric viruses with an HIV-1 env (SHIVenv) are critical for studies on HIV pathogenesis, vaccine development, and microbicide testing. Macaques are typically exposed to single CCR5-using SHIVenv which in most instances does not reflect the conditions during acute/early HIV infection (AHI) in humans. Instead of individual and serial testing new SHIV constructs, a pool of SHIVenv_B derived from 16 acute HIV-1 infections were constructed using a novel yeast-based SHIV cloning approach and then used to infect macaques...
November 25, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27906007/what-happens-to-cardiovascular-system-behind-the-undetectable-level-of-hiv-viremia
#7
REVIEW
Gabriella d'Ettorre, Giancarlo Ceccarelli, Paolo Pavone, Pietro Vittozzi, Gabriella De Girolamo, Ivan Schietroma, Sara Serafino, Noemi Giustini, Vincenzo Vullo
Despite the combined antiretroviral therapy has improved the length and quality of life of HIV infected patients, the survival of these patients is always decreased compared with the general population. This is the consequence of non-infectious illnesses including cardio vascular diseases. In fact large studies have indicated an increased risk of coronary atherosclerotic disease, myocardial infarction even in HIV patients on cART. In HIV infected patients several factors may contribute to the pathogenesis of cardiovascular problems: life-style, metabolic parameters, genetic predisposition, viral factors, immune activation, chronic inflammation and side effects of antiretroviral therapy...
April 27, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27905556/cellular-aspartyl-proteases-promote-the-unconventional-secretion-of-biologically-active-hiv-1-matrix-protein-p17
#8
Francesca Caccuri, Maria Luisa Iaria, Federica Campilongo, Kristen Varney, Alessandro Rossi, Stefania Mitola, Silvia Schiarea, Antonella Bugatti, Pietro Mazzuca, Cinzia Giagulli, Simona Fiorentini, Wuyuan Lu, Mario Salmona, Arnaldo Caruso
The human immune deficiency virus type 1 (HIV-1) matrix protein p17 (p17), although devoid of a signal sequence, is released by infected cells and detected in blood and in different organs and tissues even in HIV-1-infected patients undergoing successful combined antiretroviral therapy (cART). Extracellularly, p17 deregulates the function of different cells involved in AIDS pathogenesis. The mechanism of p17 secretion, particularly during HIV-1 latency, still remains to be elucidated. A recent study showed that HIV-1-infected cells can produce Gag without spreading infection in a model of viral latency...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27903799/cxcr6-mediated-sivagmsab-entry-into-sabaeus-african-green-monkey-lymphocytes-implicates-widespread-use-of-non-ccr5-pathways-in-natural-host-infections
#9
Katherine S Wetzel, Yanjie Yi, Sarah T C Elliott, Dino Romero, Beatrice Jacquelin, Beatrice H Hahn, Michaela Muller-Trutwin, Cristian Apetrei, Ivona Pandrea, Ronald G Collman
: African green monkeys (AGM) and sooty mangabeys (SM) are well-studied natural hosts of SIV, which do not progress to AIDS when infected with their species-specific viruses. SIV natural hosts express very low levels of the canonical entry coreceptor CCR5, and recent studies have shown that CCR5 is dispensable for SIV infection of SM in vivo, and blocking CCR5 does not prevent ex vivo infection of PBMC from SM or vervet AGM. In both hosts, CXCR6 is an efficient entry pathway in vitro...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27902330/simian-immunodeficiency-virus-sivmac239-infection-and-simian-human-immunodeficiency-virus-shiv89-6p-infection-result-in-progression-to-aids-in-cynomolgus-macaques-from-asian-country-origin
#10
Tomotaka Okamura, Yusuke Tsujimura, Shogo Soma, Ichiro Takahashi, Kazuhiro Matsuo, Yasuhiro Yasutomi
Simian immunodeficiency virus (SIV) infection models in cynomolgus macaques are important for analysis of the pathogenesis of immunodeficiency virus and for studies on the efficacy of new vaccine candidates. However, very little is known about the pathogenesis of SIV or simian human immunodeficiency virus (SHIV) in cynomolgus macaques from different Asian country origins. In the present study, we analyzed the infectivity and pathogenicity of CCR5-tropic SIVmac and those of dual-tropic SHIV89.6P inoculated in cynomolgus macaques of Indonesia, Malaysia or Philippines origin...
October 21, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27891132/impact-of-chronic-hiv-siv-infection-on-t-follicular-helper-cell-subsets-and-germinal-center-homeostasis
#11
REVIEW
Stéphanie Graff-Dubois, Angeline Rouers, Arnaud Moris
The discovery of broad and potent HIV-1 neutralizing antibodies (bNAbs) has renewed optimism for developing an effective vaccine against HIV-1. The generation of most bNAbs requires multiple rounds of B cell receptor affinity maturation, suggesting a crucial role of follicular helper T (Tfh) cells in their production. However, less than 1% of HIV-infected patients develop bNAbs that arise late in the course of infection, indicating probable Tfh and B cell dysfunctions in this context. Since the last few years, many studies have characterized Tfh cells from lymph nodes and spleen of HIV-infected individuals and SIV-infected macaques...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27887644/copenhagen-comorbidity-in-hiv-infection-cocomo-study-a-study-protocol-for-a-longitudinal-non-interventional-assessment-of-non-aids-comorbidity-in-hiv-infection-in-denmark
#12
Andreas Ronit, Judith Haissman, Ditte Marie Kirkegaard-Klitbo, Thomas Skårup Kristensen, Anne-Mette Lebech, Thomas Benfield, Jan Gerstoft, Henrik Ullum, Lars Køber, Andreas Kjær, Klaus Kofoed, Jørgen Vestbo, Børge Nordestgaard, Jens Lundgren, Susanne Dam Nielsen
BACKGROUND: Modern combination antiretroviral therapy (cART) has improved survival for people living with HIV (PLWHIV). Non-AIDS comorbidities have replaced opportunistic infections as leading causes of mortality and morbidity, and are becoming a key health concern as this population continues to age. The aim of this study is to estimate the prevalence and incidence of non-AIDS comorbidity among PLWHIV in Denmark in the cART era and to determine risk factors contributing to the pathogenesis...
November 26, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27882942/emerging-roles-of-extracellular-vesicles-in-neurodegenerative-disorders-focus-on-hiv-associated-neurological-complications
#13
REVIEW
Guoku Hu, Lu Yang, Yu Cai, Fang Niu, Frank Mezzacappa, Shannon Callen, Howard S Fox, Shilpa Buch
Exosomes are membrane-enriched extracellular vesicles with a proposed diameter in the range of 30-100 nm. They are released during both normal homeostasis as well as under pathological conditions by most cell types. In recent years, there has been robust interest in the study of these vesicles as conduits for the delivery of information between cells in both analogous as well as disparate tissues. Their ability to transport specialized cargo including signaling mediators, proteins, messenger RNA and miRNAs characterizes these vesicles as primary facilitators of cell-to-cell communication and regulation...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27880829/interleukin-15-il-15-strongly-correlates-with-increasing-hiv-1-viremia-and-markers-of-inflammation
#14
Sanjay Swaminathan, Ju Qiu, Adam W Rupert, Zonghui Hu, Jeanette Higgins, Robin L Dewar, Randy Stevens, Catherine A Rehm, Julia A Metcalf, Brad T Sherman, Michael W Baseler, H Clifford Lane, Tomozumi Imamichi
OBJECTIVE: IL-15 has been postulated to play an important role in HIV-1 infection, yet there are conflicting reports regarding its expression levels in these patients. We sought to measure the level of IL-15 in a large, well characterised cohort of HIV-1 infected patients and correlate this with well known markers of inflammation, including CRP, D-dimer, sCD163 and sCD14. DESIGN AND METHODS: IL-15 levels were measured in 501 people (460 patients with HIV-1 infection and 41 uninfected controls)...
2016: PloS One
https://www.readbyqxmd.com/read/27872210/distribution-and-activation-of-cd8-t-cells-in-the-duodenal-mucosa-before-and-after-hiv-seroconversion
#15
Kristina Allers, Andreas Puyskens, Hans-Jörg Epple, Dirk Schürmann, Jörg Hofmann, Verena Moos, Thomas Schneider
CD8(+) T cells in the intestinal mucosa influence the HIV-associated pathogenesis, but little is known about the dynamics of mucosal CD8(+) T cell counts and activation of these cells during the course of infection. In this study, mucosal CD8(+) T cells in the duodenum were studied at different stages of HIV infection, starting from the seronegative phase. In seronegative acute HIV infection, CD8(+) T cell counts increased in the epithelium, but not in the lamina propria. Infiltration of the lamina propria by peripherally expanded CD8(+) T cells was observed after seroconversion...
November 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27870882/immune-activation-at-sites-of-hiv-tb-co-infection-contributes-to-the-pathogenesis-of-hiv-1-disease
#16
Qinglai Meng, Ismail Sayin, David H Canaday, Harriet Mayanja-Kizza, Joy Baseke, Zahra Toossi
Systemic immune activation is critical to the pathogenesis of HIV-1 disease, and is accentuated in HIV/TB co-infected patients. The contribution of immune activation at sites of HIV/TB co-infection to viral activity, CD4 T cell count, and productive HIV-1 infection remain unclear. In this study, we measured markers of immune activation both in pleural fluid and plasma, and in T cells in pleural fluid mononuclear cell (PFMC) and peripheral blood mononuclear cell (PBMC) in HIV/TB co-infected subjects. The relationship between soluble and T cell activation markers with viral load in pleural fluid and blood CD4 T cell count were assessed...
2016: PloS One
https://www.readbyqxmd.com/read/27867916/impact-of-human-immunodeficiency-virus-in-the-pathogenesis-and-outcome-of-patients-with-glioblastoma-multiforme
#17
Winward Choy, Carlito Lagman, Seung J Lee, Timothy T Bui, Michael Safaee, Isaac Yang
BACKGROUND: Improvement in antiviral therapies have been accompanied by an increased frequency of non-Acquired Immune Deficiency Syndrome (AIDS) defining malignancies, such as glioblastoma multiforme. Here, we investigated all reported cases of human immunodeficiency virus (HIV)-positive patients with glioblastoma and evaluated their clinical outcomes. A comprehensive review of the molecular pathogenetic mechanisms underlying glioblastoma development in the setting of HIV/AIDS is provided...
October 2016: Brain Tumor Research and Treatment
https://www.readbyqxmd.com/read/27867372/overlapping-regions-in-hiv-1-genome-act-as-potential-sites-for-host-virus-interaction
#18
Deeya Saha, Soumita Podder, Tapash C Ghosh
More than a decade, overlapping genes in RNA viruses became a subject of research which has explored various effect of gene overlapping on the evolution and function of viral genomes like genome size compaction. Additionally, overlapping regions (OVRs) are also reported to encode elevated degree of protein intrinsic disorder (PID) in unspliced RNA viruses. With the aim to explore the roles of OVRs in HIV-1 pathogenesis, we have carried out an in-depth analysis on the association of gene overlapping with PID in 35 HIV1- M subtypes...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27865749/in-vitro-functional-assessment-of-natural-hiv-1-group-m-vpu-sequences-using-a-universal-priming-approach
#19
Asa Rahimi, Gursev Anmole, Maribel Soto-Nava, Tania Escamilla-Gomez, Tristan Markle, Steven W Jin, Guinevere Q Lee, P Richard Harrigan, David R Bangsberg, Jeffrey Martin, Santiago Avila-Rios, Gustavo Reyes-Teran, Mark A Brockman, Zabrina L Brumme
The HIV-1 accessory protein Vpu exhibits high inter- and intra- subtype genetic diversity that may influence Vpu function and possibly contribute to HIV-1 pathogenesis. However, scalable methods to evaluate genotype/phenotype relationships in natural Vpu sequences are limited, particularly those expressing the protein in CD4+ T-cells, the natural target of HIV-1 infection. A major impediment to assay scalability is the extensive genetic diversity within, and immediately upstream of, Vpu's initial 5' coding region, which has necessitated the design of oligonucleotide primers specific for each individual HIV-1 isolate (or subtype)...
November 16, 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/27862500/antibodies-to-h1-histone-from-the-sera-of-hiv-infected-patients-recognize-and-catalyze-site-specific-degradation-of-this-histone
#20
Svetlana V Baranova, Pavel S Dmitrienok, Nikita V Ivanisenko, Valentina N Buneva, Georgy A Nevinsky
Histones and their posttranslational modifications have key roles in chromatin remodeling and gene transcription. Besides intranuclear functions, histones act as damage-associated molecules when they are released into the extracellular space. Administration of histones to animals leads to systemic inflammatory and toxic responses. Autoantibodies with enzymatic activities (abzymes) are distinctive feature of some autoimmune and viral diseases. Electrophoretically and immunologically homogeneous IgGs containing no canonical enzymes were isolated from sera of human immunodeficiency virus-infected patients by chromatography on several affinity sorbents...
November 10, 2016: Journal of Molecular Recognition: JMR
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