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https://www.readbyqxmd.com/read/29785584/interferon-free-therapy-in-hepatitis-c-virus-hcv-monoinfected-and-hcv-hiv-coinfected-patients-effect-on-cognitive-function-fatigue-and-mental-health
#1
Felix Kleefeld, Sophie Heller, Patrick Ingiliz, Heiko Jessen, Anders Petersen, Ute Kopp, Antje Kraft, Katrin Hahn
The efficacy and safety of interferon-free therapies for hepatitis C virus (HCV) infection have been reported. Considering the accumulating evidence for a direct central nervous system infection by HCV, we aim to evaluate the effect of direct acting antivirals (DAA) therapy on cognitive function in HCV patients. We conducted a longitudinal analysis of the cognitive performance of 22 patients (8 HCV+, 14 HCV+/HIV+) who completed neuropsychological testing at baseline and at week 12 after DAA therapy. In 20 patients, we analyzed specific attention parameters derived from an experimental testing based on the Theory of Visual Attention (TVA)...
May 21, 2018: Journal of Neurovirology
https://www.readbyqxmd.com/read/29770360/biomarkers-associated-with-death-after-initiating-treatment-for-tuberculosis-and-hiv-in-patients-with-very-low-cd-4-cells
#2
Fred R Sattler, Daniel Chelliah, Xingye Wu, Alejandro Sanchez, Michelle A Kendall, Evelyn Hogg, David Lagat, Umesh Lalloo, Valdilea Veloso, Diane V Havlir, Alan Landay
Background: The risk of short-term death for treatment naive patients dually infected with Mycobacterium tuberculosis and HIV may be reduced by early anti-retroviral therapy. Of those dying, mechanisms responsible for fatal outcomes are unclear. We hypothesized that greater malnutrition and/or inflammation when initiating treatment are associated with an increased risk for death. Methods: We utilized a retrospective case-cohort design among participants of the ACTG A5221 study who had baseline CD4 < 50 cells/mm3 ...
2018: Pathogens & Immunity
https://www.readbyqxmd.com/read/29769566/antiretroviral-drugs-alter-the-content-of-extracellular-vesicles-from-hiv-1-infected-cells
#3
Catherine DeMarino, Michelle L Pleet, Maria Cowen, Robert A Barclay, Yao Akpamagbo, James Erickson, Nicaise Ndembe, Manhattan Charurat, Jibreel Jumare, Sunday Bwala, Peter Alabi, Max Hogan, Archana Gupta, Nicole Noren Hooten, Michele K Evans, Benjamin Lepene, Weidong Zhou, Massimo Caputi, Fabio Romerio, Walter Royal, Nazira El-Hage, Lance A Liotta, Fatah Kashanchi
To date, the most effective treatment of HIV-1 is a combination antiretroviral therapy (cART), which reduces viral replication and reverses pathology. We investigated the effect of cART (RT and protease inhibitors) on the content of extracellular vesicles (EVs) released from HIV-1-infected cells. We have previously shown that EVs contain non-coding HIV-1 RNA, which can elicit responses in recipient cells. In this manuscript, we show that TAR RNA levels demonstrate little change with the addition of cART treatment in cell lines, primary macrophages, and patient biofluids...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769349/hiv-1-activation-of-innate-immunity-depends-strongly-on-the-intracellular-level-of-trex1-and-sensing-of-incomplete-reverse-transcription-products
#4
Swati Kumar, James H Morrison, David Dingli, Eric Poeschla
TREX1 has been reported to degrade cytosolic immune-stimulatory DNA, including viral DNA generated during HIV-1 infection, but the dynamic range of its capacity to suppress innate immune stimulation is unknown and its full role in the viral life cycle remains unclear. A main purpose of our study was to determine how the intracellular level of TREX1 affects HIV-1 activation and avoidance of innate immunity. Using stable over-expression and CRISPR-mediated gene disruption, we engineered a range of TREX1 levels in human THP-1 monocytes...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29765256/grazoprevir-elbasvir-for-the-treatment-of-adults-with-chronic-hepatitis-c-a-short-review-on-the-clinical-evidence-and-place-in-therapy
#5
REVIEW
Nimisha Sulejmani, Syed-Mohammed Jafri
Chronic hepatitis C virus (HCV) infection impacts approximately 71 million people and approximately 400,000 deaths are attributed to HCV-related liver disease annually worldwide. Mainstay of treatment for over 25 years has been pegylated interferon until the advent of protease inhibitors, which has led to all-oral HCV treatment regimens that have changed the outlook of hepatitis C treatment. Grazoprevir/elbasvir provides high rates of efficacy and tolerability and is an all-oral once daily treatment option for HCV infection...
2018: Hepatic Medicine: Evidence and Research
https://www.readbyqxmd.com/read/29764952/samhd1-phosphorylation-coordinates-the-anti-hiv-1-response-by-diverse-interferons-and-tyrosine-kinase-inhibition
#6
Matthew A Szaniawski, Adam M Spivak, James E Cox, Jonathan L Catrow, Timothy Hanley, Elizabeth S C P Williams, Michel J Tremblay, Alberto Bosque, Vicente Planelles
Macrophages are susceptible to human immunodeficiency virus type 1 (HIV-1) infection despite abundant expression of antiviral proteins. Perhaps the most important antiviral protein is the restriction factor sterile alpha motif domain and histidine/aspartic acid domain-containing protein 1 (SAMHD1). We investigated the role of SAMHD1 and its phospho-dependent regulation in the context of HIV-1 infection in primary human monocyte-derived macrophages and the ability of various interferons (IFNs) and pharmacologic agents to modulate SAMHD1...
May 15, 2018: MBio
https://www.readbyqxmd.com/read/29762170/a-compartmentalized-type-i-interferon-response-in-the-gut-during-chronic-hiv-1-infection-is-associated-with-immunopathogenesis
#7
Stephanie M Dillon, Kejun Guo, Gregory L Austin, Sara Gianella, Phillip A Engen, Ece A Mutlu, John Losurdo, Garth Swanson, Prachi Chakradeo, Ali Keshavarzian, Alan L Landay, Mario Santiago, Cara Wilson
OBJECTIVE(S): Type I IFN (IFN-I) responses confer both protective and pathogenic effects in persistent virus infections. IFN-I diversity, stage of infection and tissue compartment may account for this dichotomy. The gut is a major site of early HIV-1 replication and microbial translocation, but the nature of the IFN-I response in this compartment remains unclear. DESIGN: Samples were obtained from two IRB-approved cross-sectional studies. The first study included individuals with chronic, untreated HIV-1 infection (n = 24) and age/gender balanced uninfected controls (n = 14)...
May 11, 2018: AIDS
https://www.readbyqxmd.com/read/29760693/treatment-intensification-in-hiv-infected-patients-is-associated-with-reduced-frequencies-of-regulatory-t-cells
#8
Eva M Grützner, Tanja Hoffmann, Eva Wolf, Elke Gersbacher, Ashley Neizert, Renate Stirner, Ramona Pauli, Albrecht Ulmer, Jürgen Brust, Johannes R Bogner, Hans Jaeger, Rika Draenert
In untreated HIV infection, the efficacy of T cell responses decreases over the disease course, resulting in disease progression. The reasons for this development are not completely understood. However, immunosuppressive cells are supposedly crucially involved. Treatment strategies to avoid the induction of these cells preserve immune functions and are therefore the object of intense research efforts. In this study, we assessed the effect of treatment intensification [=5-drug antiretroviral therapy (ART)] on the development of suppressive cell subsets...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29758486/poly-i-c-and-lps-induce-distinct-immune-responses-by-ovarian-stromal-fibroblasts
#9
Mickey V Patel, Zheng Shen, Charles R Wira
Despite its anatomical location, the ovary is a site of pathogen exposure in the human female reproductive tract (FRT). However, the role of ovarian stromal fibroblasts in immune protection is unclear. We generated a population of ovarian stromal fibroblasts derived from normal human ovaries that expressed the pattern recognition receptors TLR3, TLR4, RIG-I, & MDA5. Poly (I:C) and LPS, respective mimics of viral and bacterial infections, selectively upregulated antiviral gene expression and secretion of chemokines and antimicrobials...
May 9, 2018: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29755758/autoantibodies-in-chronic-hepatitis-c-virus-infection-impact-on-clinical-outcomes-and-extrahepatic-manifestations
#10
Andrew J Gilman, An K Le, Changqing Zhao, Joseph Hoang, Lee A Yasukawa, Susan C Weber, John M Vierling, Mindie H Nguyen
Goals: To examine the role that autoantibodies (auto-abs) play in chronic hepatitis C virus (HCV) regarding demographics, presence of extrahepatic manifestations and long-term outcomes in a large US cohort. Background: Auto-abs have been reported to be prevalent in patients with chronic HCV infection, but data on the natural history of these patients are limited. Study: The study included 1556 consecutive patients with HCV without concurrent HIV and/or HBV who had testing for antinuclear antibody (ANA), antimitochondrial antibody (AMA), antismooth muscle antibody (ASMA) and/or antiliver kidney microsomal antibody (LKM)...
2018: BMJ Open Gastroenterology
https://www.readbyqxmd.com/read/29743377/equine-myxovirus-resistance-protein-2-restricts-lentiviral-replication-by-blocking-nuclear-uptake-of-capsid-protein
#11
Shuang Ji, Lei Na, Huiling Ren, Yujie Wang, Xiaojun Wang
Human Myxovirus resistance 2 (huMxB) has been shown to be a determinant type I interferon-induced host factor involved in the inhibition of HIV-1 as well as many other primate lentiviruses. This blocking occurs after the reverse transcription of viral RNA and ahead of the integration into the host DNA, which is closely connected to the ability of the protein to bind the viral capsid. To date, Mx2s derived from non-primate animals have shown no capacity for HIV-1 suppression. In this study, we examined the restrictive effect of equine Mx2 (eqMx2) on both the equine infectious anemia virus (EIAV) and HIV-1 and investigated possible mechanisms for its specific function...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29740045/exosome-markers-associated-with-immune-activation-and-oxidative-stress-in-hiv-patients-on-antiretroviral-therapy
#12
Sukrutha Chettimada, David R Lorenz, Vikas Misra, Simon T Dillon, R Keith Reeves, Cordelia Manickam, Susan Morgello, Gregory D Kirk, Shruti H Mehta, Dana Gabuzda
Exosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we characterize plasma exosomes in HIV patients and their relationship to immunological and oxidative stress markers. Plasma exosome fractions were isolated from HIV-positive subjects on ART with suppressed viral load and HIV-negative controls. Exosomes were characterized by electron microscopy, nanoparticle tracking, immunoblotting, and LC-MS/MS proteomics...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29731933/latent-tuberculosis-infection-diagnosis-and-treatment
#13
Biljana Ilievska-Poposka, Marija Metodieva, Maja Zakoska, Cveta Vragoterova, Dejan Trajkov
INTRODUCTION: Latent tuberculosis infection (LTBI) is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of clinically manifested active tuberculosis (TB). Diagnosis and treatment for LTBI are important for TB, especially in high-risk populations. Tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) are used to diagnose LTBI. AIM: The study aims to present the first results with IGRA test compared with TST in the screening of LTBI and the treatment results in the cases with LTBI in Macedonia...
April 15, 2018: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29725337/humanized-mice-engrafted-with-human-hsc-only-or-hsc-and-thymus-support-comparable-hiv-1-replication-immunopathology-and-responses-to-art-and-immune-therapy
#14
Liang Cheng, Jianping Ma, Guangming Li, Lishan Su
Immunodeficient mice reconstituted with human immune tissues and cells (humanized mice) are relevant and robust models for the study of HIV-1 infection, immunopathogenesis, and therapy. In this study, we performed a comprehensive comparison of human immune reconstitution and HIV-1 infection, immunopathogenesis and therapy between immunodeficient NOD/Rag2-/- /γc -/- (NRG) mice transplanted with human HSCs (NRG-hu HSC) and mice transplanted with HSCs and thymus fragments (NRG-hu Thy/HSC) from the same donors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29720521/short-term-pifn-%C3%AE-2a-treatment-does-not-significantly-reduce-the-viral-reservoir-of-siv-infected-art-treated-rhesus-macaques
#15
David Palesch, Steven E Bosinger, Maud Mavigner, James M Billingsley, Cameron Mattingly, Diane Carnathan, Mirko Paiardini, Ann Chahroudi, Thomas Vanderford, Guido Silvestri
The major obstacle to HIV-1 eradication is a reservoir of latently infected cells that persists despite long-term antiretroviral therapy (ART) and causes rapid viral rebound if treatment is interrupted. Type I interferons are immunomodulatory cytokines that induce antiviral factors and have been evaluated for the treatment of HIV-infected individuals, resulting in moderate reduction of viremia and inconclusive data about their effect on reservoir size. Here, we assessed the potential of pegylated IFN-α2a (pIFN-α2a) to reduce the viral reservoir in SIV-infected, ART-treated rhesus macaques (RMs)...
May 2, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29710792/epigenetic-modulation-of-cd8%C3%A2-%C2%BA-t-cell-function-in-lentivirus-infections-a-review
#16
REVIEW
Mukta Nag, Kristina De Paris, Jonathan E Fogle
CD8⁺ T cells are critical for controlling viremia during human immunodeficiency virus (HIV) infection. These cells produce cytolytic factors and antiviral cytokines that eliminate virally- infected cells. During the chronic phase of HIV infection, CD8⁺ T cells progressively lose their proliferative capacity and antiviral functions. These dysfunctional cells are unable to clear the productively infected and reactivated cells, representing a roadblock in HIV cure. Therefore, mechanisms to understand CD8⁺ T cell dysfunction and strategies to boost CD8⁺ T cell function need to be investigated...
April 28, 2018: Viruses
https://www.readbyqxmd.com/read/29706959/cathelicidin-derived-antimicrobial-peptides-inhibit-zika-virus-through-direct-inactivation-and-interferon-pathway
#17
Miao He, Hainan Zhang, Yuju Li, Guangshun Wang, Beisha Tang, Jeffrey Zhao, Yunlong Huang, Jialin Zheng
Zika virus (ZIKV) is a neurotrophic flavivirus that is able to infect pregnant women and cause fetal brain abnormalities. Although there is a significant effort in identifying anti-ZIKV strategies, currently no vaccines or specific therapies are available to treat ZIKV infection. Antimicrobial peptides, which are potent host defense molecules in nearly all forms of life, have been found to be effective against several types of viruses such as HIV-1 and influenza A. However, they have not been tested in ZIKV infection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29688840/active-and-persistent-cytomegalovirus-infections-affect-t-cells-in-young-adult-hiv-patients-commencing-antiretroviral-therapy
#18
Ibnu A Ariyanto, Riwanti Estiasari, Shelley Waters, Endah A T Wulandari, Sonia Fernandez, Silvia Lee, Patricia Price
Altered T cell profiles have been linked with metrics of persistent cytomegalovirus (CMV) infections in healthy aging and older HIV patients stable on antiretroviral therapy (ART). In this study, we use CMV DNA to identify active infections, and levels of CMV-reactive antibody to assess the persistent burden of CMV in a longitudinal study of 78 young adult patients beginning ART in Jakarta, Indonesia, with <200 CD4 T cells/μL. CMV antibodies, inflammatory markers (C-reactive protein [CRP], soluble interferon-α/β receptor) and T cell phenotypes were assessed before ART (V0) and after 1, 3, 6, and 12 months (V1-V12)...
April 24, 2018: Viral Immunology
https://www.readbyqxmd.com/read/29683852/reversing-interferon-alpha-neurotoxicity-in-a-hiv-associated-neurocognitive-disorders-mouse-model
#19
Rajeth Koneru, Heather Bimonte-Nelson, Vincent Ciavatta, Woldeab Haile, Kate Elmore, Jennifer Ward, Leonard Maroun, William R Tyor
OBJECTIVE: Increased brain interferon-alpha (IFNα) is associated with neurodegenerative disorders, including HIV-associated neurocognitive disorders (HAND). HAND occurs in approximately 50% of individuals with HIV despite combined antiretroviral therapy (cART). Therefore, adjunctive therapies must be developed that prevent progression of mild forms of HAND to HIV-associated dementia. Increased IFNα in the CNS has been associated with HAND in patients and in a HAND mouse model. DESIGN AND METHODS: B18R binds IFNα and ameliorates HAND mouse brain histopathology (HIV encephalitis)...
April 19, 2018: AIDS
https://www.readbyqxmd.com/read/29682788/dot-enzyme-linked-immunosorbent-assay-strip-as-a-screening-tool-for-detection-of-autoantibody-to-interferon-gamma-in-sera-of-suspected-cases-of-adult-onset-immunodeficiency
#20
Kritsadee Rattanathammethee, Kriangkrai Chawansuntati, Romanee Chaiwarith, Jutarat Praparattanapan, Khuanchai Supparatpinyo, Jiraprapa Wipasa
BACKGROUND: Being able to detect the presence of autoantibodies to interferon (IFN)-γ in serum is essential for evaluating patients with suspected adult-onset immunodeficiency (AOID) with unusual intracellular infections. Most reported patients with AOID have been Asian, although the exact prevalence of this illness is unknown. To date, no standard assay exists to detect autoantibodies to IFN-γ. An easy-to-use, low-cost assay that can be performed in any laboratory would be a valuable tool for clinical management of AOID, as well as better reveal its prevalence...
April 22, 2018: Journal of Clinical Laboratory Analysis
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