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https://www.readbyqxmd.com/read/29352292/rna-seq-of-kaposi-s-sarcoma-reveals-alterations-in-glucose-and-lipid-metabolism
#1
For Yue Tso, Andrew V Kossenkov, Salum J Lidenge, Owen Ngalamika, John R Ngowi, Julius Mwaiselage, Jayamanna Wickramasinghe, Eun Hee Kwon, John T West, Paul M Lieberman, Charles Wood
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). It is endemic in a number of sub-Saharan African countries with infection rate of >50%. The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer in the region with poor prognosis and high mortality. Disease markers and cellular functions associated with KS tumorigenesis remain ill-defined. Several studies have attempted to investigate changes of the gene profile with in vitro infection of monoculture models, which are not likely to reflect the cellular complexity of the in vivo lesion environment...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29351445/impact-of-hiv-infection-on-alpha-1-antitrypsin-in-the-lung
#2
Sarah E Stephenson, Carole L Wilson, Kristina Crothers, Engi F Attia, Cherry Wongtrakool, Irina Petrache, Lynn M Schnapp
BACKGROUND: Emphysema is one of the most common lung diseases in HIV+ individuals. The pathogenesis of HIV-associated emphysema remains unclear; however, radiographic distribution and earlier age of presentation of emphysema in the lungs of HIV+ patients are similar to deficiency of alpha-1 antitrypsin (A1AT), a key elastase inhibitor in the lung. Reduced levels of circulating A1AT have been detected in HIV+ patients, suggesting a potential mechanism for emphysema development. In the present study, we asked if A1AT levels and activity in the bronchoalveolar lavage fluid (BALF) differ in patients with and without HIV and emphysema...
December 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29350337/baseline-neurocognitive-functioning-predicts-viral-load-suppression-at-1-year-follow-up-among-newly-diagnosed-hiv-infected-patients
#3
Lokesh Shahani, Lucrecia Salazar, Steven P Woods, Rodrigo Hasbun
The current prospective observational study evaluated the impact of baseline neurocognitive impairment on future viral load suppression among antiretroviral medication naive persons newly diagnosed with HIV infection. We used the Montreal Cognitive Assessment (MoCA) score less than 26, to identify patients with neurocognitive deficits. Of the 138 patients enrolled; virologic suppression was seen in 61% of the participants, while 72% of the participants had a MoCA score less than 26 at baseline. Variables significantly associated with low MoCA score included higher age (p < 0...
January 19, 2018: AIDS and Behavior
https://www.readbyqxmd.com/read/29348664/stress-induced-trbp-phosphorylation-enhances-its-interaction-with-pkr-to-regulate-cellular-survival
#4
Evelyn Chukwurah, Rekha C Patel
Transactivation response element RNA-binding protein (TRBP or TARBP2) initially identified to play an important role in human immunodeficiency virus (HIV) replication also has emerged as a regulator of microRNA biogenesis. In addition, TRBP functions in signaling pathways by negatively regulating the interferon-induced double-stranded RNA (dsRNA)-activated protein kinase (PKR) during viral infections and cell stress. During cellular stress, PKR is activated and phosphorylates the α subunit of the eukaryotic translation factor eIF2, leading to the cessation of general protein synthesis...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29347817/biochemical-basis-of-apobec3-deoxycytidine-deaminase-activity-on-diverse-dna-substrates
#5
Madison B Adolph, Robin P Love, Linda Chelico
The Apolipoprotein B mRNA editing complex (APOBEC) family of enzymes are single-stranded polynucleotide cytidine deaminases. These enzymes catalyze the deamination of cytidine in RNA or single-stranded DNA, which forms uracil. From this eleven member enzyme family in humans, the deamination of single-stranded DNA by the seven APOBEC3 family members are considered here. The APOBEC3 family has many roles such as, restricting endogenous and exogenous retrovirus replication and retrotransposon insertion events and reducing DNA-induced inflammation...
January 18, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29346443/exposure-to-previous-cart-is-associated-with-significant-liver-fibrosis-and-cirrhosis-in-human-immunodeficiency-virus-infected-patients
#6
Evrim Anadol, Kristina Lust, Christoph Boesecke, Carolynne Schwarze-Zander, Raphael Mohr, Jan-Christian Wasmuth, Jürgen Kurt Rockstroh, Jonel Trebicka
INTRODUCTION: Combined antiretroviral therapy (cART) has improved survival in HIV-patients. While the first antiretrovirals, which became available in particular D-drugs (especially didanosine and stavudine) and unboosted protease inhibitors, may impair liver function, the modern cART seems to decrease liver fibrosis. This study assessed the influence of exposure to previous antiretrovirals on liver fibrosis in HIV-infected patients. METHODS: This observational cross-sectional single-center study recruited 333 HIV patients and assessed liver fibrosis using transient elastography (TE)...
2018: PloS One
https://www.readbyqxmd.com/read/29346413/genetic-diversity-and-potential-routes-of-transmission-of-mycobacterium-bovis-in-mozambique
#7
Adelina Machado, Teresa Rito, Solomon Ghebremichael, Nuelma Muhate, Gabriel Maxhuza, Custodia Macuamule, Ivania Moiane, Baltazar Macucule, Angelica Suzana Marranangumbe, Jorge Baptista, Joaquim Manguele, Tuija Koivula, Elizabeth Maria Streicher, Robin Mark Warren, Gunilla Kallenius, Paul van Helden, Margarida Correia-Neves
Bovine tuberculosis is a zoonotic disease with largely unknown impact in Africa, with risk factors such as HIV and direct contact with animals or consumption of Mycobacterium bovis infected animal products. In order to understand and quantify this risk and design intervention strategies, good epidemiological studies are needed. Such studies can include molecular typing of M. bovis isolates. The aim of this study was to apply these tools to provide novel information concerning the distribution of bovine tuberculosis in cattle in Mozambique and thereby provide relevant information to guide policy development and strategies to contain the disease in livestock, and reduce the risk associated with transmission to humans...
January 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29345933/large-scale-functional-group-symmetry-adapted-perturbation-theory-on-graphical-processing-units
#8
Robert M Parrish, Keiran C Thompson, Todd J Martínez
Symmetry-adapted perturbation theory (SAPT) is a valuable method for analyzing intermolecular interactions. The functional group SAPT partition (F-SAPT) has been introduced to provide additional insight into the origins of noncovalent interactions. Until now, SAPT analysis has been too costly for large ligand-protein complexes where it could provide key insights for chemical modifications that might improve ligand binding. In this paper, we present a large-scale implementation of F-SAPT which is especially efficient when one of the interacting monomers is significantly larger than the other, as is usually the case for drug-protein interactions...
January 18, 2018: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29345922/efficient-fusion-at-neutral-ph-by-human-immunodeficiency-virus-gp41-trimers-containing-the-fusion-peptide-and-transmembrane-domain
#9
Shuang Liang, Punsisi Ratnayake, Craig Keinath, Lihui Jia, Robert Wolfe, Ahinsa Ranaweera, David P Weliky
Human immunodeficiency virus (HIV) is membrane-enveloped and an initial infection step is joining/fusion of viral and cell membranes. This step is catalyzed by gp41 which is a single-pass integral viral membrane protein. The protein contains a ~170-residue ectodomain located outside the virus that is important for fusion, and includes the fusion peptide (FP), N-helix, loop, C-helix, and viral membrane-proximal external region (MPER). The virion initially has non-covalent complexes between three gp41 ectodomains and three gp120 proteins...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29345375/understanding-the-regulation-of-apobec3-expression-current-evidence-and-much-to-learn
#10
REVIEW
Daniela Angela Covino, Maria Cristina Gauzzi, Laura Fantuzzi
The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of cytosine deaminases plays crucial roles in innate immunity through the ability of restricting viral replication by deamination and mutation of viral genomes. The antiviral function of these proteins was first discovered when research in the field of HIV infection revealed that one member of the family, namely APOBEC3G, restricts HIV infection in T lymphocytes and that the viral infectivity factor protein drives the proteosomal degradation of this enzyme, thus overriding its antiviral function...
December 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344357/examining-the-effectiveness-of-a-cognitive-intervention-to-improve-cognitive-function-in-a-population-of-older-adults-living-with-hiv-a-pilot-study
#11
Judy A Frain, Ling Chen
Objective: The purpose of this randomized-controlled pilot study was to explore the effectiveness of a home-based computerized cognitive training intervention in improving cognitive function in a population of older adults with mild cognitive impairment who are living with HIV. Methods: In all, 24 participants were enrolled in this study. All study participants were impaired [defined as Montreal Cognitive Assessment (MoCA) score < 26]; 12 were randomly assigned to a computer-training intervention group and 12 to a control group...
January 2018: Therapeutic Advances in Infectious Disease
https://www.readbyqxmd.com/read/29343613/restricted-hiv-1-env-glycan-engagement-by-lectin-reengineered-davei-protein-chimera-is-sufficient-for-lytic-inactivation-of-the-virus
#12
Bibek Parajuli, Kriti Acharya, Harry C Bach, Bijay Parajuli, Shiyu Zhang, Amos B Smith, Cameron F Abrams, Irwin Chaiken
We previously reported first generation recombinant DAVEI construct, a dual action virus entry inhibitor composed of cyanovirin-N (CVN) fused to a membrane proximal external region (MPER) or its derivative peptide Trp3. DAVEI exhibits potent and irreversible inactivation of HIV-1 viruses by dual engagement of gp120 and gp41. However, the promiscuity of CVN to associate with multiple glycosylation sites in gp120 and its multivalency limit current understanding of the molecular arrangement of the DAVEI molecules on trimeric spike...
January 17, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29343578/a-new-quinoline-brd4-inhibitor-targets-a-distinct-latent-hiv-1-reservoir-for-re-activation-from-other-shock-drugs
#13
Erik Abner, Mateusz Stoszko, Lei Zeng, Heng-Chang Chen, Andrea Izquierdo-Bouldstridge, Tsuyoshi Konuma, Eduard Zorita, Elisa Fanunza, Qiang Zhang, Tokameh Mahmoudi, Ming-Ming Zhou, Guillaume J Filion, Albert Jordan
Upon HIV-1 infection, a reservoir of latently infected resting T cells prevents the eradication of the virus from patients. To achieve complete depletion, the existing virus-suppressing antiretroviral therapy must be combined with drugs that reactivate the dormant viruses. We previously described a novel chemical scaffold compound, MMQO (8-methoxy-6-methylquinolin-4-ol) that is able to reactivate viral transcription in several models of HIV latency including J-Lat cells through an unknown mechanism. MMQO potentiates the activity of known latency-reversing agents (LRAs) or 'shock' drugs such as PKC agonists or HDAC inhibitors...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343083/polarized-macrophage-subsets-differentially-express-the-drug-efflux-transporters-mrp1-and-bcrp-resulting-in-altered-hiv-production
#14
Hui He, Merrion Buckley, Bernard Britton, Ying Mu, Kristin Warner, Santosh Kumar, Theodore J Cory
Introduction Macrophages play an important role in HIV, where they are a cellular reservoir. Macrophages are polarized into two phenotypes: pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages, which may have altered expression of drug efflux transporters, including BCRP and MRP1. These differences may result in subtherapeutic concentrations of antiretrovirals inside of macrophages and viral replication. Methods U937 and U1 cells were polarized to the M1 or M2 phenotype via IFN-γ and LPS, or IL-4, IL-13, and LPS...
January 2018: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/29343078/quality-of-life-among-hiv-infected-individuals-failing-first-line-antiretroviral-therapy-in-resource-limited-settings
#15
Thiago S Torres, Linda J Harrison, Alberto M La Rosa, Jeffrey A Lavenberg, Lu Zheng, Steven A Safren, McNeil Ngongondo, Selvamuthu Poongulali, Mitch Matoga, Wadzanai Samaneka, Ann C Collier, Michael D Hughes
We evaluated health-related quality of life (QoL) in HIV infection participants with virologic failure (VF) on first-line antiretroviral therapy (ART) in 9 resource-limited settings (RLS). ACTG SF-21 was completed by 512 participants at A5273 study entry; 8 domains assessed: general health perceptions (GHP), physical functioning (PF), role functioning (RF), social functioning (SF), cognitive functioning (CF), pain (P), mental health (MH), and energy/fatigue (E/F); each was scored between 0 (worst) to 100 (best)...
January 18, 2018: AIDS Care
https://www.readbyqxmd.com/read/29339432/deregulation-of-hdac5-by-viral-interferon-regulatory-factor-3-plays-an-essential-role-in-kaposi-s-sarcoma-associated-herpesvirus-induced-lymphangiogenesis
#16
Hye-Ra Lee, Fan Li, Un Yung Choi, Hye Ryun Yu, Grace M Aldrovandi, Pinghui Feng, Shou-Jiang Gao, Young-Kwon Hong, Jae U Jung
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS), which is one of the most common HIV-associated neoplasms. The endothelium is the thin layer of squamous cells where vascular blood endothelial cells (BECs) line the interior surface of blood vessels and lymphatic endothelial cells (LECs) are in direct contact with lymphatic vessels. The KS lesions contain a prominent compartment of neoplastic spindle morphology cells that are closely related to LECs. Furthermore, while KSHV can infect both LECs and BECs in vitro, its infection activates genetic programming related to lymphatic endothelial cell fate, suggesting that lymphangiogenic pathways are involved in KSHV infection and malignancy...
January 16, 2018: MBio
https://www.readbyqxmd.com/read/29337702/changing-concepts-of-hiv-infection-and-renal-disease
#17
Jean Hou, Cynthia C Nast
PURPOSE OF REVIEW: Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) was identified as the major renal manifestation of HIV infection early in the HIV epidemic. However, HIV infection now is associated with a different spectrum of renal lesions leading to chronic kidney disease. This review examines the changes in kidney injury occurring in the current HIV era and the factors involved in this transformation of disease expression. RECENT FINDINGS: The incidence of HIVAN and opportunistic infections in HIV-infected individuals has declined in concert with the use of effective combination antiretroviral agents...
January 13, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29336469/transcriptional-regulation-of-hiv-1-host-factor-commd1-by-the-sp-family
#18
Eriko Kudo, Manabu Taura, Mary Ann Suico, Hiroki Goto, Hirofumi Kai, Seiji Okada
Copper metabolism Murr1 domain containing 1 (COMMD1) has multiple functions in the regulation of protein stability at the plasma membrane and in the cytoplasm. However, the regulation of COMMD1 transcriptional has remained to be elucidated. In the present study, the 5'‑flanking region (‑1,192/+83 bp) of the human COMMD1 gene was cloned. It was observed that the COMMD1 promoter region contains GC‑rich region that has 7 putative Sp1‑binding sites via in silico analysis. The proximal promoter region at ‑289/+83 bp was required for COMMD1 basal promoter activity by deletion constructs of COMMD1 promoter...
January 15, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29334883/renal-outcomes-in-patients-initiated-on-tenofovir-disoproxil-fumarate-based-antiretroviral-therapy-at-a-community-health-centre-in-malawi
#19
Bongani Chikwapulo, Bagrey Ngwira, Jean Baptiste Sagno, Rhys Evans
Tenofovir-based antiretroviral therapy (TDF ART) is the first-line regimen for human immunodeficiency virus (HIV) in Africa. However, contemporary data on nephrotoxicity are lacking. We determined the renal outcomes of patients commenced on TDF ART in Malawi. ART-naïve patients initiated on TDF ART at a community health centre between 1 July 2013 and 31 December 2015 were included. The estimated glomerular filtration rate (eGFR, Cockcroft-Gault) was recorded at the initiation of therapy and over 18 months thereafter...
January 1, 2018: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/29334553/post-treatment-controllers-after-treatment-interruption-in-chronically-hiv-infected-patients
#20
Franco Maggiolo, Elisa Di Filippo, Laura Comi, Annapaola Callegaro
OBJECTIVE: Control HIV replication requires continuous combined antiretroviral therapy (cART) as discontinuation of cART results in a rapid viral rebound. However, a few individuals exist who took cART for several years and did not show the expected viral rebound after treatment cessation. Most post-treatment controllers (PTCs) are early treated individuals. We report three cases who started cART during chronic infection. DESIGN: Patients were treated and monitored according to Italian guidelines...
January 13, 2018: AIDS
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