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https://www.readbyqxmd.com/read/29346759/nf-%C3%AE%C2%BAb-chromatin-interactions-drive-diverse-phenotypes-by-modulating-transcriptional-noise
#1
Victor C Wong, Victor L Bass, M Elise Bullock, Arvind K Chavali, Robin E C Lee, Walther Mothes, Suzanne Gaudet, Kathryn Miller-Jensen
Noisy gene expression generates diverse phenotypes, but little is known about mechanisms that modulate noise. Combining experiments and modeling, we studied how tumor necrosis factor (TNF) initiates noisy expression of latent HIV via the transcription factor nuclear factor κB (NF-κB) and how the HIV genomic integration site modulates noise to generate divergent (low-versus-high) phenotypes of viral activation. We show that TNF-induced transcriptional noise varies more than mean transcript number and that amplification of this noise explains low-versus-high viral activation...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346733/synthesis-and-structure-activity-relationship-sar-studies-of-novel-pyrazolopyridine-derivatives-as-inhibitors-of-enterovirus-replication
#2
Yanpeng Xing, Jun Zuo, Paul Krogstad, Michael E Jung
A series of novel pyrazolopyridine compounds have been designed and prepared by a general synthetic route. Their activities against the replication of poliovirus-1, EV-A71, and CV-B3 enteroviruses were evaluated. The comprehensive understanding of the Structure-Activity Relationship was obtained by utilizing the variation of four positions, namely N1, C6, C4 and linker unit. From the screened analogues, the inhibitors with the highest selectivity indices at 50% inhibition of viral replication (SI50) were those with isopropyl at the N1 position and thiophenyl-2-yl unit at C6 position...
January 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29346611/combined-roles-of-atp-and-small-hairpin-rna-in-the-activation-of-rig-i-revealed-by-solution-based-analysis
#3
Neelam Shah, Simone A Beckham, Jacqueline A Wilce, Matthew C J Wilce
RIG-I (retinoic acid inducible gene-I) is a cytosolic innate immune protein that senses viral dsRNA with a 5'-triphosphate overhang. Upon interaction with dsRNA a de-repression of the RIG-I CARD domains takes place that ultimately leads to the production of type I interferons and pro-inflammatory cytokines. Here we investigate the RIG-I conformational rearrangement upon interaction with an activating 5'-triphosphate-10-base pair dsRNA hairpin loop (10bp) compared with a less active 5'-triphosphate-8-base pair dsRNA hairpin loop (8bp)...
January 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29346443/exposure-to-previous-cart-is-associated-with-significant-liver-fibrosis-and-cirrhosis-in-human-immunodeficiency-virus-infected-patients
#4
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/29346435/influenza-a-virus-hemagglutinin-glycosylation-compensates-for-antibody-escape-fitness-costs
#5
Ivan Kosik, William L Ince, Lauren E Gentles, Andrew J Oler, Martina Kosikova, Matthew Angel, Javier G Magadán, Hang Xie, Christopher B Brooke, Jonathan W Yewdell
Rapid antigenic evolution enables the persistence of seasonal influenza A and B viruses in human populations despite widespread herd immunity. Understanding viral mechanisms that enable antigenic evolution is critical for designing durable vaccines and therapeutics. Here, we utilize the primerID method of error-correcting viral population sequencing to reveal an unexpected role for hemagglutinin (HA) glycosylation in compensating for fitness defects resulting from escape from anti-HA neutralizing antibodies...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29346431/sensitivity-and-specificity-of-two-dried-blood-spot-methods-for-hiv-1-viral-load-monitoring-among-patients-in-hanoi-vietnam
#6
Todd M Pollack, Hao T Duong, Phuong T Truong, Thuy T Pham, Cuong D Do, Donn Colby
The use of dried blood spot (DBS) specimens for HIV viral load (VL) monitoring is recommended to support the roll-out of routine VL monitoring in low and middle income countries (LMICs). To better understand the use of DBS for VL monitoring, we evaluated two DBS testing methods, Roche TaqMan® Free Virus Evolution protocol (DBS-FVE) and Roche TaqMan® SPEX protocol (DBS-SPEX)) in patients receiving ART at an HIV clinic in Hanoi, Vietnam. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each DBS testing method at the thresholds of 1000 and 5000 copies/ml compared to plasma VL...
2018: PloS One
https://www.readbyqxmd.com/read/29346424/higher-sequence-diversity-in-the-vaginal-tract-than-in-blood-at-early-hiv-1-infection
#7
Katja Klein, Gabrielle Nickel, Immaculate Nankya, Fred Kyeyune, Korey Demers, Emmanuel Ndashimye, Cynthia Kwok, Pai-Lien Chen, Sandra Rwambuya, Art Poon, Marshall Munjoma, Tsungai Chipato, Josaphat Byamugisha, Peter Mugyenyi, Robert A Salata, Charles S Morrison, Eric J Arts
In the majority of cases, human immunodeficiency virus type 1 (HIV-1) infection is transmitted through sexual intercourse. A single founder virus in the blood of the newly infected donor emerges from a genetic bottleneck, while in rarer instances multiple viruses are responsible for systemic infection. We sought to characterize the sequence diversity at early infection, between two distinct anatomical sites; the female reproductive tract vs. systemic compartment. We recruited 72 women from Uganda and Zimbabwe within seven months of HIV-1 infection...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29346393/computational-study-of-hiv-gp120-as-a-target-for-polyanionic-entry-inhibitors-exploiting-the-v3-loop-region
#8
Louis R Hollingsworth, Anne M Brown, Richard D Gandour, David R Bevan
Multiple approaches are being utilized to develop therapeutics to treat HIV infection. One approach is designed to inhibit entry of HIV into host cells, with a target being the viral envelope glycoprotein, gp120. Polyanionic compounds have been shown to be effective in inhibiting HIV entry, with a mechanism involving electrostatic interactions with the V3 loop of gp120 being proposed. In this study, we applied computational methods to elucidate molecular interactions between the repeat unit of the precisely alternating polyanion, Poly(4,4'-stilbenedicarboxylate-alt-maleic acid) (DCSti-alt-MA) and the V3 loop of gp120 from strains of HIV against which these polyanions were previously tested (IIIb, BaL, 92UG037, JR-CSF) as well as two strains for which gp120 crystal structures are available (YU2, 2B4C)...
2018: PloS One
https://www.readbyqxmd.com/read/29346369/the-rise-of-neglected-tropical-diseases-in-the-new-texas
#9
REVIEW
Peter J Hotez
Within the last five years, the State of Texas has experienced either transmission or outbreaks of Ebola, chikungunya, West Nile, and Zika virus infections. Autochthonous transmission of neglected parasitic and bacterial diseases has also become increasingly reported. The rise of such emerging and neglected tropical diseases (NTDs) has not occurred by accident but instead reflects rapidly evolving changes and shifts in a "new" Texas beset by modern and globalizing forces that include rapid expansions in population together with urbanization and human migrations, altered transportation patterns, climate change, steeply declining vaccination rates, and a new paradigm of poverty known as "blue marble health...
January 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29346349/early-treatment-of-siv-macaques-with-an-%C3%AE-4%C3%AE-7-mab-alters-virus-distribution-and-preserves-cd4-t-cells-in-later-stages-of-infection
#10
P J Santangelo, C Cicala, S N Byrareddy, K T Ortiz, D Little, K E Lindsay, S Gumber, J J Hong, K Jelicic, K A Rogers, C Zurla, F Villinger, A A Ansari, A S Fauci, J Arthos
Integrin α4β7 mediates the trafficking of leukocytes, including CD4+ T cells, to lymphoid tissues in the gut. Virus mediated damage to the gut is implicated in HIV and SIV mediated chronic immune activation and leads to irreversible damage to the immune system. We employed an immuno-PET/CT imaging technique to evaluate the impact of an anti-integrin α4β7 mAb alone or in combination with ART, on the distribution of both SIV infected cells and CD4+ cells in rhesus macaques infected with SIV. We determined that α4β7 mAb reduced viral antigen in an array of tissues of the lung, spleen, axillary, and inguinal lymph nodes...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29346287/development-of-zika-virus-vaccines
#11
REVIEW
Huda Makhluf, Sujan Shresta
Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged as a global threat following the most recent outbreak in Brazil in 2015. ZIKV infection of pregnant women is associated with fetal abnormalities such as microcephaly, and infection of adults can lead to Guillain-Barré syndrome, an autoimmune disease characterized by neurological deficits. Although there are currently licensed vaccines for other flaviviruses, there remains an urgent need for preventative vaccines against ZIKV infection. Herein we describe the current efforts to accelerate the development of ZIKV vaccines using various platforms, including live attenuated virus, inactivated virus, DNA and RNA, viral vectors, and in silico-predicted immunogenic viral epitopes...
January 18, 2018: Vaccines
https://www.readbyqxmd.com/read/29346272/viral-and-antibody-kinetics-and-mosquito-infectivity-of-an-imported-case-of-zika-fever-due-to-asian-genotype-american-strain-in-singapore
#12
Cheong Huat Tan, Li Kiang Tan, Hapuarachchige Chanditha Hapuarachchi, Yee Ling Lai, Pei Sze Jeslyn Wong, Grace Yap, Keng Wai Mak, Wing Yan Wong, Yee Sin Leo, Mei Chun Wong, Lee Ching Ng
We report a case of a Singaporean who acquired Zika virus (ZIKV) during a visit to Cuba. The infection was confirmed using molecular and serological methods. This report highlights potential drawbacks of using IgG serology for diagnosis of flavivirus infections in endemic regions. The low viremia detected during the early phase of this case resulted in low mosquito infectivity rates, suggesting the possibility of ZIKV transmission prior to clinical onset. The report also emphasizes the challenges of public health interventions for Zika fever and the importance of sustaining a low vector population to reduce the risk of arbovirus transmission in vulnerable regions...
January 18, 2018: Viruses
https://www.readbyqxmd.com/read/29346270/resistance-to-hiv-integrase-inhibitors-about-r263k-and-e157q-mutations
#13
REVIEW
Charlotte Charpentier, Diane Descamps
The use of integrase inhibitors (INI) is increasing in antiretroviral therapies (ART) and INI are not all equal regarding genetic barrier to resistance. The aim of this manuscript was to review main in vivo and in vitro knowledge about two particular integrase resistance-associated mutations: R263K and E157Q. The R263K mutation was the first mutation rarely found selected at time of virological failure in patients failing a first-line dolutegravir-based treatment. Further in vitro studies on R263K mutants showed a moderate increase in phenotypic resistance level and a drastic reduction in viral replicative capacity...
January 18, 2018: Viruses
https://www.readbyqxmd.com/read/29346185/higher-art-adherence-is-associated-with-lower-systemic-inflammation-in-treatment-na%C3%A3-ve-ugandans-who-achieve-virologic-suppression
#14
Jose R Castillo-Mancilla, Mary Morrow, Yap Boum, Helen Byakwaga, Jessica E Haberer, Jeffrey N Martin, David Bangsberg, Samantha Mawhinney, Nicholas Musinguzi, Yong Huang, Russell P Tracy, Tricia H Burdo, Kenneth Williams, Conrad Muzoora, Peter W Hunt, Mark J Siedner
BACKGROUND: Residual systemic inflammation persists despite suppressive antiretroviral therapy (ART) and is associated with non-AIDS clinical outcomes. We aimed to evaluate the association between ART adherence and inflammation in Ugandans living with HIV who were predominantly receiving nevirapine-based ART with a thymidine analog backbone and were virologically suppressed by conventional assays. METHODS: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble (s)CD14, sCD163, the kynurenine/tryptophan (K/T) ratio, in addition to CD8 T-cell activation, were measured at baseline and 6 months after ART initiation in treatment-naïve adults who achieved an undetectable plasma HIV RNA (<400 copies/mL) at their 6-month visit...
January 16, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29346085/performance-of-the-bioplex-2200-hiv-ag-ab-assay-for-identifying-acute-hiv-infection
#15
Susan H Eshleman, Estelle Piwowar-Manning, Mariya V Sivay, Barbara Debevec, Stephanie Veater, Laura McKinstry, Linda-Gail Bekker, Sharon Mannheimer, Robert M Grant, Margaret A Chesney, Thomas J Coates, Beryl A Koblin, Jessica M Fogel
BACKGROUND: Assays that detect HIV antigen (Ag) and antibody (Ab) can be used to screen for HIV infection. OBJECTIVES: To compare the performance of the BioPlex 2200 HIV Ag-Ab assay and two other Ag/Ab combination assays for detection of acute HIV infection. STUDY DESIGN: Samples were obtained from 24 individuals (18 from the US, 6 from South Africa); these individuals were classified as having acute infection based on the following criteria: positive qualitative RNA assay; two negative rapid tests; negative discriminatory test...
January 11, 2018: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/29346074/a-partial-deletion-within-foot-and-mouth-disease-virus-non-structural-protein-3a-causes-clinical-attenuation-in-cattle-but-does-not-prevent-subclinical-infection
#16
Carolina Stenfeldt, Jonathan Arzt, Juan M Pacheco, Douglas P Gladue, George R Smoliga, Ediane B Silva, Luis L Rodriguez, Manuel V Borca
Deletions within the 3A coding region of foot-and-mouth disease virus (FMDV) are associated with decreased virulence in cattle; however, the mechanisms are unknown. We compared experimental infection of cattle with virulent FMDV O1Campos (O1Ca) and a mutant derivative (O1Ca∆3A) lacking residues 87-106 of 3A. Unexpectedly, primary infection of the nasopharyngeal mucosa was similar for both viruses. However, while O1Ca caused viremia and fulminant clinical disease, O1Ca∆3A infection was subclinical and aviremic...
January 12, 2018: Virology
https://www.readbyqxmd.com/read/29346073/extensive-conservation-of-prokaryotic-ribosomal-binding-sites-in-known-and-novel-picobirnaviruses
#17
Siddharth R Krishnamurthy, David Wang
Currently, the Leviviridae and Cystoviridae are the only two recognized families of prokaryotic RNA viruses. Picobirnaviruses, which are bisegmented double-stranded RNA viruses commonly found in animal stool samples, are currently thought to be animal viruses, but have not been propagated in cell culture or in an animal model. We hypothesize that picobirnaviruses are prokaryotic RNA viruses. We identified and analyzed the genomes of 38 novel picobirnaviruses and determined that a classical bacterial sequence motif, the ribosomal binding site (RBS), is present in the 5' untranslated regions (5' UTRs) of all of the novel as well as all previously published picobirnavirus sequences...
January 12, 2018: Virology
https://www.readbyqxmd.com/read/29345964/immune-response-to-dengue-and-zika
#18
Annie Elong Ngono, Sujan Shresta
Flaviviruses such as dengue (DENV), yellow fever (YFV), West Nile (WNV), and Zika (ZIKV) are human pathogens of global significance. In particular, DENV causes the most prevalent mosquito-borne viral diseases in humans, and ZIKV emerged from obscurity into the spotlight in 2016 as the etiologic agent of congenital Zika syndrome. Owing to the recent emergence of ZIKV as a global pandemic threat, the roles of the immune system during ZIKV infections are as yet unclear. In contrast, decades of DENV research implicate a dual role for the immune system in protection against and pathogenesis of DENV infection...
January 18, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29345922/efficient-fusion-at-neutral-ph-by-human-immunodeficiency-virus-gp41-trimers-containing-the-fusion-peptide-and-transmembrane-domain
#19
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/29345855/increased-estradiol-in-hepatitis-e-virus-infected-pregnant-women-promote-viral-replication
#20
Chenchen Yang, Wenhai Yu, Yanhong Bi, Feiyan Long, Yunlong Li, Daqiao Wei, Xianhui Hao, Jianwen Situ, Yongqin Zhao, Fen Huang
Hepatitis E virus (HEV) infection causes subclinical diseases, leading to high mortality (> 25%) in pregnant women. HEV replication is aggressively escalated in pregnant women, especially in the third trimester of pregnancy. Estrogen plays an important role in pregnancy. However, the pathogenesis of HEV in pregnant women or immunosuppressive pregnant women (such as HIV-infected, or organ-transplanted pregnant women) remains unclear. We investigated the role of estradiol in HEV infection in a cell culture system...
January 18, 2018: Journal of Viral Hepatitis
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