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Retrovirology

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https://www.readbyqxmd.com/read/29329553/inhibitors-of-the-integrase-transportin-sr2-interaction-block-hiv-nuclear-import
#1
Jonas Demeulemeester, Jolien Blokken, Stéphanie De Houwer, Lieve Dirix, Hugo Klaassen, Arnaud Marchand, Patrick Chaltin, Frauke Christ, Zeger Debyser
BACKGROUND: Combination antiretroviral therapy efficiently suppresses HIV replication in infected patients, transforming HIV/AIDS into a chronic disease. Viral resistance does develop however, especially under suboptimal treatment conditions such as poor adherence. As a consequence, continued exploration of novel targets is paramount to identify novel antivirals that do not suffer from cross-resistance with existing drugs. One new promising class of targets are HIV protein-cofactor interactions...
January 12, 2018: Retrovirology
https://www.readbyqxmd.com/read/29329537/the-hiv-1-accessory-proteins-nef-and-vpu-downregulate-total-and-cell-surface-cd28-in-cd4-t-cells
#2
Emily N Pawlak, Brennan S Dirk, Rajesh Abraham Jacob, Aaron L Johnson, Jimmy D Dikeakos
BACKGROUND: The HIV-1 accessory proteins Nef and Vpu alter cell surface levels of multiple host proteins to modify the immune response and increase viral persistence. Nef and Vpu can downregulate cell surface levels of the co-stimulatory molecule CD28, however the mechanism of this function has not been completely elucidated. RESULTS: Here, we provide evidence that Nef and Vpu decrease cell surface and total cellular levels of CD28. Moreover, using inhibitors we implicate the cellular degradation machinery in the downregulation of CD28...
January 12, 2018: Retrovirology
https://www.readbyqxmd.com/read/29316956/next-generation-in-situ-hybridization-approaches-to-define-and-quantify-hiv-and-siv-reservoirs-in-tissue-microenvironments
#3
REVIEW
Claire Deleage, Chi N Chan, Kathleen Busman-Sahay, Jacob D Estes
The development of increasingly safe and effective antiretroviral treatments for human immunodeficiency virus (HIV) over the past several decades has led to vastly improved patient survival when treatment is available and affordable, an outcome that relies on uninterrupted adherence to combination antiretroviral therapy for life. Looking to the future, the discovery of an elusive 'cure' for HIV will necessitate highly sensitive methods for detecting, understanding, and eliminating viral reservoirs. Next-generation, in situ hybridization (ISH) approaches offer unique and complementary insights into viral reservoirs within their native tissue environments with a high degree of specificity and sensitivity...
January 9, 2018: Retrovirology
https://www.readbyqxmd.com/read/29316955/single-molecule-techniques-to-quantify-and-genetically-characterise-persistent-hiv
#4
REVIEW
Xiao Qian Wang, Sarah Palmer
Antiretroviral therapy effectively suppresses, but does not eradicate HIV-1 infection. Persistent low-level HIV-1 can still be detected in plasma and cellular reservoirs even after years of effective therapy, and cessation of current treatments invariably results in resumption of viral replication. Efforts to eradicate persistent HIV-1 require a comprehensive examination of the quantity and genetic composition of HIV-1 within the plasma and infected cells located in the peripheral blood and tissues throughout the body...
January 9, 2018: Retrovirology
https://www.readbyqxmd.com/read/29310678/computational-analysis-of-envelope-glycoproteins-from-diverse-geographical-isolates-of-bovine-leukemia-virus-identifies-highly-conserved-peptide-motifs
#5
Aneta Pluta, Lorraine M Albritton, Marzena Rola-Łuszczak, Jacek Kuźmak
BACKGROUND: Bovine leukemia virus (BLV) is a deltaretrovirus infecting bovine B cells and causing enzootic bovine leucosis. The SU or surface subunit, gp51, of its envelope glycoprotein is involved in receptor recognition and virion attachment. It contains the major neutralizing and CD4+ and CD8+ T cell epitopes found in naturally infected animals. In this study, we aimed to determine global variation and conservation within gp51 in the context of developing an effective global BLV vaccine...
January 8, 2018: Retrovirology
https://www.readbyqxmd.com/read/29304821/impact-of-the-hiv-1-genetic-background-and-hiv-1-population-size-on-the-evolution-of-raltegravir-resistance
#6
Axel Fun, Thomas Leitner, Linos Vandekerckhove, Martin Däumer, Alexander Thielen, Bernd Buchholz, Andy I M Hoepelman, Elizabeth H Gisolf, Pauline J Schipper, Annemarie M J Wensing, Monique Nijhuis
BACKGROUND: Emergence of resistance against integrase inhibitor raltegravir in human immunodeficiency virus type 1 (HIV-1) patients is generally associated with selection of one of three signature mutations: Y143C/R, Q148K/H/R or N155H, representing three distinct resistance pathways. The mechanisms that drive selection of a specific pathway are still poorly understood. We investigated the impact of the HIV-1 genetic background and population dynamics on the emergence of raltegravir resistance...
January 5, 2018: Retrovirology
https://www.readbyqxmd.com/read/29268769/systems-serology-profiling-vaccine-induced-humoral-immunity-against-hiv
#7
REVIEW
Amy W Chung, Galit Alter
The results of the RV144 HIV vaccine, in combination with several recent non-human primate vaccine studies continue to highlight the potentially protective role of non-neutralizing Fc functional antibodies in HIV vaccine design. For many currently licensed vaccines, assays that detect antigen-specific antibody titers or neutralization levels have been used as a correlate of protection. However, antibodies can confer protection through multiple other mechanisms beyond neutralization, or mechanisms which are not dependent on total antibody titers...
December 21, 2017: Retrovirology
https://www.readbyqxmd.com/read/29268753/innovations-in-the-quantitative-virus-outgrowth-assay-and-its-use-in-clinical-trials
#8
REVIEW
Nicholas J Norton, Axel Fun, Mikaila Bandara, Mark R Wills, Hoi Ping Mok, Andrew M L Lever
A robust measure of the size of the latent HIV reservoir is essential to quantifying the effect of interventions designed to deplete the pool of reactivatable, replication competent proviruses. In addition to the ability to measure a biologically relevant parameter, any assay designed to be used in a clinical trial needs to be reproducible and scalable. The need to quantify the number of resting CD4+ T cells capable of releasing infectious virus has led to the development of the quantitative viral outgrowth assay (VOA)...
December 21, 2017: Retrovirology
https://www.readbyqxmd.com/read/29258557/moloney-leukemia-virus-10-mov10-inhibits-the-degradation-of-apobec3g-through-interference-with-the-vif-mediated-ubiquitin-proteasome-pathway
#9
Cancan Chen, Xiaocao Ma, Qifei Hu, Xinghua Li, Feng Huang, Junsong Zhang, Ting Pan, Jinyu Xia, Chao Liu, Hui Zhang
BACKGROUND: MOV10 protein has ATP-dependent 5'-3' RNA helicase activity and belongs to the UPF1p superfamily. It can inhibit human immunodeficiency virus type 1 (HIV-1) replication at multiple stages and interact with apolipoprotein-B-mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G), a member of the cytidine deaminase family that exerts potent inhibitory effects against HIV-1 infection. However, HIV-1-encoded virion infectivity factor (Vif) protein specifically mediates the degradation of A3G via the ubiquitin-proteasome system (UPS)...
December 19, 2017: Retrovirology
https://www.readbyqxmd.com/read/29197389/foamy-virus-zoonotic-infections
#10
Delia M Pinto-Santini, Carolyn R Stenbak, Maxine L Linial
BACKGROUND: Foamy viruses (FV) are ancient complex retroviruses that differ from orthoretroviruses such as human immunodeficiency virus (HIV) and murine leukemia virus (MLV) and comprise a distinct subfamily of retroviruses, the Spumaretrovirinae. FV are ubiquitous in their natural hosts, which include cows, cats, and nonhuman primates (NHP). FV are transmitted mainly through saliva and appear nonpathogenic by themselves, but they may increase morbidity of other pathogens in coinfections...
December 2, 2017: Retrovirology
https://www.readbyqxmd.com/read/29179726/modulation-of-the-functional-association-between-the-hiv-1-intasome-and-the-nucleosome-by-histone-amino-terminal-tails
#11
Mohamed S Benleulmi, Julien Matysiak, Xavier Robert, Csaba Miskey, Eric Mauro, Delphine Lapaillerie, Paul Lesbats, Stéphane Chaignepain, Daniel R Henriquez, Christina Calmels, Oyindamola Oladosu, Eloïse Thierry, Oscar Leon, Marc Lavigne, Marie-Line Andreola, Olivier Delelis, Zoltán Ivics, Marc Ruff, Patrice Gouet, Vincent Parissi
BACKGROUND: Stable insertion of the retroviral DNA genome into host chromatin requires the functional association between the intasome (integrase·viral DNA complex) and the nucleosome. The data from the literature suggest that direct protein-protein contacts between integrase and histones may be involved in anchoring the intasome to the nucleosome. Since histone tails are candidates for interactions with the incoming intasomes we have investigated whether they could participate in modulating the nucleosomal integration process...
November 28, 2017: Retrovirology
https://www.readbyqxmd.com/read/29162141/more-than-meets-the-i-the-diverse-antiviral-and-cellular-functions-of-interferon-induced-transmembrane-proteins
#12
REVIEW
Guoli Shi, Olivier Schwartz, Alex A Compton
The first responders of human antiviral immunity are components of the intrinsic immune response that reside within each and every one of our cells. This cell-autonomous arsenal consists of nucleic acid sensors and antiviral effectors strategically placed by evolution to detect and restrict invading viruses. While some factors are present at baseline to allow for constant surveillance of the cell interior, others are upregulated by cytokines (such as interferons) that signal a viral infection underway in neighboring cells...
November 21, 2017: Retrovirology
https://www.readbyqxmd.com/read/29157283/the-mouse-viral-outgrowth-assay-avatars-for-the-detection-of-hiv-1-reservoirs
#13
REVIEW
Kelly A Metcalf Pate, Joel N Blankson
Sensitive assays are needed for the detection of residual viral reservoirs in HIV-1-infected subjects on suppressive combination antiretroviral therapy regimens to determine whether eradication strategies are effective. Mouse viral outgrowth assays have recently been developed and have the potential to be more sensitive than traditional in vitro quantitative viral outgrowth assays. In this article we describe these assays and review several studies that have used them to measure the latent reservoir.
November 21, 2017: Retrovirology
https://www.readbyqxmd.com/read/29141633/genome-modification-of-cxcr4-by-staphylococcus-aureus-cas9-renders-cells-resistance-to-hiv-1-infection
#14
Qiankun Wang, Shuliang Chen, Qiaoqiao Xiao, Zhepeng Liu, Shuai Liu, Panpan Hou, Li Zhou, Wei Hou, Wenzhe Ho, Chunmei Li, Li Wu, Deyin Guo
BACKGROUND: The CRISPR/Cas9 system has been widely used for genome editing in mammalian cells. CXCR4 is a co-receptor for human immunodeficiency virus type 1 (HIV-1) entry, and loss of CXCR4 function can protect cells from CXCR4 (X4)-tropic HIV-1 infection, making CXCR4 an important target for HIV-1 gene therapy. However, the large size of the CRISPR/SpCas9 system presents an obstacle to its efficient delivery into primary CD4(+) T cells. Recently, a small Staphylococcus aureus Cas9 (SaCas9) has been developed as a genome editing tool can address this question...
November 15, 2017: Retrovirology
https://www.readbyqxmd.com/read/29121951/increasing-the-cpg-dinucleotide-abundance-in-the-hiv-1-genomic-rna-inhibits-viral-replication
#15
Irati Antzin-Anduetza, Charlotte Mahiet, Luke A Granger, Charlotte Odendall, Chad M Swanson
BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) structural protein Gag is necessary and sufficient to form viral particles. In addition to encoding the amino acid sequence for Gag, the underlying RNA sequence could encode cis-acting elements or nucleotide biases that are necessary for viral replication. Furthermore, RNA sequences that inhibit viral replication could be suppressed in gag. However, the functional relevance of RNA elements and nucleotide biases that promote or repress HIV-1 replication remain poorly understood...
November 9, 2017: Retrovirology
https://www.readbyqxmd.com/read/29121950/the-hiv-1-integrase-ledgf-allosteric-inhibitor-mut-a-resistance-profile-impairment-of-virus-maturation-and-infectivity-but-without-influence-on-rna-packaging-or-virus-immunoreactivity
#16
Céline Amadori, Yme Ubeles van der Velden, Damien Bonnard, Igor Orlov, Nikki van Bel, Erwann Le Rouzic, Laia Miralles, Julie Brias, Francis Chevreuil, Daniele Spehner, Sophie Chasset, Benoit Ledoussal, Luzia Mayr, François Moreau, Felipe García, José Gatell, Alessia Zamborlini, Stéphane Emiliani, Marc Ruff, Bruno P Klaholz, Christiane Moog, Ben Berkhout, Montserrat Plana, Richard Benarous
BACKGROUND: HIV-1 Integrase (IN) interacts with the cellular co-factor LEDGF/p75 and tethers the HIV preintegration complex to the host genome enabling integration. Recently a new class of IN inhibitors was described, the IN-LEDGF allosteric inhibitors (INLAIs). Designed to interfere with the IN-LEDGF interaction during integration, the major impact of these inhibitors was surprisingly found on virus maturation, causing a reverse transcription defect in target cells. RESULTS: Here we describe the MUT-A compound as a genuine INLAI with an original chemical structure based on a new type of scaffold, a thiophene ring...
November 9, 2017: Retrovirology
https://www.readbyqxmd.com/read/29047401/correction-to-potent-and-reversible-lentiviral-vector-restriction-in-murine-induced-pluripotent-stem-cells
#17
Franziska K Geis, Melanie Galla, Dirk Hoffmann, Johannes Kuehle, Daniela Zychlinski, Tobias Maetzig, Juliane W Schott, Adrian Schwarzer, Christine Goffinet, Stephen P Goff, Axel Schambach
The authors wish to apologize for an error within the scale bar of the microarray heatmap in Additional File 5 of the supplementary information. Two values were incorrectly displayed on the scale bar (11 instead of 10 and 13 instead of 12).
October 18, 2017: Retrovirology
https://www.readbyqxmd.com/read/29037245/reduced-antiretroviral-drug-efficacy-and-concentration-in-hiv-infected-microglia-contributes-to-viral-persistence-in-brain
#18
Eugene L Asahchop, Oussama Meziane, Manmeet K Mamik, Wing F Chan, William G Branton, Lothar Resch, M John Gill, Elie Haddad, Jean V Guimond, Mark A Wainberg, Glen B Baker, Eric A Cohen, Christopher Power
BACKGROUND: In patients with HIV/AIDS receiving antiretroviral therapy (ART), HIV-1 persistence in brain tissue is a vital and unanswered question. HIV-1 infects and replicates in resident microglia and trafficking macrophages within the brain although the impact of individual ART drugs on viral infection within these brain myeloid cells is unknown. Herein, the effects of contemporary ART drugs were investigated using in vitro and in vivo models of HIV-1 brain infection. RESULTS: The EC50 values for specific ART drugs in HIV-infected human microglia were significantly higher compared to bone marrow-derived macrophages and peripheral blood mononuclear cells...
October 16, 2017: Retrovirology
https://www.readbyqxmd.com/read/29017536/a-strongly-selected-mutation-in-the-hiv-1-genome-is-independent-of-t-cell-responses-and-neutralizing-antibodies
#19
Donglai Liu, Chu Wang, Bhavna Hora, Tao Zuo, Nilu Goonetilleke, Michael K P Liu, Mark Berrong, Guido Ferrari, Andrew J McMichael, Tanmoy Bhattacharya, Alan S Perelson, Feng Gao
BACKGROUND: Mutations rapidly accumulate in the HIV-1 genome after infection. Some of those mutations are selected by host immune responses and often cause viral fitness losses. This study is to investigate whether strongly selected mutations that are not associated with immune responses result in fitness losses. RESULTS: Strongly selected mutations were identified by analyzing 5'-half HIV-1 genome (gag/pol) sequences from longitudinal samples of subject CH0131...
October 10, 2017: Retrovirology
https://www.readbyqxmd.com/read/28962653/cellular-fatty-acid-synthase-is-required-for-late-stages-of-hiv-1-replication
#20
Manjusha M Kulkarni, Annette N Ratcliff, Menakshi Bhat, Yazan Alwarawrah, Philip Hughes, Jesus Arcos, David Loiselle, Jordi B Torrelles, Nicholas T Funderburg, Timothy A Haystead, Jesse J Kwiek
BACKGROUND: Like all viruses, HIV-1 relies on host systems to replicate. The human purinome consists of approximately two thousand proteins that bind and use purines such as ATP, NADH, and NADPH. By virtue of their purine binding pockets, purinome proteins are highly druggable, and many existing drugs target purine-using enzymes. Leveraging a protein affinity media that uses the purine-binding pocket to capture the entire purinome, we sought to define purine-binding proteins regulated by HIV-1 infection...
September 29, 2017: Retrovirology
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