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Retrovirology

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https://www.readbyqxmd.com/read/29141633/genome-modification-of-cxcr4-by-staphylococcus-aureus-cas9-renders-cells-resistance-to-hiv-1-infection
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28938888/unique-binding-modes-for-the-broad-neutralizing-activity-of-single-chain-variable-fragments-scfv-targeting-cd4-induced-epitopes
#8
Kazuki Tanaka, Takeo Kuwata, Muntasir Alam, Gilad Kaplan, Shokichi Takahama, Kristel Paola Ramirez Valdez, Anna Roitburd-Berman, Jonathan M Gershoni, Shuzo Matsushita
BACKGROUND: The CD4-induced (CD4i) epitopes in gp120 includes the co-receptor binding site, which are formed and exposed after interaction with CD4. Monoclonal antibodies (mAbs) to the CD4i epitopes exhibit limited neutralizing activity because of restricted access to their epitopes. However, small fragment counterparts such as single-chain variable fragments (scFvs) have been reported to neutralize a broad range of viruses compared with the full-size IgG molecule. To identify the CD4i epitope site responsible for this broad neutralization we constructed three scFvs of anti-CD4i mAbs from a human immunodeficiency virus type 1 (HIV-1)-infected elite controller, and investigated the neutralization coverage and precise binding site in the CD4i epitopes...
September 22, 2017: Retrovirology
https://www.readbyqxmd.com/read/28870251/hiv-1-tolerates-changes-in-a-count-in-a-small-segment-of-the-pol-gene
#9
Bep Klaver, Yme van der Velden, Formijn van Hemert, Antoinette C van der Kuyl, Ben Berkhout
BACKGROUND: The HIV-1 RNA genome has a biased nucleotide composition with a surplus of As. Several hypotheses have been put forward to explain this striking phenomenon, but the A-count of the HIV-1 genome has thus far not been systematically manipulated. The reason for this reservation is the likelihood that known and unknown sequence motifs will be affected by such a massive mutational approach, thus resulting in replication-impaired virus mutants. We present the first attempt to increase and decrease the A-count in a relatively small polymerase (pol) gene segment of HIV-1 RNA...
September 5, 2017: Retrovirology
https://www.readbyqxmd.com/read/28835242/granulocytic-myeloid-derived-suppressor-cells-suppress-virus-specific-cd8-t-cell-responses-during-acute-friend-retrovirus-infection
#10
Malgorzata Drabczyk-Pluta, Tanja Werner, Daniel Hoffmann, Qibin Leng, Lieping Chen, Ulf Dittmer, Gennadiy Zelinskyy
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) can suppress T cell responses in several different diseases. Previously these suppressive cells were observed to expand in HIV patients and in a mouse retrovirus model, yet their suppressive effect on virus-specific CD8(+) T cells in vitro and in vivo has not been characterized thus far. RESULTS: We used the Friend retrovirus (FV) model to demonstrate that MDSCs expand and become activated during the late phase of acute FV infection...
August 23, 2017: Retrovirology
https://www.readbyqxmd.com/read/28830571/anti-herv-k-hml-2-capsid-antibody-responses-in-hiv-elite-controllers
#11
Miguel de Mulder, Devi SenGupta, Steven G Deeks, Jeffrey N Martin, Christopher D Pilcher, Frederick M Hecht, Jonah B Sacha, Douglas F Nixon, Henri-Alexandre Michaud
BACKGROUND: Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection. RESULTS: We developed an ELISA assay using either recombinant protein or 164 redundant "15mer" HERV-K (HML-2) Gag peptides to test sera for antibody reactivity...
August 22, 2017: Retrovirology
https://www.readbyqxmd.com/read/28830558/identification-of-a-homogenous-structural-basis-for-oligomerization-by-retroviral-rev-like-proteins
#12
Chijioke N Umunnakwe, Karin S Dorman, Drena Dobbs, Susan Carpenter
BACKGROUND: Rev-like proteins are post-transcriptional regulatory proteins found in several retrovirus genera, including lentiviruses, betaretroviruses, and deltaretroviruses. These essential proteins mediate the nuclear export of incompletely spliced viral RNA, and act by tethering viral pre-mRNA to the host CRM1 nuclear export machinery. Although all Rev-like proteins are functionally homologous, they share less than 30% sequence identity. In the present study, we computationally assessed the extent of structural homology among retroviral Rev-like proteins within a phylogenetic framework...
August 22, 2017: Retrovirology
https://www.readbyqxmd.com/read/28754126/modulation-of-chromatin-structure-by-the-fact-histone-chaperone-complex-regulates-hiv-1-integration
#13
Julien Matysiak, Paul Lesbats, Eric Mauro, Delphine Lapaillerie, Jean-William Dupuy, Angelica P Lopez, Mohamed Salah Benleulmi, Christina Calmels, Marie-Line Andreola, Marc Ruff, Manuel Llano, Olivier Delelis, Marc Lavigne, Vincent Parissi
BACKGROUND: Insertion of retroviral genome DNA occurs in the chromatin of the host cell. This step is modulated by chromatin structure as nucleosomes compaction was shown to prevent HIV-1 integration and chromatin remodeling has been reported to affect integration efficiency. LEDGF/p75-mediated targeting of the integration complex toward RNA polymerase II (polII) transcribed regions ensures optimal access to dynamic regions that are suitable for integration. Consequently, we have investigated the involvement of polII-associated factors in the regulation of HIV-1 integration...
July 28, 2017: Retrovirology
https://www.readbyqxmd.com/read/28659190/tribute-to-mark-wainberg
#14
Eric J Arts, Anne Gatignol, Andrew J Mouland, Chen Liang, Matthias Götte, Hugo Soudeyns
No abstract text is available yet for this article.
June 28, 2017: Retrovirology
https://www.readbyqxmd.com/read/28637466/the-kt-jeang-retrovirology-prize-2017-michael-emerman
#15
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
June 21, 2017: Retrovirology
https://www.readbyqxmd.com/read/28583191/hiv-drug-resistance-against-strand-transfer-integrase-inhibitors
#16
REVIEW
Kaitlin Anstett, Bluma Brenner, Thibault Mesplede, Mark A Wainberg
Integrase strand transfer inhibitors (INSTIs) are the newest class of antiretroviral drugs to be approved for treatment and act by inhibiting the essential HIV protein integrase from inserting the viral DNA genome into the host cell's chromatin. Three drugs of this class are currently approved for use in HIV-positive individuals: raltegravir (RAL), elvitegravir (EVG), and dolutegravir (DTG), while cabotegravir (CAB) and bictegravir (BIC) are currently in clinical trials. RAL and EVG have been successful in clinical settings but have relatively low genetic barriers to resistance...
June 5, 2017: Retrovirology
https://www.readbyqxmd.com/read/28576126/effective-treatment-of-sivcpz-induced-immunodeficiency-in-a-captive-western-chimpanzee
#17
Hannah J Barbian, Raven Jackson-Jewett, Corrine S Brown, Frederic Bibollet-Ruche, Gerald H Learn, Timothy Decker, Edward F Kreider, Yingying Li, Thomas N Denny, Paul M Sharp, George M Shaw, Jeffrey Lifson, Edward P Acosta, Michael S Saag, Katharine J Bar, Beatrice H Hahn
BACKGROUND: Simian immunodeficiency virus of chimpanzees (SIVcpz), the progenitor of human immunodeficiency virus type 1 (HIV-1), is associated with increased mortality and AIDS-like immunopathology in wild-living chimpanzees (Pan troglodytes). Surprisingly, however, similar findings have not been reported for chimpanzees experimentally infected with SIVcpz in captivity, raising questions about the intrinsic pathogenicity of this lentivirus. FINDINGS: Here, we report progressive immunodeficiency and clinical disease in a captive western chimpanzee (P...
June 2, 2017: Retrovirology
https://www.readbyqxmd.com/read/28569216/potent-and-reversible-lentiviral-vector-restriction-in-murine-induced-pluripotent-stem-cells
#18
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
BACKGROUND: Retroviral vectors are derived from wild-type retroviruses, can be used to study retrovirus-host interactions and are effective tools in gene and cell therapy. However, numerous cell types are resistant or less permissive to retrovirus infection due to the presence of active defense mechanisms, or the absence of important cellular host co-factors. In contrast to multipotent stem cells, pluripotent stem cells (PSC) have potential to differentiate into all three germ layers...
May 31, 2017: Retrovirology
https://www.readbyqxmd.com/read/28535768/parent-offspring-regression-to-estimate-the-heritability-of-an-hiv-1-trait-in-a-realistic-setup
#19
Nadine Bachmann, Teja Turk, Claus Kadelka, Alex Marzel, Mohaned Shilaih, Jürg Böni, Vincent Aubert, Thomas Klimkait, Gabriel E Leventhal, Huldrych F Günthard, Roger Kouyos
BACKGROUND: Parent-offspring (PO) regression is a central tool to determine the heritability of phenotypic traits; i.e., the relative extent to which those traits are controlled by genetic factors. The applicability of PO regression to viral traits is unclear because the direction of viral transmission-who is the donor (parent) and who is the recipient (offspring)-is typically unknown and viral phylogenies are sparsely sampled. METHODS: We assessed the applicability of PO regression in a realistic setting using Ornstein-Uhlenbeck simulated data on phylogenies built from 11,442 Swiss HIV Cohort Study (SHCS) partial pol sequences and set-point viral load (SPVL) data from 3293 patients...
May 23, 2017: Retrovirology
https://www.readbyqxmd.com/read/28532477/jan-svoboda-1934-2017-sixty-years-with-retroviruses
#20
LETTER
Jiří Hejnar
No abstract text is available yet for this article.
May 22, 2017: Retrovirology
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