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Retrovirology

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https://www.readbyqxmd.com/read/29769116/efficacies-of-cabotegravir-and-bictegravir-against-drug-resistant-hiv-1-integrase-mutants
#1
Steven J Smith, Xue Zhi Zhao, Terrence R Burke, Stephen H Hughes
BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are the class of antiretroviral (ARV) drugs most recently approved by the FDA for the treatment of HIV-1 infections. INSTIs block the strand transfer reaction catalyzed by HIV-1 integrase (IN) and have been shown to potently inhibit infection by wild-type HIV-1. Of the three current FDA-approved INSTIs, Dolutegravir (DTG), has been the most effective, in part because treatment does not readily select for resistant mutants. However, recent studies showed that when INSTI-experienced patients are put on a DTG-salvage therapy, they have reduced response rates...
May 16, 2018: Retrovirology
https://www.readbyqxmd.com/read/29769087/replacement-of-feline-foamy-virus-bet-by-feline-immunodeficiency-virus-vif-yields-replicative-virus-with-novel-vaccine-candidate-potential
#2
Carmen Ledesma-Feliciano, Sarah Hagen, Ryan Troyer, Xin Zheng, Esther Musselman, Dragana Slavkovic Lukic, Ann-Mareen Franke, Daniel Maeda, Jörg Zielonka, Carsten Münk, Guochao Wei, Sue VandeWoude, Martin Löchelt
BACKGROUND: Hosts are able to restrict viral replication to contain virus spread before adaptive immunity is fully initiated. Many viruses have acquired genes directly counteracting intrinsic restriction mechanisms. This phenomenon has led to a co-evolutionary signature for both the virus and host which often provides a barrier against interspecies transmission events. Through different mechanisms of action, but with similar consequences, spumaviral feline foamy virus (FFV) Bet and lentiviral feline immunodeficiency virus (FIV) Vif counteract feline APOBEC3 (feA3) restriction factors that lead to hypermutation and degradation of retroviral DNA genomes...
May 16, 2018: Retrovirology
https://www.readbyqxmd.com/read/29751762/hiv-latency-reversing-agents-act-through-tat-post-translational-modifications
#3
Georges Khoury, Talia M Mota, Shuang Li, Carolin Tumpach, Michelle Y Lee, Jonathan Jacobson, Leigh Harty, Jenny L Anderson, Sharon R Lewin, Damian F J Purcell
BACKGROUND: Different classes of latency reversing agents (LRAs) are being evaluated to measure their effects in reactivating HIV replication from latently infected cells. A limited number of studies have demonstrated additive effects of LRAs with the viral protein Tat in initiating transcription, but less is known about how LRAs interact with Tat, particularly through basic residues that may be post-translationally modified to alter the behaviour of Tat for processive transcription and co-transcriptional RNA processing...
May 11, 2018: Retrovirology
https://www.readbyqxmd.com/read/29716635/clip-related-methodologies-and-their-application-to-retrovirology
#4
REVIEW
Paul D Bieniasz, Sebla B Kutluay
Virtually every step of HIV-1 replication and numerous cellular antiviral defense mechanisms are regulated by the binding of a viral or cellular RNA-binding protein (RBP) to distinct sequence or structural elements on HIV-1 RNAs. Until recently, these protein-RNA interactions were studied largely by in vitro binding assays complemented with genetics approaches. However, these methods are highly limited in the identification of the relevant targets of RBPs in physiologically relevant settings. Development of crosslinking-immunoprecipitation sequencing (CLIP) methodology has revolutionized the analysis of protein-nucleic acid complexes...
May 2, 2018: Retrovirology
https://www.readbyqxmd.com/read/29716624/reconstruction-of-a-replication-competent-ancestral-murine-endogenous-retrovirus-l
#5
Daniel Blanco-Melo, Robert J Gifford, Paul D Bieniasz
BACKGROUND: About 10% of the mouse genome is composed of endogenous retroviruses (ERVs) that represent a molecular fossil record of past retroviral infections. One such retrovirus, murine ERV-L (MuERV-L) is an env-deficient ERV that has undergone episodic proliferation, with the most recent amplification occurring ~ 2 million years ago. MuERV-L related sequences have been co-opted by mice for antiretroviral defense, and possibly as promoters for some genes that regulate totipotency in early mouse embryos...
May 2, 2018: Retrovirology
https://www.readbyqxmd.com/read/29665857/the-htlv-1-oncoprotein-tax-is-modified-by-the-ubiquitin-related-modifier-1-urm1
#6
Rita Hleihel, Behzad Khoshnood, Ingrid Dacklin, Hayssam Omran, Carine Mouawad, Zeina Dassouki, Marwan El-Sabban, Margret Shirinian, Caroline Grabbe, Ali Bazarbachi
BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy secondary to chronic human T-cell lymphotropic virus 1 infection, triggered by the virally encoded oncoprotein Tax. The transforming activity and subcellular localization of Tax is strongly influenced by posttranslational modifications, among which ubiquitylation and SUMOylation have been identified as key regulators of the nuclear/cytoplasmic shuttling of Tax, as well as its ability to activate NF-κB signaling...
April 17, 2018: Retrovirology
https://www.readbyqxmd.com/read/29655366/hiv-1-protease-with-leucine-zipper-fused-at-n-terminus-exhibits-enhanced-linker-amino-acid-dependent-activity
#7
Fu-Hsien Yu, Chin-Tien Wang
BACKGROUND: HIV-1 protease (PR) activation is triggered by Gag-Pol dimerization. Premature PR activation results in reduced virion yields due to enhanced Gag cleavage. A p6* transframe peptide located directly upstream of protease is believed to play a modulating role in PR activation. Previous reports indicate that the C-terminal p6* tetra-peptide prevents premature PR activation triggered by a leucine zipper (LZ) dimerization motif inserted in the deleted p6* region. To clarify the involvement of C-terminal p6* residues in mitigating enhanced LZ-incurred Gag processing, we engineered constructs containing C-terminal p6* residue substitutions with and without a mutation blocking the p6*/PR cleavage site, and created other Gag or p6* domain-removing constructs...
April 14, 2018: Retrovirology
https://www.readbyqxmd.com/read/29636069/new-world-feline-apobec3-potently-controls-inter-genus-lentiviral-transmission
#8
Yoriyuki Konno, Shumpei Nagaoka, Izumi Kimura, Keisuke Yamamoto, Yumiko Kagawa, Ryuichi Kumata, Hirofumi Aso, Mahoko Takahashi Ueda, So Nakagawa, Tomoko Kobayashi, Yoshio Koyanagi, Kei Sato
BACKGROUND: The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) gene family appears only in mammalian genomes. Some A3 proteins can be incorporated into progeny virions and inhibit lentiviral replication. In turn, the lentiviral viral infectivity factor (Vif) counteracts the A3-mediated antiviral effect by degrading A3 proteins. Recent investigations have suggested that lentiviral vif genes evolved to combat mammalian APOBEC3 proteins, and have further proposed that the Vif-A3 interaction may help determine the co-evolutionary history of cross-species lentiviral transmission in mammals...
April 10, 2018: Retrovirology
https://www.readbyqxmd.com/read/29615133/total-hiv-dna-a-global-marker-of-hiv-persistence
#9
REVIEW
Christine Rouzioux, Véronique Avettand-Fenoël
Among the different markers of HIV persistence in infected cells, total HIV DNA is to date the most widely used. It allows an overall quantification of all viral forms of HIV DNA in infected cells, each playing a different role in HIV replication and pathophysiology. The real-time PCR technology is to date, a precise, sensitive and reproducible technology that allows the description of the distribution of HIV infected cells in blood and tissues. The objective of this review is to present some examples which show the interest to quantify total HIV DNA levels...
April 3, 2018: Retrovirology
https://www.readbyqxmd.com/read/29609648/six-helix-bundle-completion-in-the-distal-c-terminal-heptad-repeat-region-of-gp41-is-required-for-efficient-human-immunodeficiency-virus-type-1-infection
#10
Dehua Liu, Hongyun Wang, Mizuki Yamamoto, Jiping Song, Rui Zhang, Qingling Du, Yasushi Kawaguchi, Jun-Ichiro Inoue, Zene Matsuda
BACKGROUND: The native pre-fusion structure of gp120/gp41 complex of human immunodeficiency virus type 1 was recently revealed. In the model, the helices of gp41 (α6, α7, α8, and α9) form a four-helix collar underneath trimeric gp120. Gp41 is a class I fusion protein and mediates membrane fusion by forming a post-fusion structure called the six-helix bundle (6HB). The comparison of the pre- and post-fusion structures revealed the large conformational changes in gp41 during the antiparallel packing of the N- and C-terminal heptad repeats (NHRs and CHRs) in membrane fusion...
April 2, 2018: Retrovirology
https://www.readbyqxmd.com/read/29609635/why-was-perv-not-transmitted-during-preclinical-and-clinical-xenotransplantation-trials-and-after-inoculation-of-animals
#11
REVIEW
Joachim Denner
Porcine endogenous retroviruses (PERVs) are present in the genome of all pigs, they infect certain human cells and therefore pose a special risk for xenotransplantation using pig cells, tissues and organs. Xenotransplantation is being developed in order to alleviate the reduced availability of human organs. Despite the fact that PERVs are able to infect certain human cells and cells from other species, transmission of PERVs has not been observed when animals (including non-human primates) were inoculated with PERV preparations or during preclinical xenotransplantations...
April 2, 2018: Retrovirology
https://www.readbyqxmd.com/read/29609619/pre-exposure-prophylaxis-prep-in-an-era-of-stalled-hiv-prevention-can-it-change-the-game
#12
REVIEW
Robyn Eakle, Francois Venter, Helen Rees
Pre-exposure prophylaxis (PrEP) for HIV prevention has evolved significantly over the years where clinical trials have now demonstrated the efficacy of oral PrEP, and the field is scaling-up implementation. The WHO and UNAIDS have made PrEP implementation a priority for populations at highest risk, and several countries have developed guidelines and national plans accordingly, largely based on evidence generated by demonstration projects. PrEP presents the opportunity to change the face of HIV prevention by offering a new option for protection against HIV and disrupting current HIV prevention systems...
April 2, 2018: Retrovirology
https://www.readbyqxmd.com/read/29554922/a-crispr-screen-for-factors-regulating-samhd1-degradation-identifies-ifitms-as-potent-inhibitors-of-lentiviral-particle-delivery
#13
Ferdinand Roesch, Molly OhAinle, Michael Emerman
The InterFeron Induced TransMembrane (IFITM) proteins are interferon stimulated genes that restrict many viruses, including HIV-1. SAMHD1 is another restriction factor blocking replication of HIV-1 and other viruses. Some lentiviruses evolved Vpx/Vpr proteins to degrade SAMHD1. However, this viral antagonism can be perturbed by host mechanisms: a recent study showed that in interferon (IFN) treated THP1 cells, Vpx is unable to degrade SAMHD1. In the present work, we designed an Interferon Stimulated Genes (ISGs)-targeted CRISPR knockout screen in order to identify ISGs regulating this phenotype...
March 20, 2018: Retrovirology
https://www.readbyqxmd.com/read/29540207/an-rna-binding-compound-that-stabilizes-the-hiv-1-grna-packaging-signal-structure-and-specifically-blocks-hiv-1-rna-encapsidation
#14
Carin K Ingemarsdotter, Jingwei Zeng, Ziqi Long, Andrew M L Lever, Julia C Kenyon
BACKGROUND: NSC260594, a quinolinium derivative from the NCI diversity set II compound library, was previously identified in a target-based assay as an inhibitor of the interaction between the HIV-1 (ψ) stem-loop 3 (SL3) RNA and Gag. This compound was shown to exhibit potent antiviral activity. Here, the effects of this compound on individual stages of the viral lifecycle were examined by qRT-PCR, ELISA and Western blot, to see if its actions were specific to the viral packaging stage...
March 14, 2018: Retrovirology
https://www.readbyqxmd.com/read/29523166/predominant-envelope-variable-loop-2-specific-and-gp120-specific-antibody-dependent-cellular-cytotoxicity-antibody-responses-in-acutely-siv-infected-african-green-monkeys
#15
Quang N Nguyen, David R Martinez, Jonathon E Himes, R Whitney Edwards, Qifeng Han, Amit Kumar, Riley Mangan, Nathan I Nicely, Guanhua Xie, Nathan Vandergrift, Xiaoying Shen, Justin Pollara, Sallie R Permar
BACKGROUND: The initial envelope (Env)-specific antibody response in acutely HIV-1-infected individuals and simian immunodeficiency virus (SIV)-infected rhesus monkeys (RMs) is dominated by non-neutralizing antibodies targeting Env gp41. In contrast, natural primate SIV hosts, such as African green monkeys (AGMs), develop a predominant Env gp120-specific antibody response to SIV infection. However, the fine-epitope specificity and function of SIV Env-specific plasma IgG, and their potential role on autologous virus co-evolution in SIV-infected AGMs and RMs remain unclear...
March 9, 2018: Retrovirology
https://www.readbyqxmd.com/read/29471854/recent-advances-in-retroviruses-via-cryo-electron-microscopy
#16
REVIEW
Johnson Mak, Alex de Marco
Cryo-electron microscopy has undergone a revolution in recent years and it has contributed significantly to a number of different areas in biological research. In this manuscript, we will describe some of the recent advancements in cryo-electron microscopy focussing on the advantages that this technique can bring rather than on the technology. We will then conclude discussing how the field of retrovirology has benefited from cryo-electron microscopy.
February 23, 2018: Retrovirology
https://www.readbyqxmd.com/read/29452580/measuring-integrated-hiv-dna-ex-vivo-and-in-vitro-provides-insights-about-how-reservoirs-are-formed-and-maintained
#17
REVIEW
Marilia Rita Pinzone, Una O'Doherty
The identification of the most appropriate marker to measure reservoir size has been a great challenge for the HIV field. Quantitative viral outgrowth assay (QVOA), the reference standard to quantify the amount of replication-competent virus, has several limitations, as it is laborious, expensive, and unable to robustly reactivate every single integrated provirus. PCR-based assays have been developed as an easier, cheaper and less error-prone alternative to QVOA, but also have limitations. Historically, measuring integrated HIV DNA has provided insights about how reservoirs are formed and maintained...
February 17, 2018: Retrovirology
https://www.readbyqxmd.com/read/29433524/measuring-replication-competent-hiv-1-advances-and-challenges-in-defining-the-latent-reservoir
#18
REVIEW
Zheng Wang, Francesco R Simonetti, Robert F Siliciano, Gregory M Laird
Antiretroviral therapy cannot cure HIV-1 infection due to the persistence of a small number of latently infected cells harboring replication-competent proviruses. Measuring persistent HIV-1 is challenging, as it consists of a mosaic population of defective and intact proviruses that can shift from a state of latency to active HIV-1 transcription. Due to this complexity, most of the current assays detect multiple categories of persistent HIV-1, leading to an overestimate of the true size of the latent reservoir...
February 13, 2018: Retrovirology
https://www.readbyqxmd.com/read/29426337/non-coding-rnas-and-retroviruses
#19
REVIEW
Xu Zhang, Xiancai Ma, Shuliang Jing, Hui Zhang, Yijun Zhang
Retroviruses can cause severe diseases such as cancer and acquired immunodeficiency syndrome. A unique feature in the life cycle of retroviruses is that their RNA genome is reverse transcribed into double-stranded DNA, which then integrates into the host genome to exploit the host machinery for their benefits. The metazoan genome encodes numerous non-coding RNAs (ncRNA), which act as key regulators in essential cellular processes such as antiviral response. The development of next-generation sequencing technology has greatly accelerated the detection of ncRNAs from viruses and their hosts...
February 9, 2018: Retrovirology
https://www.readbyqxmd.com/read/29402305/assessment-of-the-gorilla-gut-virome-in-association-with-natural-simian-immunodeficiency-virus-infection
#20
Mirela D'arc, Carolina Furtado, Juliana D Siqueira, Héctor N Seuánez, Ahidjo Ayouba, Martine Peeters, Marcelo A Soares
BACKGROUND: Simian immunodeficiency viruses (SIVs) of chimpanzees and gorillas from Central Africa crossed the species barrier at least four times giving rise to human immunodeficiency virus type 1 (HIV-1) groups M, N, O and P. The paradigm of non-pathogenic lentiviral infections has been challenged by observations of naturally infected chimpanzees with SIVcpz associated with a negative impact on their life span and reproduction, CD4+ T-lymphocyte loss and lymphoid tissue destruction...
February 5, 2018: Retrovirology
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