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HIV genomics

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https://www.readbyqxmd.com/read/28817720/targeting-of-cdk9-with-indirubin-3-monoxime-safely-and-durably-reduces-hiv-viremia-in-chronically-infected-humanized-mice
#1
Sandra Medina-Moreno, Thomas C Dowling, Juan C Zapata, Nhut M Le, Edward Sausville, Joseph Bryant, Robert R Redfield, Alonso Heredia
Successful propagation of HIV in the human host requires entry into a permissive cell, reverse transcription of viral RNA, integration into the human genome, transcription of the integrated provirus, and assembly/release of new virus particles. Currently, there are antiretrovirals against each of these viral steps, except for provirus transcription. An inhibitor of HIV transcription could both increase potency of treatment and suppress drug-resistant strains. Cellular cyclin-dependent kinase 9 (CDK9) serves as a cofactor for the HIV Tat protein and is required for effective transcription of the provirus...
2017: PloS One
https://www.readbyqxmd.com/read/28814526/hiv-1-exploits-dynamic-multi-aminoacyl-trna-synthetase-complex-to-enhance-viral-replication
#2
Alice A Duchon, Corine St-Gelais, Nathan Titkemeier, Joshua Hatterschide, Li Wu, Karin Musier-Forsyth
A hallmark of retroviruses such as human immunodeficiency virus type 1 (HIV-1) is reverse transcription of genomic RNA to DNA, a process that is primed by cellular tRNAs. HIV-1 recruits human tRNA(Lys3) to serve as the reverse transcription primer via an interaction between lysyl-tRNA synthetase (LysRS) and the HIV-1 Gag polyprotein. LysRS is normally sequestered in a multi-aminoacyl-tRNA synthetase complex (MSC). Previous studies demonstrated that components of the MSC can be mobilized in response to certain cellular stimuli, but how LysRS is redirected from the MSC to viral particles for packaging is unknown...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28811638/the-cpg-dinucleotide-content-of-the-hiv-1-envelope-gene-may-predict-disease-progression
#3
Mishi Kaushal Wasson, Jayanta Borkakoti, Amit Kumar, Banhi Biswas, Perumal Vivekanandan
The clinical course of HIV-1 varies greatly among infected individuals. Despite extensive research, virus factors associated with slow-progression remain poorly understood. Identification of unique HIV-1 genomic signatures linked to slow-progression remains elusive. We investigated CpG dinucleotide content in HIV-1 envelope gene as a potential virus factor in disease progression. We analysed 1808 HIV-1 envelope gene sequences from three independent longitudinal studies; this included 1280 sequences from twelve typical-progressors and 528 sequences from six slow-progressors...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811349/brain-macrophages-in-simian-immunodeficiency-virus-infected-antiretroviral-suppressed-macaques-a-functional-latent-reservoir
#4
Claudia R Avalos, Celina M Abreu, Suzanne E Queen, Ming Li, Sarah Price, Erin N Shirk, Elizabeth L Engle, Ellen Forsyth, Brandon T Bullock, Feilim Mac Gabhann, Stephen W Wietgrefe, Ashley T Haase, M Christine Zink, Joseph L Mankowski, Janice E Clements, Lucio Gama
A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring virus that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation and neuronal damage in cerebrospinal fluid (CSF) of HIV-infected individuals demonstrate continued effects of HIV in brain and suggest that the central nervous system (CNS) may serve as a viral reservoir...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28806866/molecular-screening-and-single-nucleotide-polymorphism-typing-of-molluscum-contagiosum-virus-mcv-from-genital-specimens-between-2012-and-2015
#5
Sedigheh Taghinezhad-S, Amir Hossein Mohseni, Hossein Keyvani, Narges Ghobadi
Background: The present study is the first comprehensive report of the Molluscum contagiosum virus (MCV) in Iran based on the molecular technique for differentiation and typing of the MCV1 and MCV2. Methods: Patients were diagnosed as having tumor-like genital warts less than 5 mm in diameter, and HIV seronegative samples were chosen for this cross-sectional study. TaqMan real-time PCR was used to identify MCV following clinical examination. Typing of the MCV-positive specimens was performed in the SNP A27451G region of MC021L gene...
August 15, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28800335/an-overview-of-human-immunodeficiency-virus-type-1-associated-common-neurological-complications-does-aging-pose-a-challenge
#6
Anantha Ram Nookala, Joy Mitra, Nitish S Chaudhari, Muralidhar L Hegde, Anil Kumar
With increasing survival of patients infected with human immunodeficiency virus type 1 (HIV-1), the manifestation of heterogeneous neurological complications is also increasing alarmingly in these patients. Currently, more than 30% of about 40 million HIV-1 infected people worldwide develop central nervous system (CNS)-associated dysfunction, including dementia, sensory, and motor neuropathy. Furthermore, the highly effective antiretroviral therapy has been shown to increase the prevalence of mild cognitive functions while reducing other HIV-1-associated neurological complications...
August 9, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28793783/characterization-of-a-novel-hiv-1-second-generation-recombinant-form-in-men-who-have-sex-with-men-in-beijing-china
#7
Chen Wang, Yan Wang, Desheng Kong, Ruolei Xin, Weisi Xu, Yi Feng, Yiming Shao, Liying Ma
Co-circulation of multiple subtypes in same population contributes significantly to the emergence of recombinant viruses. BJ2015EU19, a novel CCR5-tropic HIV-1 second-generation recombinant virus,was isolated from a man who has sex with man in Beijing, China. Phylogenetic analysis of the near full-length genome showed that BJ2015EU19 was consisted of seven fragments from CRF01_AE and CRF07_BC. There were six recombinant breakpoints in the pol, vpu, env and nef genes of BJ2015EU19,which were different from the other circulating recombinant forms and unique recombinant forms...
August 10, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28774988/draft-genome-sequence-of-mycobacterium-peregrinum-isolated-from-an-hiv-positive-patient-in-south-africa
#8
Shaheed V Omar, Mushal Allam, Lavania Joseph, Senzo Mtshali, Nazir A Ismail, Arshad Ismail
Here, we report a draft genome sequence of Mycobacterium peregrinum obtained from a sputum sample of a South African HIV-infected patient with suspected pulmonary tuberculosis. The genome described here comprises 6,931,852 bp, revealing 66.2% G+C content, 6,808 coding sequences, and 81 RNA genes.
August 3, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28762410/accurate-nanoscale-flexibility-measurement-of-dna-and-dna-protein-complexes-by-atomic-force-microscopy-in-liquid
#9
Divakaran Murugesapillai, Serge Bouaziz, L James Maher, Nathan E Israeloff, Craig E Cameron, Mark C Williams
The elasticity of double-stranded DNA (dsDNA), as described by its persistence length, is critical for many biological processes, including genomic regulation. A persistence length value can be obtained using atomic force microscopy (AFM) imaging. However, most AFM studies have been done by depositing the sample on a surface using adhesive ligands and fitting the contour to a two-dimensional (2D) wormlike chain (WLC) model. This often results in a persistence length measurement that is different from the value determined using bulk and single molecule methods...
August 1, 2017: Nanoscale
https://www.readbyqxmd.com/read/28760348/crispr-cas-based-antiviral-strategies-against-hiv-1
#10
REVIEW
Gang Wang, Na Zhao, Ben Berkhout, Atze T Das
In bacteria and archaea, the clustered regularly interspaced short palindromic repeats (CRISPR) and associated proteins (Cas) confer adaptive immunity against exogenous DNA elements. This CRISPR-Cas system has been turned into an effective tool for editing of eukaryotic DNA genomes. Pathogenic viruses that have a double-stranded DNA (dsDNA) genome or that replicate through a dsDNA intermediate can also be targeted with this DNA editing tool. Here, we review how CRISPR-Cas was used in novel therapeutic approaches against the human immunodeficiency virus type-1 (HIV-1), focusing on approaches that aim to permanently inactivate all virus genomes or to prevent viral persistence in latent reservoirs...
July 28, 2017: Virus Research
https://www.readbyqxmd.com/read/28754126/modulation-of-chromatin-structure-by-the-fact-histone-chaperone-complex-regulates-hiv-1-integration
#11
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/28747624/number-of-infection-events-per-cell-during-hiv-1-cell-free-infection
#12
Yusuke Ito, Azaria Remion, Alexandra Tauzin, Keisuke Ejima, Shinji Nakaoka, Yoh Iwasa, Shingo Iwami, Fabrizio Mammano
HIV-1 accumulates changes in its genome through both recombination and mutation during the course of infection. For recombination to occur, a single cell must be infected by two HIV strains. These coinfection events were experimentally demonstrated to occur more frequently than would be expected for independent infection events and do not follow a random distribution. Previous mathematical modeling approaches demonstrated that differences in target cell susceptibility can explain the non-randomness, both in the context of direct cell-to-cell transmission, and in the context of free virus transmission (Q...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747499/effects-of-the-inner-nuclear-membrane-proteins-sun1-unc-84a-and-sun2-unc-84b-on-the-early-steps-of-hiv-1-infection
#13
Torsten Schaller, Lorenzo Bulli, Darja Pollpeter, Gilberto Betancor, Juliane Kutzner, Luis Apolonia, Nikolas Herold, Robin Burk, Michael H Malim
Human immunodeficiency virus type 1 (HIV-1) infection of dividing and non-dividing cells involves regulatory interactions with the nuclear pore complex (NPC), followed by translocation to the nucleus and preferential integration into genomic areas in proximity to the inner nuclear membrane (INM). To identify host proteins that may contribute to these processes, we performed an overexpression screen of known membrane-associated NE proteins. We found that the integral transmembrane proteins SUN1/UNC84A and SUN2/UNC84B are potent or modest inhibitors of HIV-1 infection, respectively, and that suppression corresponds to defects in the accumulation of viral cDNA in the nucleus...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28745207/hiv-drug-resistance-testing-in-a-resource-limited-setting-with-high-viral-diversity-the-first-twenty-eight-months-experience
#14
Elodie Teclaire Ngo-Malabo, Paul Alain Ngoupo, Serge Alain Sadeuh-Mba, Emmanuel Akongnwi, Robert Banaï, Laure Ngono, Richard Njouom, Charles Felix Bilong-Bilong, Anfumbom Kfutwah
BACKGROUND: First line antiretroviral therapy in a resource-limited setting consists of nucleotide and non-nucleotide reverse transcriptase inhibitors. Protease inhibitors are the hub of second line therapy. The decision to change antiretroviral therapy for a patient is frequently presumptive because of the lack of genotypic resistance tests in routine follow-up. We describe here the resistance profiles observed in patients with varying terms of antiretroviral therapy in Cameroon after implementation of HIV genotypic resistance testing in routine practice...
July 25, 2017: Current HIV Research
https://www.readbyqxmd.com/read/28744024/recent-increased-identification-and-transmission-of-hiv-1-unique-recombinant-forms-in-sweden
#15
Ujjwal Neogi, Abu Bakar Siddik, Prabhav Kalaghatgi, Magnus Gisslén, Göran Bratt, Gaetano Marrone, Anders Sönnerborg
A temporal increase in non-B subtypes has earlier been described in Sweden by us and we hypothesized that this increased viral heterogeneity may become a hotspot for the development of more complex and unique recombinant forms (URFs) if the epidemics converge. In the present study, we performed subtyping using four automated tools and phylogenetic analysis by RAxML of pol gene sequences (n = 5246) and HIV-1 near full-length genome (HIV-NFLG) sequences (n = 104). A CD4(+) T-cell decline trajectory algorithm was used to estimate time of HIV infection...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28737979/hect-domain-and-rcc1-like-domain-containing-protein-5-herc-5-gene-polymorphisms-in-hiv-1-infected-individuals-a-study-from-india
#16
Nawaj Shaikh, Vandana Saxena, Sudhanshu Pandey, Ajit Patil, Madhuri Thakar
HECT domain and RCC1-like domain-containing protein 5 (HERC-5) is one of the novel host restriction factors that is known to inhibit HIV release in vitro. Polymorphisms in other host restriction factors have been associated with HIV infection and disease progression. However, no report is available on the HERC-5 polymorphism in HIV-infected individuals. We studied the HERC-5 gene polymorphism in HIV-infected individuals and explored whether it is associated with different disease outcomes. Genomic DNA was isolated from 41 HIV-1 progressors, 39 long-term nonprogressors, and 74 HIV seronegative healthy donors for amplification of HERC5 Exon-18 and other regulatory regions followed by sequencing...
July 24, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28732051/cd4-is-expressed-on-a-heterogeneous-subset-of-hematopoietic-progenitors-which-persistently-harbor-cxcr4-and-ccr5-tropic-hiv-proviral-genomes-in-vivo
#17
Nadia T Sebastian, Thomas D Zaikos, Valeri Terry, Frances Taschuk, Lucy A McNamara, Adewunmi Onafuwa-Nuga, Ryan Yucha, Robert A J Signer, James Riddell Iv, Dale Bixby, Norman Markowitz, Sean J Morrison, Kathleen L Collins
Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor cells are a heterogeneous population of cells, some of which are long-lived. CXCR4-tropic HIVs infect a broad range of HSPC subtypes, including hematopoietic stem cells, which are multi-potent and long-lived. However, CCR5-tropic HIV infection is limited to more differentiated progenitor cells with life spans that are less well understood. Consistent with emerging data that restricted progenitor cells can be long-lived, we detected persistent HIV in restricted HSPC populations from optimally treated people...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28729655/a-crispr-cas9-guidance-rna-screen-platform-for-hiv-provirus-disruption-and-hiv-aids-gene-therapy-in-astrocytes
#18
Zaohua Huang, Madahavan Nair
HIV/AIDS remains a major health threat despite significant advances in the prevention and treatment of HIV infection. The major reason is the inability of existing treatments to eradicate the multiple HIV reservoirs in the human body, including astrocytes in the human brain. CRISPR/Cas9 system is an emerging gene-editing technique with the potential to eliminate or disrupt HIV provirus in HIV reservoir cells, which may lead to a complete cure of HIV/AIDS. The key components of CRISPR/Cas9 are guide RNAs (gRNAs) which determine specific sequence targeting of DNAs...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28726630/dissection-of-specific-binding-of-hiv-1-gag-to-the-packaging-signal-in-viral-rna
#19
Mauricio Comas-Garcia, Siddhartha Ak Datta, Laura Baker, Rajat Varma, Prabhakar R Gudla, Alan Rein
Selective packaging of HIV-1 genomic RNA (gRNA) requires the presence of a cis-acting RNA element called the 'packaging signal' (Ψ). However, the mechanism by which Ψ promotes selective packaging of the gRNA is not well understood. We used fluorescence correlation spectroscopy and quenching data to monitor the binding of recombinant HIV-1 Gag protein to Cy5-tagged 190-base RNAs. At physiological ionic strength, Gag binds with very similar, nanomolar affinities to both Ψ-containing and control RNAs. We challenged these interactions by adding excess competing tRNA; introducing mutations in Gag; or raising the ionic strength...
July 20, 2017: ELife
https://www.readbyqxmd.com/read/28712312/near-full-length-genome-sequence-of-a-novel-hiv-1-second-generation-recombinant-form-crf01_ae-crf07_bc-detected-among-blood-donors-in-north-china
#20
Wei He, Xiaoxu Han, Minghui An, Yanqiu Hai, Le Chang, Chao Liu, Lunan Wang, Hong Shang
In this study, a novel CRF01_AE/07_BC HIV-1 recombinant form, with five breakpoints in the pol, vpr, env, and nef gene regions, was identified from a voluntary blood donor in North China. Our study showed that this HIV-1 recombinant form might be a second-generation recombinant form from two predominant strains in the men who have sex with men (MSM) population, with the CRF07_BC fragments belonging to a CRF07_BC lineage specific to Chinese MSM and the CRF01_AE fragments belonging to the CRF01_AE lineage 5 common among MSM in northern China...
August 16, 2017: AIDS Research and Human Retroviruses
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