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HIV genomics

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https://www.readbyqxmd.com/read/28228523/vpx-overcomes-a-samhd1-independent-block-to-hiv-reverse-transcription-that-is-specific-to-resting-cd4-t-cells
#1
Hanna-Mari Baldauf, Lena Stegmann, Sarah-Marie Schwarz, Ina Ambiel, Maud Trotard, Margarethe Martin, Manja Burggraf, Gina M Lenzi, Helena Lejk, Xiaoyu Pan, Oliver I Fregoso, Efrem S Lim, Libin Abraham, Laura A Nguyen, Frank Rutsch, Renate König, Baek Kim, Michael Emerman, Oliver T Fackler, Oliver T Keppler
Early after entry into monocytes, macrophages, dendritic cells, and resting CD4 T cells, HIV encounters a block, limiting reverse transcription (RT) of the incoming viral RNA genome. In this context, dNTP triphosphohydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, lowering the concentration of dNTP substrates to limit RT. The accessory lentiviral protein X (Vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, sooty mangabey, and HIV-2 (SIVsmm/SIVmac/HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellular dNTP pools, and facilitate HIV cDNA synthesis...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28225830/ex-vivo-activation-of-cd4-t-cells-from-donors-on-suppressive-art-can-lead-to-sustained-production-of-infectious-hiv-1-from-a-subset-of-infected-cells
#2
John K Bui, Elias K Halvas, Elizabeth Fyne, Michele D Sobolewski, Dianna Koontz, Wei Shao, Brian Luke, Feiyu F Hong, Mary F Kearney, John W Mellors
The fate of HIV-infected cells after reversal of proviral latency is not well characterized. Simonetti, et al. recently showed that CD4+ T-cells containing intact proviruses can clonally expand in vivo and produce low-level infectious viremia. We hypothesized that reversal of HIV latency by activation of CD4+ T-cells can lead to the expansion of a subset of virus-producing cells rather than their elimination. We established an ex vivo cell culture system involving stimulation of CD4+ T-cells from donors on suppressive antiretroviral therapy (ART) with PMA/ionomycin (day 1-7), followed by rest (day 7-21), and then repeat stimulation (day 21-28), always in the presence of high concentrations of raltegravir and efavirenz to effectively block new cycles of viral replication...
February 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28222188/the-thermodynamics-of-pr55gag-rna-interaction-regulate-the-assembly-of-hiv
#3
Hanumant S Tanwar, Keith K Khoo, Megan Garvey, Lynne Waddington, Andrew Leis, Marcel Hijnen, Tony Velkov, Geoff J Dumsday, William J McKinstry, Johnson Mak
The interactions that occur during HIV Pr55Gag oligomerization and genomic RNA packaging are essential elements that facilitate HIV assembly. However, mechanistic details of these interactions are not clearly defined. Here, we overcome previous limitations in producing large quantities of full-length recombinant Pr55Gag that is required for isothermal titration calorimetry (ITC) studies, and we have revealed the thermodynamic properties of HIV assembly for the first time. Thermodynamic analysis showed that the binding between RNA and HIV Pr55Gag is an energetically favourable reaction (ΔG<0) that is further enhanced by the oligomerization of Pr55Gag...
February 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28218480/human-leucocyte-antigen-hla-dqb1-03-02-and-hla-a-02-01-have-opposite-patterns-in-their-effects-on-susceptibility-to-hiv-infection
#4
N Rallón, C Restrepo, J L Vicario, J Del Romero, C Rodríguez, J García-Samaniego, M García, A Cabello, M Górgolas, J M Benito
OBJECTIVES: The objective of this study was to seek correlates of immune protection in HIV infection. We sought to elucidate the association between the presence of human leucocyte antigen (HLA) alleles, as well as killer immunoglobulin receptor (KIR) genotypes, and the susceptibility to HIV infection in a Spanish cohort of HIV-exposed seronegative (HESN) individuals. METHODS: A total of 152 individuals were evaluated: 29 HESN individuals in stable heterosexual relationships with an HIV-infected partner admitting high-risk sexual intercourse for at least 12 months prior to inclusion in the study, 61 HIV-infected patients and 62 healthy controls...
February 20, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28210784/novel-aids-therapies-based-on-gene-editing
#5
REVIEW
Kamel Khalili, Martyn K White, Jeffrey M Jacobson
HIV/AIDS remains a major public health issue. In 2014, it was estimated that 36.9 million people are living with HIV worldwide, including 2.6 million children. Since the advent of combination antiretroviral therapy (cART), in the 1990s, treatment has been so successful that in many parts of the world, HIV has become a chronic condition in which progression to AIDS has become increasingly rare. However, while people with HIV can expect to live a normal life span with cART, lifelong medication is required and cardiovascular, renal, liver, and neurologic diseases are still possible, which continues to prompt research for a cure for HIV...
February 16, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28209198/distribution-and-fate-of-hiv-1-unintegrated-dna-species-a-comprehensive-update
#6
REVIEW
Faysal Bin Hamid, Jinsun Kim, Cha-Gyun Shin
Reverse transcription of viral RNA and the subsequent integration of reverse transcripts are the classical early events of the HIV-1 life-cycle. Simultaneously, abundant unintegrated DNAs (uDNAs), are formed in cells ubiquitously. The uDNAs either undergo recombination or degradation or persist inactively for long periods in the nucleus as future resources. Among them, 2-LTR circles are considered a dead-end for viral spread. Their contribution to the HIV-1 infection is still poorly understood. Nevertheless, the preintegration transcription of the aberrant DNAs and the consequent alterations of cellular factors have already been reported...
February 16, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28193275/immune-regulator-abin1-suppresses-hiv-1-transcription-by-negatively-regulating-the-ubiquitination-of-tat
#7
Shiyou Chen, Xiaodan Yang, Weijia Cheng, Yuhong Ma, Yafang Shang, Liu Cao, Shuliang Chen, Yu Chen, Min Wang, Deyin Guo
BACKGROUND: A20-binding inhibitor of NF-κB activation (ABIN1), an important immune regulator, was previously shown to be involved in HIV-1 replication. However, the reported studies done with overexpressed ABIN1 provided controversial results. RESULTS: Here we identified ABIN1 as a suppressor of HIV-1 transcription since transient knockdown of ABIN1 led to increased HIV-1 replication both in transformed Jurkat T cell line and in primary human CD4+ T lymphocytes...
February 13, 2017: Retrovirology
https://www.readbyqxmd.com/read/28188180/a-population-genomics-approach-to-assessing-the-genetic-basis-of-within-host-microevolution-underlying-recurrent-cryptococcal-meningitis-infection
#8
Johanna Rhodes, Mathew A Beale, Mathieu Vanhove, Joseph N Jarvis, Shichina Kannambath, John A Simpson, Anthea Ryan, Graeme Meintjes, Thomas S Harrison, Matthew C Fisher, Tihana Bicanic
Recurrence of meningitis due to Cryptococcus neoformans after treatment causes substantial mortality in HIV/AIDS patients across sub-Saharan Africa. In order to determine whether recurrence occurred due to relapse of the original infecting isolate or reinfection with a different isolate weeks or months after initial treatment, we used whole-genome sequencing to assess the genetic basis of infection in 17 HIV-infected individuals with recurrent cryptococcal meningitis. Comparisons revealed a clonal relationship for 15 pairs of isolates recovered before and after recurrence showing relapse of the original infection...
February 10, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28187688/identification-of-a-novel-hiv-type-1-recombinant-form-crf01_ae-crf07_bc-in-men-who-have-sex-with-men-in-zhejiang-china
#9
Yufan Xu, Xiaorong Peng, Tiansheng Xie, Xiangyun Lu, Nanping Wu
The prevalence of HIV-1 is increasing rapidly among the population of men who have sex with men (MSM) in China. Here, we report a novel HIV type 1 recombinant form consisting of CRF01_AE and CRF07_BC detected in a male patient through homosexual behavior. A phylogenic analysis revealed that this unique recombinant form (URF) exhibits a complex genomic structure with three CRF07_BC regions inserted into the CRF01_AE backbone. Recently, several second-generation recombinant forms (e.g., CRF01_AE/CRF07_BC) have been identified among MSM in China...
February 10, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28187438/tat-is-a-multifunctional-viral-protein-that-modulates-cellular-gene-expression-and-functions
#10
REVIEW
Evan Clark, Brenda Nava, Massimo Caputi
The human immunodeficiency virus type I (HIV-1) has developed several strategies to condition the host environment to promote viral replication and spread. Viral proteins have evolved to perform multiple functions, aiding in the replication of the viral genome and modulating the cellular response to the infection. Tat is a small, versatile, viral protein that controls transcription of the HIV genome, regulates cellular gene expression and generates a permissive environment for viral replication by altering the immune response and facilitating viral spread to multiple tissues...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185138/the-fourth-central-polypurine-tract-guides-the-synthesis-of-prototype-foamy-virus-plus-strand-dna
#11
Dongxue Chen, Jing Song, Yan Sun, Zhi Li, Didi Wen, Qingmei Liu, Wanhong Liu, Xiaohua He
Foamy virus (FV) is a nonpathogenic retrovirus that has the potential to serve as a gene therapy vector. In retroviral replication, the central polypurine tract (cPPT) is used as a primer to synthesize plus-strand DNA. The cPPT is subsequently degraded to produce a single-stranded gap in the double-stranded viral DNA molecule. In the prototype foamy virus (PFV), four cPPT-like motifs have been previously identified, in which there is a gap with uncertain terminals. In this study, we determined the length of the PFV gap varying from 144 to 731 bp...
February 9, 2017: Virus Genes
https://www.readbyqxmd.com/read/28178277/paucity-of-intact-non-induced-provirus-with-early-long-term-antiretroviral-therapy-of-perinatal-hiv-infection
#12
Kaitlin Rainwater-Lovett, Carrie Ziemniak, Douglas Watson, Katherine Luzuriaga, George Siberry, Ann Petru, YaHui Chen, Priyanka Uprety, Margaret McManus, Ya-Chi Ho, Susanna L Lamers, Deborah Persaud
The latent reservoir is a major barrier to HIV eradication. Reservoir size is emerging as an important biomarker to assess the likelihood of HIV remission in the absence of antiretroviral therapy (ART) and may be reduced by earlier initiation of ART that restricts HIV spread into CD4+ T cells. Reservoir size is traditionally measured with a quantitative viral outgrowth assay (QVOA) that induces replication-competent HIV production through in vitro stimulation of resting CD4+ T cells. However, the recent identification of replication-intact, non-induced proviral genomes (NIPG) suggests the QVOA significantly underestimates (by 62-fold) latent reservoir size in chronically-infected adults...
2017: PloS One
https://www.readbyqxmd.com/read/28178146/pairwise-diversity-and-tmrca-as-potential-markers-for-hiv-infection-recency
#13
Sikhulile Moyo, Eduan Wilkinson, Alain Vandormael, Rui Wang, Jia Weng, Kenanao P Kotokwe, Simani Gaseitsiwe, Rosemary Musonda, Joseph Makhema, Max Essex, Susan Engelbrecht, Tulio de Oliveira, Vladimir Novitsky
Intrahost human immunodeficiency virus (HIV)-1 diversity increases linearly over time. We assessed the extent to which mean pairwise distances and the time to the most recent common ancestor (tMRCA) inferred from intrahost HIV-1C env sequences were associated with the estimated time of HIV infection. Data from a primary HIV-1C infection study in Botswana were used for this analysis (N = 42). A total of 2540 HIV-1C env gp120 variable loop region 1 to conserved region 5 (V1C5) of the HIV-1 envelope gp120 viral sequences were generated by single genome amplification and sequencing, with an average of 61 viral sequences per participant and 11 sequences per time point per participant...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28176813/a-combinational-crispr-cas9-gene-editing-approach-can-halt-hiv-replication-and-prevent-viral-escape
#14
Robert Jan Lebbink, Dorien C M de Jong, Femke Wolters, Elisabeth M Kruse, Petra M van Ham, Emmanuel J H J Wiertz, Monique Nijhuis
HIV presents one of the highest evolutionary rates ever detected and combination antiretroviral therapy is needed to overcome the plasticity of the virus population and control viral replication. Conventional treatments lack the ability to clear the latent reservoir, which remains the major obstacle towards a cure. Novel strategies, such as CRISPR/Cas9 gRNA-based genome-editing, can permanently disrupt the HIV genome. However, HIV genome-editing may accelerate viral escape, questioning the feasibility of the approach...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28154793/predicting-overall-vaccine-efficacy-in-a-new-setting-by-re-calibrating-baseline-covariate-and-intermediate-response-endpoint-effect-modifiers-of-type-specific-vaccine-efficacy
#15
Peter B Gilbert, Ying Huang
We develop a transport formula for predicting overall cumulative vaccine efficacy through time t (VE(t)) to prevent clinically significant infection with a genetically diverse pathogen (e.g., HIV infection) in a new setting for which a Phase III preventive vaccine efficacy trial that would directly estimate VE(t) has not yet been conducted. The formula integrates data from (1) a previous Phase III trial, (2) a Phase I/II immune response biomarker endpoint trial in the new setting where a follow-up Phase III trial is planned, (3) epidemiological data on background HIV infection incidence in the new setting; and (4) genomic epidemiological data on HIV sequence distributions in the previous and new settings...
December 2016: Epidemiologic Methods
https://www.readbyqxmd.com/read/28152379/selective-transduction-of-astrocytic-and-neuronal-cns-subpopulations-by-lentiviral-vectors-pseudotyped-with-chikungunya-virus-envelope
#16
Ioanna Eleftheriadou, Michael Dieringer, Xuan Ying Poh, Julia Sanchez-Garrido, Yunan Gao, Argyro Sgourou, Laura E Simmons, Nicholas D Mazarakis
Lentiviral vectors are gene delivery vehicles that integrate into the host genome of dividing and non-dividing mammalian cells facilitating long-term transgene expression. Lentiviral vector versatility is greatly increased by incorporating heterologous viral envelope proteins onto the vector particles instead of the native envelope, conferring on these pseudotyped vectors a modified tropism and host range specificity. We investigated the pseudotyping efficiency of HIV-1 based lentiviral vectors with alphaviral envelope proteins from the Chikungunya Virus (CHIKV-G) and Sindbis Virus (SINV-G)...
January 23, 2017: Biomaterials
https://www.readbyqxmd.com/read/28148802/recombinant-isfahan-virus-and-vesicular-stomatitis-virus-vaccine-vectors-provide-durable-multivalent-single-dose-protection-against-lethal-alphavirus-challenge
#17
Farooq Nasar, Demetrius Matassov, Robert L Seymour, Theresa Latham, Rodion V Gorchakov, Rebecca M Nowak, Grace Leal, Stefan Hamm, John H Eldridge, Robert B Tesh, David K Clarke, Scott C Weaver
: The demonstrated clinical efficacy of a recombinant vesicular stomatitis virus (rVSV) vaccine vector has stimulated the investigation of additional serologically distinct Vesiculovirus vectors as therapeutic and/or prophylactic vaccine vectors to combat emerging viral diseases. Amongst these viral threats are encephalitic alphaviruses, Venezuelan and eastern equine encephalitic viruses (VEEV, EEEV), which have demonstrated potential for natural disease outbreaks, yet no licensed vaccines are available in the event of an epidemic...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28148784/different-expression-of-interferon-stimulated-genes-in-response-to-hiv-1-infection-in-dendritic-cells-according-to-their-maturation-state
#18
Esther Calonge, Mercedes Bermejo, Francisco Diez-Fuertes, Isabelle Mangeot, Nuria Gonzalez, Mayte Coiras, Laura Jimenez Tormo, Javier García-Perez, Nathalie Dereuddre-Bosquet, Roger Le Grand, José Alcamí
: Dendritic cells (DCs) are professional antigen presenting cells whose functions are dependent on their degree of differentiation. In their immature state, DCs, capture pathogens and migrate to the lymph nodes. During this process DCs become resident mature cells specialized in antigen presentation. DCs are characterized by a highly limiting environment to HIV-1 replication due to the expression of restriction factors as SAMHD1 and APOBEC3G. However, uninfected DCs capture and transfer viral particles to CD4 lymphocytes through a trans-enhancement mechanism in which chemokines are involved...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28141970/a-large-community-outbreak-of-legionnaires-disease-associated-with-a-cooling-tower-in-new-york-city-2015
#19
Don Weiss, Christopher Boyd, Jennifer L Rakeman, Sharon K Greene, Robert Fitzhenry, Trevor McProud, Kimberlee Musser, Li Huang, John Kornblum, Elizabeth J Nazarian, Annie D Fine, Sarah L Braunstein, Daniel Kass, Keren Landman, Pascal Lapierre, Scott Hughes, Anthony Tran, Jill Taylor, Deborah Baker, Lucretia Jones, Laura Kornstein, Boning Liu, Rodolfo Perez, David E Lucero, Eric Peterson, Isaac Benowitz, Kristen F Lee, Stephanie Ngai, Mitch Stripling, Jay K Varma
OBJECTIVES: Infections caused by Legionella are the leading cause of waterborne disease outbreaks in the United States. We investigated a large outbreak of Legionnaires' disease in New York City in summer 2015 to characterize patients, risk factors for mortality, and environmental exposures. METHODS: We defined cases as patients with pneumonia and laboratory evidence of Legionella infection from July 2 through August 3, 2015, and with a history of residing in or visiting 1 of several South Bronx neighborhoods of New York City...
January 1, 2017: Public Health Reports
https://www.readbyqxmd.com/read/28141781/low-dose-hydrocortisone-has-acute-enhancing-effects-on-verbal-learning-in-hiv-infected-men
#20
Leah H Rubin, K Luan Phan, Sheila M Keating, Kathleen M Weber, Pauline M Maki
OBJECTIVE: Glucocorticoids are released in response to stress and alter cognition and brain function through both rapid, nongenomic and slow, genomic mechanisms. Administration of glucocorticoids in the form of hydrocortisone enhances aspects of learning and memory in individuals with PTSD, but impairs these abilities in healthy individuals. We examine the time-dependent effects of glucocorticoids on cognition in HIV-infected men. METHODS: In a double-blind, placebo-controlled, cross-over study, we examined the time-dependent effects of a single low dose of hydrocortisone (10mg; LDH) on cognition in 45 HIV-infected men...
January 30, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
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