Retrovirology最新文献

筛选
英文 中文
Reduced and highly diverse peripheral HIV-1 reservoir in virally suppressed patients infected with non-B HIV-1 strains in Uganda. 乌干达感染非 B 型 HIV-1 株的病毒抑制患者外周 HIV-1 病毒库减少且高度多样化。
IF 3.3 3区 医学
Retrovirology Pub Date : 2022-01-15 DOI: 10.1186/s12977-022-00587-3
Samira Joussef-Piña, Immaculate Nankya, Sophie Nalukwago, Joy Baseke, Sandra Rwambuya, Dane Winner, Fred Kyeyune, Keith Chervenak, Bonnie Thiel, Robert Asaad, Curtis Dobrowolski, Benjamin Luttge, Blair Lawley, Cissy M Kityo, W Henry Boom, Jonathan Karn, Miguel E Quiñones-Mateu
{"title":"Reduced and highly diverse peripheral HIV-1 reservoir in virally suppressed patients infected with non-B HIV-1 strains in Uganda.","authors":"Samira Joussef-Piña, Immaculate Nankya, Sophie Nalukwago, Joy Baseke, Sandra Rwambuya, Dane Winner, Fred Kyeyune, Keith Chervenak, Bonnie Thiel, Robert Asaad, Curtis Dobrowolski, Benjamin Luttge, Blair Lawley, Cissy M Kityo, W Henry Boom, Jonathan Karn, Miguel E Quiñones-Mateu","doi":"10.1186/s12977-022-00587-3","DOIUrl":"10.1186/s12977-022-00587-3","url":null,"abstract":"<p><strong>Background: </strong>Our understanding of the peripheral human immunodeficiency virus type 1 (HIV-1) reservoir is strongly biased towards subtype B HIV-1 strains, with only limited information available from patients infected with non-B HIV-1 subtypes, which are the predominant viruses seen in low- and middle-income countries (LMIC) in Africa and Asia.</p><p><strong>Results: </strong>In this study, blood samples were obtained from well-suppressed ART-experienced HIV-1 patients monitored in Uganda (n = 62) or the U.S. (n = 50), with plasma HIV-1 loads < 50 copies/ml and CD4<sup>+</sup> T-cell counts > 300 cells/ml. The peripheral HIV-1 reservoir, i.e., cell-associated HIV-1 RNA and proviral DNA, was characterized using our novel deep sequencing-based EDITS assay. Ugandan patients were slightly younger (median age 43 vs 49 years) and had slightly lower CD4<sup>+</sup> counts (508 vs 772 cells/ml) than U.S. individuals. All Ugandan patients were infected with non-B HIV-1 subtypes (31% A1, 64% D, or 5% C), while all U.S. individuals were infected with subtype B viruses. Unexpectedly, we observed a significantly larger peripheral inducible HIV-1 reservoir in U.S. patients compared to Ugandan individuals (48 vs. 11 cell equivalents/million cells, p < 0.0001). This divergence in reservoir size was verified measuring proviral DNA (206 vs. 88 cell equivalents/million cells, p < 0.0001). However, the peripheral HIV-1 reservoir was more diverse in Ugandan than in U.S. individuals (8.6 vs. 4.7 p-distance, p < 0.0001).</p><p><strong>Conclusions: </strong>The smaller, but more diverse, peripheral HIV-1 reservoir in Ugandan patients might be associated with viral (e.g., non-B subtype with higher cytopathicity) and/or host (e.g., higher incidence of co-infections or co-morbidities leading to less clonal expansion) factors. This highlights the need to understand reservoir dynamics in diverse populations as part of ongoing efforts to find a functional cure for HIV-1 infection in LMICs.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"19 1","pages":"1"},"PeriodicalIF":3.3,"publicationDate":"2022-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9333113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rotten to the core: antivirals targeting the HIV-1 capsid core. 核心腐烂:针对HIV-1衣壳核心的抗病毒药物。
IF 3.3 3区 医学
Retrovirology Pub Date : 2021-12-22 DOI: 10.1186/s12977-021-00583-z
William M McFadden, Alexa A Snyder, Karen A Kirby, Philip R Tedbury, Monika Raj, Zhengqiang Wang, Stefan G Sarafianos
{"title":"Rotten to the core: antivirals targeting the HIV-1 capsid core.","authors":"William M McFadden,&nbsp;Alexa A Snyder,&nbsp;Karen A Kirby,&nbsp;Philip R Tedbury,&nbsp;Monika Raj,&nbsp;Zhengqiang Wang,&nbsp;Stefan G Sarafianos","doi":"10.1186/s12977-021-00583-z","DOIUrl":"https://doi.org/10.1186/s12977-021-00583-z","url":null,"abstract":"<p><p>The capsid core of HIV-1 is a large macromolecular assembly that surrounds the viral genome and is an essential component of the infectious virus. In addition to its multiple roles throughout the viral life cycle, the capsid interacts with multiple host factors. Owing to its indispensable nature, the HIV-1 capsid has been the target of numerous antiretrovirals, though most capsid-targeting molecules have not had clinical success until recently. Lenacapavir, a long-acting drug that targets the HIV-1 capsid, is currently undergoing phase 2/3 clinical trials, making it the most successful capsid inhibitor to-date. In this review, we detail the role of the HIV-1 capsid protein in the virus life cycle, categorize antiviral compounds based on their targeting of five sites within the HIV-1 capsid, and discuss their molecular interactions and mechanisms of action. The diverse range of inhibition mechanisms provides insight into possible new strategies for designing novel HIV-1 drugs and furthers our understanding of HIV-1 biology.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"18 1","pages":"41"},"PeriodicalIF":3.3,"publicationDate":"2021-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9999643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 18
HIV-1 integrase binding to genomic RNA 5'-UTR induces local structural changes in vitro and in virio. 结合基因组RNA 5'-UTR的HIV-1整合酶在体外和体内诱导局部结构变化。
IF 3.3 3区 医学
Retrovirology Pub Date : 2021-11-22 DOI: 10.1186/s12977-021-00582-0
Shuohui Liu, Pratibha C Koneru, Wen Li, Chathuri Pathirage, Alan N Engelman, Mamuka Kvaratskhelia, Karin Musier-Forsyth
{"title":"HIV-1 integrase binding to genomic RNA 5'-UTR induces local structural changes in vitro and in virio.","authors":"Shuohui Liu,&nbsp;Pratibha C Koneru,&nbsp;Wen Li,&nbsp;Chathuri Pathirage,&nbsp;Alan N Engelman,&nbsp;Mamuka Kvaratskhelia,&nbsp;Karin Musier-Forsyth","doi":"10.1186/s12977-021-00582-0","DOIUrl":"https://doi.org/10.1186/s12977-021-00582-0","url":null,"abstract":"<p><strong>Background: </strong>During HIV-1 maturation, Gag and Gag-Pol polyproteins are proteolytically cleaved and the capsid protein polymerizes to form the honeycomb capsid lattice. HIV-1 integrase (IN) binds the viral genomic RNA (gRNA) and impairment of IN-gRNA binding leads to mis-localization of the nucleocapsid protein (NC)-condensed viral ribonucleoprotein complex outside the capsid core. IN and NC were previously demonstrated to bind to the gRNA in an orthogonal manner in virio; however, the effect of IN binding alone or simultaneous binding of both proteins on gRNA structure is not yet well understood.</p><p><strong>Results: </strong>Using crosslinking-coupled selective 2'-hydroxyl acylation analyzed by primer extension (XL-SHAPE), we characterized the interaction of IN and NC with the HIV-1 gRNA 5'-untranslated region (5'-UTR). NC preferentially bound to the packaging signal (Psi) and a UG-rich region in U5, irrespective of the presence of IN. IN alone also bound to Psi but pre-incubation with NC largely abolished this interaction. In contrast, IN specifically bound to and affected the nucleotide (nt) dynamics of the apical loop of the transactivation response element (TAR) and the polyA hairpin even in the presence of NC. SHAPE probing of the 5'-UTR RNA in virions produced from allosteric IN inhibitor (ALLINI)-treated cells revealed that while the global secondary structure of the 5'-UTR remained unaltered, the inhibitor treatment induced local reactivity differences, including changes in the apical loop of TAR that are consistent with the in vitro results.</p><p><strong>Conclusions: </strong>Overall, the binding interactions of NC and IN with the 5'-UTR are largely orthogonal in vitro. This study, together with previous probing experiments, suggests that IN and NC binding in vitro and in virio lead to only local structural changes in the regions of the 5'-UTR probed here. Accordingly, disruption of IN-gRNA binding by ALLINI treatment results in local rather than global secondary structure changes of the 5'-UTR in eccentric virus particles.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"18 1","pages":"37"},"PeriodicalIF":3.3,"publicationDate":"2021-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10449602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Diverse antiviral IgG effector activities are predicted by unique biophysical antibody features. 独特的生物物理抗体特征预测了多种抗病毒IgG效应物的活性。
IF 3.3 3区 医学
Retrovirology Pub Date : 2021-10-30 DOI: 10.1186/s12977-021-00579-9
Hao D Cheng, Karen G Dowell, Chris Bailey-Kellogg, Brittany A Goods, J Christopher Love, Guido Ferrari, Galit Alter, Johannes Gach, Donald N Forthal, George K Lewis, Kelli Greene, Hongmei Gao, David C Montefiori, Margaret E Ackerman
{"title":"Diverse antiviral IgG effector activities are predicted by unique biophysical antibody features.","authors":"Hao D Cheng,&nbsp;Karen G Dowell,&nbsp;Chris Bailey-Kellogg,&nbsp;Brittany A Goods,&nbsp;J Christopher Love,&nbsp;Guido Ferrari,&nbsp;Galit Alter,&nbsp;Johannes Gach,&nbsp;Donald N Forthal,&nbsp;George K Lewis,&nbsp;Kelli Greene,&nbsp;Hongmei Gao,&nbsp;David C Montefiori,&nbsp;Margaret E Ackerman","doi":"10.1186/s12977-021-00579-9","DOIUrl":"https://doi.org/10.1186/s12977-021-00579-9","url":null,"abstract":"<p><strong>Background: </strong>The critical role of antibody Fc-mediated effector functions in immune defense has been widely reported in various viral infections. These effector functions confer cellular responses through engagement with innate immune cells. The precise mechanism(s) by which immunoglobulin G (IgG) Fc domain and cognate receptors may afford protection are poorly understood, however, in the context of HIV/SHIV infections. Many different in vitro assays have been developed and utilized to measure effector functions, but the extent to which these assays capture distinct antibody activities has not been fully elucidated.</p><p><strong>Results: </strong>In this study, six Fc-mediated effector function assays and two biophysical antibody profiling assays were performed on a common set of samples from HIV-1 infected and vaccinated subjects. Biophysical antibody profiles supported robust prediction of diverse IgG effector functions across distinct Fc-mediated effector function assays. While a number of assays showed correlated activities, supervised machine learning models indicated unique antibody features as primary contributing factors to the associated effector functions. Additional experiments established the mechanistic relevance of relationships discovered using this unbiased approach.</p><p><strong>Conclusions: </strong>In sum, this study provides better resolution on the diversity and complexity of effector function assays, offering a clearer perspective into this family of antibody mechanisms of action to inform future HIV-1 treatment and vaccination strategies.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"18 1","pages":"35"},"PeriodicalIF":3.3,"publicationDate":"2021-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10871265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Altered Env conformational dynamics as a mechanism of resistance to peptide-triazole HIV-1 inactivators. 改变的环境构象动力学作为对肽-三唑类HIV-1灭活剂的抗性机制。
IF 3.3 3区 医学
Retrovirology Pub Date : 2021-10-09 DOI: 10.1186/s12977-021-00575-z
Shiyu Zhang, Andrew P Holmes, Alexej Dick, Adel A Rashad, Lucía Enríquez Rodríguez, Gabriela A Canziani, Michael J Root, Irwin M Chaiken
{"title":"Altered Env conformational dynamics as a mechanism of resistance to peptide-triazole HIV-1 inactivators.","authors":"Shiyu Zhang,&nbsp;Andrew P Holmes,&nbsp;Alexej Dick,&nbsp;Adel A Rashad,&nbsp;Lucía Enríquez Rodríguez,&nbsp;Gabriela A Canziani,&nbsp;Michael J Root,&nbsp;Irwin M Chaiken","doi":"10.1186/s12977-021-00575-z","DOIUrl":"https://doi.org/10.1186/s12977-021-00575-z","url":null,"abstract":"<p><strong>Background: </strong>We previously developed drug-like peptide triazoles (PTs) that target HIV-1 Envelope (Env) gp120, potently inhibit viral entry, and irreversibly inactivate virions. Here, we investigated potential mechanisms of viral escape from this promising class of HIV-1 entry inhibitors.</p><p><strong>Results: </strong>HIV-1 resistance to cyclic (AAR029b) and linear (KR13) PTs was obtained by dose escalation in viral passaging experiments. High-level resistance for both inhibitors developed slowly (relative to escape from gp41-targeted C-peptide inhibitor C37) by acquiring mutations in gp120 both within (Val255) and distant to (Ser143) the putative PT binding site. The similarity in the resistance profiles for AAR029b and KR13 suggests that the shared IXW pharmacophore provided the primary pressure for HIV-1 escape. In single-round infectivity studies employing recombinant virus, V255I/S143N double escape mutants reduced PT antiviral potency by 150- to 3900-fold. Curiously, the combined mutations had a much smaller impact on PT binding affinity for monomeric gp120 (four to ninefold). This binding disruption was entirely due to the V255I mutation, which generated few steric clashes with PT in molecular docking. However, this minor effect on PT affinity belied large, offsetting changes to association enthalpy and entropy. The escape mutations had negligible effect on CD4 binding and utilization during entry, but significantly altered both binding thermodynamics and inhibitory potency of the conformationally-specific, anti-CD4i antibody 17b. Moreover, the escape mutations substantially decreased gp120 shedding induced by either soluble CD4 or AAR029b.</p><p><strong>Conclusions: </strong>Together, the data suggest that the escape mutations significantly modified the energetic landscape of Env's prefusogenic state, altering conformational dynamics to hinder PT-induced irreversible inactivation of Env. This work therein reveals a unique mode of virus escape for HIV-1, namely, resistance by altering the intrinsic conformational dynamics of the Env trimer.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"18 1","pages":"31"},"PeriodicalIF":3.3,"publicationDate":"2021-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10169211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
A novel Betaretrovirus discovered in cattle with neurological disease and encephalitis 在患有神经系统疾病和脑炎的牛中发现的一种新型β病毒
IF 3.3 3区 医学
Retrovirology Pub Date : 2021-08-31 DOI: 10.21203/rs.3.rs-841479/v1
Melanie M Hierweger, M. Koch, R. Kauer, Z. Bagó, A. Oevermann, G. Bertoni, T. Seuberlich
{"title":"A novel Betaretrovirus discovered in cattle with neurological disease and encephalitis","authors":"Melanie M Hierweger, M. Koch, R. Kauer, Z. Bagó, A. Oevermann, G. Bertoni, T. Seuberlich","doi":"10.21203/rs.3.rs-841479/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-841479/v1","url":null,"abstract":"Background The majority of emerging infectious diseases in humans are of animal origin, and many of them are caused by neuropathogenic viruses. Many cases of neurological disease and encephalitis in livestock remain etiologically unresolved, posing a constant threat to animal and human health. Thus, continuous extension of our knowledge of the repertoire of viruses prone to infect the central nervous system (CNS) is vital for pathogen monitoring and the early detection of emerging viruses. Using high-throughput sequencing (HTS) and bioinformatics, we discovered a new retrovirus, bovine retrovirus CH15 (BoRV CH15), in the CNS of a cow with non-suppurative encephalitis. Phylogenetic analysis revealed the affiliation of BoRV CH15 to the genus Betaretrovirus. Results BoRV CH15 genomes were identified prospectively and retrospectively by PCR, RT-PCR, and HTS, with targeting of viral RNA and proviral DNA, in six additional diseased cows investigated over a period of > 20 years and of different geographical origins. The virus was not found in brain samples from healthy slaughtered control animals (n = 130). We determined the full-length proviral genomes from six of the seven investigated animals and, using in situ hybridization, identified viral RNA in the cytoplasm of cells morphologically compatible with neurons in diseased brains. Conclusions Further screening of brain samples, virus isolation, and infection studies are needed to estimate the significance of these findings and the causative association of BoRV CH15 with neurological disease and encephalitis in cattle. However, with the full-length proviral sequences of BoRV CH15 genomes, we provide the basis for a molecular clone and further in vitro investigation. Graphical Abstract","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41507438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Humanized Mice for Infectious and Neurodegenerative disorders. 用于感染性和神经退行性疾病的人源化小鼠。
IF 2.7 3区 医学
Retrovirology Pub Date : 2021-06-05 DOI: 10.1186/s12977-021-00557-1
Prasanta K Dash, Santhi Gorantla, Larisa Poluektova, Mahmudul Hasan, Emiko Waight, Chen Zhang, Milica Markovic, Benson Edagwa, Jatin Machhi, Katherine E Olson, Xinglong Wang, R Lee Mosley, Bhavesh Kevadiya, Howard E Gendelman
{"title":"Humanized Mice for Infectious and Neurodegenerative disorders.","authors":"Prasanta K Dash, Santhi Gorantla, Larisa Poluektova, Mahmudul Hasan, Emiko Waight, Chen Zhang, Milica Markovic, Benson Edagwa, Jatin Machhi, Katherine E Olson, Xinglong Wang, R Lee Mosley, Bhavesh Kevadiya, Howard E Gendelman","doi":"10.1186/s12977-021-00557-1","DOIUrl":"10.1186/s12977-021-00557-1","url":null,"abstract":"<p><p>Humanized mice model human disease and as such are used commonly for research studies of infectious, degenerative and cancer disorders. Recent models also reflect hematopoiesis, natural immunity, neurobiology, and molecular pathways that influence disease pathobiology. A spectrum of immunodeficient mouse strains permit long-lived human progenitor cell engraftments. The presence of both innate and adaptive immunity enables high levels of human hematolymphoid reconstitution with cell susceptibility to a broad range of microbial infections. These mice also facilitate investigations of human pathobiology, natural disease processes and therapeutic efficacy in a broad spectrum of human disorders. However, a bridge between humans and mice requires a complete understanding of pathogen dose, co-morbidities, disease progression, environment, and genetics which can be mirrored in these mice. These must be considered for understanding of microbial susceptibility, prevention, and disease progression. With known common limitations for access to human tissues, evaluation of metabolic and physiological changes and limitations in large animal numbers, studies in mice prove important in planning human clinical trials. To these ends, this review serves to outline how humanized mice can be used in viral and pharmacologic research emphasizing both current and future studies of viral and neurodegenerative diseases. In all, humanized mouse provides cost-effective, high throughput studies of infection or degeneration in natural pathogen host cells, and the ability to test transmission and eradication of disease.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"18 1","pages":"13"},"PeriodicalIF":2.7,"publicationDate":"2021-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9762126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract withdrawn 摘要已撤回
IF 3.3 3区 医学
Retrovirology Pub Date : 2021-02-01 DOI: 10.1186/1742-4690-2-S1-P92
{"title":"Abstract withdrawn","authors":"","doi":"10.1186/1742-4690-2-S1-P92","DOIUrl":"https://doi.org/10.1186/1742-4690-2-S1-P92","url":null,"abstract":"","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"2 1","pages":"1"},"PeriodicalIF":3.3,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1742-4690-2-S1-P92","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49219284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study. 乌干达HIV-1精英控制者和非控制者中Trim5α和亲环蛋白A基因的变异:一项基于实验室的横断面研究
IF 3.3 3区 医学
Retrovirology Pub Date : 2020-07-06 DOI: 10.1186/s12977-020-00527-z
Sharon Bright Amanya, Brian Nyiro, Francis Waswa, Bonniface Obura, Rebecca Nakaziba, Eva Nabulime, Ashaba Fred Katabazi, Rose Nabatanzi, Alice Bayiyana, Gerald Mboowa, Alex Kayongo, Misaki Wayengera, Obondo J Sande
{"title":"Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study.","authors":"Sharon Bright Amanya,&nbsp;Brian Nyiro,&nbsp;Francis Waswa,&nbsp;Bonniface Obura,&nbsp;Rebecca Nakaziba,&nbsp;Eva Nabulime,&nbsp;Ashaba Fred Katabazi,&nbsp;Rose Nabatanzi,&nbsp;Alice Bayiyana,&nbsp;Gerald Mboowa,&nbsp;Alex Kayongo,&nbsp;Misaki Wayengera,&nbsp;Obondo J Sande","doi":"10.1186/s12977-020-00527-z","DOIUrl":"https://doi.org/10.1186/s12977-020-00527-z","url":null,"abstract":"<p><strong>Background: </strong>Tripartite Motif Containing 5 alpha (TRIM5α), a restriction factor produced ubiquitously in cells and tissues of the body plays an important role in the immune response against HIV. TRIM5α targets the HIV capsid for proteosomal destruction. Cyclophilin A, an intracellular protein has also been reported to influence HIV infectivity in a cell-specific manner. Accordingly, variations in TRIM5α and Cyclophilin A genes have been documented to influence HIV-1 disease progression. However, these variations have not been documented among Elite controllers in Uganda and whether they play a role in viral suppression remains largely undocumented. Our study focused on identifying the variations in TRIM5α and Cyclophilin A genes among HIV-1 Elite controllers and non-controllers in Uganda.</p><p><strong>Results: </strong>From the sequence analysis, the rs10838525 G > A mutation in exon 2 of TRIM5α was only found among elite controllers (30%) while the rs3824949 in the 5'UTR was seen among 25% of the non-controllers. In the Cyclophilin A promoter, rs6850 was seen among 62.5% of the non-controllers and only among 10% elite controllers. Furthermore, rs17860048 in the Cyclophillin A promoter was predominantly seen among elite controllers (30%) and 12.5% non-controllers. From gene expression analysis, we noted that the respective genes were generally elevated among elite controllers, however, this difference was not statistically significant (TRIM5α p = 0.6095; Cyclophilin A p = 0.6389).</p><p><strong>Conclusion: </strong>Variations in TRIM5α and Cyclophillin A promoter may influence HIV viral suppression. The rs10838525 SNP in TRIM5α may contribute to viral suppression among HIV-1 elite controllers. The rs6850 in the cyclophillin A gene may be responsible for HIV-1 rapid progression among HIV-1 non-controllers. These SNPs should be investigated mechanistically to determine their precise role in HIV-1 viral suppression.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":"17 1","pages":"19"},"PeriodicalIF":3.3,"publicationDate":"2020-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12977-020-00527-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10776777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry HIV-1包膜糖蛋白n端七肽重复区Glu560突变有助于对病毒进入肽抑制剂的抗性
IF 3.3 3区 医学
Retrovirology Pub Date : 2019-12-01 DOI: 10.1186/s12977-019-0496-8
Chen Yuan, Jiaye Wang, Hai-Jiao Zhao, Yan Li, Di Li, H. Ling, Zhuang Min
{"title":"Mutations of Glu560 within HIV-1 Envelope Glycoprotein N-terminal heptad repeat region contribute to resistance to peptide inhibitors of virus entry","authors":"Chen Yuan, Jiaye Wang, Hai-Jiao Zhao, Yan Li, Di Li, H. Ling, Zhuang Min","doi":"10.1186/s12977-019-0496-8","DOIUrl":"https://doi.org/10.1186/s12977-019-0496-8","url":null,"abstract":"","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12977-019-0496-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43545509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信