Retrovirology最新文献

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"title":"Immunovirological markers in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)","authors":"Yoshimi Enose-Akahata, S. Jacobson","doi":"10.1186/s12977-019-0499-5","DOIUrl":"https://doi.org/10.1186/s12977-019-0499-5","url":null,"abstract":"","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2019-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12977-019-0499-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45298437","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}

{"title":"Restriction factors in human retrovirus infections and the unprecedented case of CIITA as link of intrinsic and adaptive immunity against HTLV-1","authors":"G. Forlani, Mariam Shallak, Elise Ramia, A. Tedeschi, R. Accolla","doi":"10.1186/s12977-019-0498-6","DOIUrl":"https://doi.org/10.1186/s12977-019-0498-6","url":null,"abstract":"","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2019-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12977-019-0498-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46007024","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}

{"title":"Deltaretroviruses have circulated since at least the Paleogene and infected a broad range of mammalian species","authors":"T. Hron, D. Elleder, R. Gifford","doi":"10.1186/s12977-019-0495-9","DOIUrl":"https://doi.org/10.1186/s12977-019-0495-9","url":null,"abstract":"","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2019-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12977-019-0495-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45538998","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}