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Quasispecies

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https://www.readbyqxmd.com/read/28327559/quasispecies-of-hepatitis-c-virus-participate-in-cell-specific-infectivity
#1
Takasuke Fukuhara, Satomi Yamamoto, Chikako Ono, Shota Nakamura, Daisuke Motooka, Hiroyuki Mori, Takeshi Kurihara, Asuka Sato, Tomokazu Tamura, Takashi Motomura, Toru Okamoto, Michio Imamura, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Kazuaki Chayama, Yoshiharu Matsuura
It is well documented that a variety of viral quasispecies are found in the patients with chronic infection of hepatitis C virus (HCV). However, the significance of quasispecies in the specific infectivity to individual cell types remains unknown. In the present study, we analyzed the role of quasispecies of the genotype 2a clone, JFH1 (HCVcc), in specific infectivity to the hepatic cell lines, Huh7.5.1 and Hep3B. HCV RNA was electroporated into Huh7.5.1 cells and Hep3B/miR-122 cells expressing miR-122 at a high level...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325923/clinical-features-and-viral-quasispecies-characteristics-associated-with-infection-by-the-hepatitis-b-virus-g145r-immune-escape-mutant
#2
Yuan Xue, Ming-Jie Wang, Zhi-Tao Yang, De-Min Yu, Yue Han, Dao Huang, Dong-Hua Zhang, Xin-Xin Zhang
Coexistence of the hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) is an uncommon phenomenon, and the underlying mechanisms remain largely unknown. Amino-acid (aa) substitution from glycine to arginine at aa 145 (G145R), in the major hydrophilic region, has been reported in patients with HBsAg and anti-HBs coexistence. However, there is limited knowledge about the clinical features and viral quasispecies characteristics associated with G145R mutant hepatitis B virus (HBV) infection...
March 22, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28320417/impaired-human-immunodeficiency-virus-type-1-replicative-fitness-in-atypical-viremic-non-progressor-individuals
#3
Jan Weber, Richard M Gibson, Lenka Sácká, Dmytro Strunin, Jan Hodek, Jitka Weberová, Marcela Pávová, David J Alouani, Robert Asaad, Benigno Rodriguez, Michael M Lederman, Miguel E Quiñones-Mateu
BACKGROUND: Progression rates from initial HIV-1 infection to advanced AIDS vary significantly among infected individuals. A distinct subgroup of HIV-1-infected individuals-termed viremic non-progressors (VNP) or controllers-do not seem to progress to AIDS, maintaining high CD4(+) T cell counts despite high levels of viremia for many years. Several studies have evaluated multiple host factors, including immune activation, trying to elucidate the atypical HIV-1 disease progression in these patients; however, limited work has been done to characterize viral factors in viremic controllers...
March 20, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28303969/hbv-quasispecies-composition-in-lamivudine-failed-chronic-hepatitis-b-patients-and-its-influence-on-virological-response-to-tenofovir-based-rescue-therapy
#4
Priyanka Banerjee, Abhijit Chakraborty, Rajiv Kumar Mondal, Mousumi Khatun, Somenath Datta, Kausik Das, Pratap Pandit, Souvik Mukherjee, Soma Banerjee, Saurabh Ghosh, Saikat Chakrabarti, Abhijit Chowdhury, Simanti Datta
The present study sought to evaluate the structure of HBV quasispecies in Lamivudine (LMV)-failed chronic hepatitis B (CHB) patients and its impact in defining the subsequent virological responses to Tenofovir (TDF)-based rescue-therapy. By analyzing HBV clones encompassing reverse transcriptase (RT) and surface (S) region from LMV-failed and treatment-naïve CHB patients, we identified 5 classical and 12 novel substitutions in HBV/RT and 9 substitutions in immune-epitopes of HBV/S that were significantly associated with LMV failure...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28301421/persistence-of-hiv-drug-resistance-among-south-african-children-given-nevirapine-to-prevent-mother-to-child-transmission
#5
Ruth Kanthula, Theresa Rossouw, Ute D Feucht, Gisela Van Dyk, Ingrid A Beck, Rachel Silverman, Scott Olson, Christen Salyer, Sharon Cassol, Lisa M Frenkel
OBJECTIVES: We set out to examine the prevalence and persistence of mutations conferring high-level nonnucleoside-reverse-transcriptase (NNRTI)-resistance in a cohort of HIV-infected children who had failed prophylaxis to prevent mother-to-child-transmission (PMTCT). DESIGN: A prospective observational cohort study at the Pediatric HIV Clinic at Kalafong Provincial Tertiary Hospital in Pretoria, South Africa. METHODS: Children referred for initiation of ART were enrolled from July 2010 through February 2013...
March 15, 2017: AIDS
https://www.readbyqxmd.com/read/28299895/deep-sequencing-and-variant-analysis-of-an-italian-pathogenic-field-strain-of-equine-infectious-anaemia-virus
#6
K Cappelli, R F Cook, V Stefanetti, F Passamonti, G L Autorino, M T Scicluna, M Coletti, A Verini Supplizi, S Capomaccio
Equine infectious anaemia virus (EIAV) is a lentivirus with an almost worldwide distribution that causes persistent infections in equids. Technical limitations have restricted genetic analysis of EIAV field isolates predominantly to gag sequences resulting in very little published information concerning the extent of inter-strain variation in pol, env and the three ancillary open reading frames (ORFs). Here, we describe the use of long-range PCR in conjunction with next-generation sequencing (NGS) for rapid molecular characterization of all viral ORFs and known transcription factor binding motifs within the long terminal repeat of two EIAV isolates from the 2006 Italian outbreak...
March 15, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/28285909/interferon-i-the-pi%C3%A3-ce-de-r%C3%A3-sistance-of-hiv-1-transmission
#7
Damien C Tully, Daniel T Claiborne, Todd M Allen
Despite the extensive viral quasispecies that develops in an individual during the course of HIV-1 infection, transmission is typically established by a single donor viral variant. Recent studies now provide insight into the phenotypic properties influencing this selection process at transmission, including the contribution of resistance to type I interferons.
March 9, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28284234/humoral-immune-system-targets-clonotypic-antibody-associated-hepatitis-c-virus
#8
Amruta S Naik, Brendan A Palmer, Orla Crosbie, Elizabeth Kenny-Walsh, Liam J Fanning
Hypervariable region 1 (HVR1) is one of the potential neutralization domains in the E2 glycoprotein of hepatitis C virus (HCV). Point mutations of the HVR1 can lead to humoral immune escape in HCV-infected patients. In this study, we segregated the chronically infected viraemic sera from HCV-infected patients into populations of antibody-free virus and antibody-associated virus (AAV) and mapped potential epitopes within the E1E2 gene junction of AAV sequences (residues 364-430). Furthermore, we generated HCV pseudoparticles (HCVpp) derived from AAV sequences to assess their infectivity...
February 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28275194/internal-disequilibria-and-phenotypic-diversification-during-replication-of-hepatitis-c-virus-in-a-non-coevolving-cellular-environment
#9
Elena Moreno, Isabel Gallego, Josep Gregori, Adriana Lucía-Sanz, María Eugenia Soria, Victoria Castro, Nathan M Beach, Susanna C Manrubia, Josep Quer, Juan Ignacio Esteban, Charles M Rice, Jordi Gómez, Pablo Gastaminza, Esteban Domingo, Celia Perales
Viral quasispecies evolution upon long-term virus replication in a non-coevolving cellular environment raises relevant general issues such as the attainment of population equilibrium, compliance with the molecular clock hypothesis or stability of the phenotypic profile. Here we evaluate adaptation, mutant spectrum dynamics, and phenotypic diversification of hepatitis C virus (HCV) in the course of two hundred passages in human hepatoma cells in an experimental design that precluded coevolution of the cells with the virus...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28263814/convergence-of-a-moran-model-to-eigen-s-quasispecies-model
#10
Joseba Dalmau
We prove that a Moran model converges in probability to Eigen's quasispecies model in the infinite population limit. We show further that the invariant probability measure of the Moran model converges to the unique stationary solution of Eigen's quasispecies model.
March 2, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28247269/dynamic-of-csf-and-serum-biomarkers-in-hiv-1-subtype-c-encephalitis-with-cns-genetic-compartmentalization-case-study
#11
Sergio M de Almeida, Indianara Rotta, Clea E Ribeiro, Michelli F Oliveira, Antoine Chaillon, Ana Paula de Pereira, Ana Paula Cunha, Marise Zonta, Joao França Bents, Sonia M Raboni, Davey Smith, Scott Letendre, Ronald J Ellis
Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples...
February 28, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28240183/influenza-a-virus-nucleoprotein-a-highly-conserved-multi-functional-viral-protein-as-a-hot-antiviral-drug-target
#12
Yanmei Hu, Hannah Sneyd, Raphael Dekant, Jun Wang
Prevention and treatment of influenza virus infection is an ongoing unmet medical need. Each year, thousands of deaths and millions of hospitalizations are attributed to influenza virus infection, which poses a tremendous health and economic burden to the society. Aside from the annual influenza season, influenza viruses also lead to occasional influenza pandemics as a result of emerging or re-emerging influenza strains. Influenza viruses are RNA viruses that exist in quasispecies, meaning that they have a very diverse genetic background...
February 24, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28239654/flow-virometric-sorting-and-analysis-of-hiv-quasispecies-from-plasma
#13
Thomas Musich, Jennifer C Jones, Brandon F Keele, Lisa M Miller Jenkins, Thorsten Demberg, Thomas S Uldrick, Robert Yarchoan, Marjorie Robert-Guroff
Flow cytometry is utilized extensively for cellular analysis, but technical limitations have prevented its routine application for characterizing virus. The recent introduction of nanoscale fluorescence-activated cytometric cell sorting now allows analysis of individual virions. Here, we demonstrate staining and sorting of infectious HIV. Fluorescent antibodies specific for cellular molecules found on budding virions were used to label CCR5-tropic Bal HIV and CXCR4-tropic NL4.3 HIV Env-expressing pseudovirions made in THP-1 cells (monocyte/macrophage) and H9 cells (T cells), respectively...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28207488/lessons-learned-from-humoral-responses-of-hiv-patients
#14
Laura E McCoy, Áine McKnight
PURPOSE OF REVIEW: Since 2009 many broadly neutralizing antibodies against HIV have been identified, yet there is still no vaccine capable of inducing such antibodies in humans. This review considers the early observations of HIV sera neutralization in light of more recent studies and highlights areas for future research. RECENT FINDINGS: Large clinical cohort studies using standardized neutralization assays and pseudoviruses derived from primary isolates have shown that 10-30% of HIV infections result in some level of serum neutralization breadth...
February 15, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28205569/heteroaryldihydropyrimidine-hap-and-sulfamoylbenzamide-sba-inhibit-hepatitis-b-virus-replication-by-different-molecular-mechanisms
#15
Zheng Zhou, Taishan Hu, Xue Zhou, Steffen Wildum, Fernando Garcia-Alcalde, Zhiheng Xu, Daitze Wu, Yi Mao, Xiaojun Tian, Yuan Zhou, Fang Shen, Zhisen Zhang, Guozhi Tang, Isabel Najera, Guang Yang, Hong C Shen, John A T Young, Ning Qin
Heteroaryldihydropyrimidine (HAP) and sulfamoylbenzamide (SBA) are promising non-nucleos(t)ide HBV replication inhibitors. HAPs are known to promote core protein mis-assembly, but the molecular mechanism of abnormal assembly is still elusive. Likewise, the assembly status of core protein induced by SBA remains unknown. Here we show that SBA, unlike HAP, does not promote core protein mis-assembly. Interestingly, two reference compounds HAP_R01 and SBA_R01 bind to the same pocket at the dimer-dimer interface in the crystal structures of core protein Y132A hexamer...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197136/characterization-of-the-genomic-diversity-of-norovirus-in-linked-patients-using-a-metagenomic-deep-sequencing-approach
#16
Neda Nasheri, Nicholas Petronella, Jennifer Ronholm, Sabah Bidawid, Nathalie Corneau
Norovirus (NoV) is the leading cause of gastroenteritis worldwide. A robust cell culture system does not exist for NoV and therefore detailed characterization of outbreak and sporadic strains relies on molecular techniques. In this study, we employed a metagenomic approach that uses non-specific amplification followed by next-generation sequencing to whole genome sequence NoV genomes directly from clinical samples obtained from 8 linked patients. Enough sequencing depth was obtained for each sample to use a de novo assembly of near-complete genome sequences...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28181035/complete-genome-sequence-of-a-hepatitis-b-virus-isolate-of-genotype-d2-subtype-adrq-from-brazil
#17
Natália Spitz, Aline S Moreira, Francisco C A Mello, Helena Cristina F Franz, Selma A Gomes, Natalia M Araujo
Hepatitis B virus (HBV) has been classified into 10 distinct serological subtypes of the surface antigen (HBsAg) that can be predicted by sequencing of the corresponding S gene. HBV genotype D usually displays determinants of subtypes ayw2 or ayw3. On the other hand, subtype adrq+ has been found exclusively in association with genotype C. Here, we describe the first HBV genome (isolate BR32) belonging to genotype D with the serological subtype adrq+. This isolate had a genome length of 3,062 nucleotides (nt), and no recombination events were observed in the BR32 genome that could explain the occurrence of the subtype adr in a genotype D isolate...
February 8, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28163093/picornaviral-polymerase-structure-function-and-fidelity-modulation
#18
REVIEW
Olve B Peersen
Like all positive strand RNA viruses, the picornaviruses replicate their genomes using a virally encoded RNA-dependent RNA polymerase enzyme known as 3D(pol). Over the past decade we have made tremendous advances in our understanding of 3D(pol) structure and function, including the discovery of a novel mechanism for closing the active site that allows these viruses to easily fine tune replication fidelity and quasispecies distributions. This review summarizes current knowledge of picornaviral polymerase structure and how the enzyme interacts with RNA and other viral proteins to form stable and processive elongation complexes...
February 2, 2017: Virus Research
https://www.readbyqxmd.com/read/28134353/baseline-quasispecies-selection-and-novel-mutations-contribute-to-emerging-resistance-associated-substitutions-in-hepatitis-c-virus-after-direct-acting-antiviral-treatment
#19
Yugo Kai, Hayato Hikita, Naoki Morishita, Kazuhiro Murai, Tasuku Nakabori, Sadaharu Iio, Hideki Hagiwara, Yasuharu Imai, Shinji Tamura, Syusaku Tsutsui, Masafumi Naito, Meiko Nishiuchi, Yasuteru Kondo, Takanobu Kato, Hiroshi Suemizu, Ryoko Yamada, Tsugiko Oze, Takayuki Yakushijin, Naoki Hiramatsu, Ryotaro Sakamori, Tomohide Tatsumi, Tetsuo Takehara
Resistance-associated substitutions (RASs) in hepatitis C virus (HCV) appear upon failure of treatment with direct-acting antivirals (DAAs). However, their origin has not been clarified in detail. Among 11 HCV genotype 1b patients who experienced virologic failure with asunaprevir (ASV)/daclatasvir (DCV), 10 had major NS5A L31M/V-Y93H variants after treatment. L31M/V-Y93H variants were detected as a minor clone before therapy in 6 patients and were the most closely related to the post-treatment variants by phylogenetic tree analysis in 4 patients...
January 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28103248/effect-of-the-latent-reservoir-on-the-evolution-of-hiv-at-the-within-and-between-host-levels
#20
Hilje M Doekes, Christophe Fraser, Katrina A Lythgoe
The existence of long-lived reservoirs of latently infected CD4+ T cells is the major barrier to curing HIV, and has been extensively studied in this light. However, the effect of these reservoirs on the evolutionary dynamics of the virus has received little attention. Here, we present a within-host quasispecies model that incorporates a long-lived reservoir, which we then nest into an epidemiological model of HIV dynamics. For biologically plausible parameter values, we find that the presence of a latent reservoir can severely delay evolutionary dynamics within a single host, with longer delays associated with larger relative reservoir sizes and/or homeostatic proliferation of cells within the reservoir...
January 2017: PLoS Computational Biology
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