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Karla Kirkegaard, Nicholas J van Buuren, Roberto Mateo
If a freshly minted genome contains a mutation that confers drug resistance, will it be selected in the presence of the drug? Not necessarily. During viral infections, newly synthesized viral genomes occupy the same cells as parent and other progeny genomes. If the antiviral target is chosen so that the drug-resistant progeny's growth is dominantly inhibited by the drug-susceptible members of its intracellular family, its outgrowth can be suppressed. Precedent for 'dominant drug targeting' as a deliberate approach to suppress the outgrowth of inhibitor-resistant viruses has been established for envelope variants of vesicular stomatitis virus and for capsid variants of poliovirus and dengue virus...
October 17, 2016: Current Opinion in Virology
Kuang-Po Li, Poa-Chun Chang, Ming-Chu Cheng, Duen-Huey Tan, Li-Hsuan Chen, Yu-Pin Liu, Yu-Ju Lin, Hsiang-Jung Tsai, Jui-Hung Shien
The sequence at the hemagglutinin (HA) cleavage site (CS) plays a key role in determining the pathogenicity of avian influenza viruses. Three types of HA CS sequences, QREKR/GL, QRKKR/GL and QRRKR/GL, were previously reported in Taiwanese H5N2 viruses that were isolated from chickens from 2003 to 2013. However, no HA CS sequence was reported for viruses isolated after 2013. This article presents the HA CS sequences and pathogenicity of H5N2 viruses that were isolated from chickens in Taiwan during 2013-2015...
October 3, 2016: Journal of Veterinary Medical Science
Yuan Xue, Ming-Jie Wang, Su-Yuan Huang, Zhi-Tao Yang, De-Min Yu, Yue Han, Ming-Yu Zhu, Dao Huang, Dong-Hua Zhang, Qi-Ming Gong, Xin-Xin Zhang
BACKGROUND: CpG islands in hepatitis B virus (HBV) genome are potential targets for methylation mediated gene silencing, and may be involved in the pathogenesis of HBV infection. To date, their characteristics in HBV quasispecies (QS) remain largely unknown. The purpose of this study was to investigate the characteristics of CpG islands in HBV QS. METHODS: Forty patients diagnosed as acute hepatitis B (AHB, n = 10), immune-tolerant HBV carriers (IT, n = 9), chronic hepatitis B (CHB, n = 11), or acute on chronic liver failure (ACLF, n = 10), were enrolled in this case-control study...
2016: SpringerPlus
Josep Sardanyés, Regina Martínez, Carles Simó, Ricard Solé
The dynamics of heterogeneous tumor cell populations competing with healthy cells is an important topic in cancer research with deep implications in biomedicine. Multitude of theoretical and computational models have addressed this issue, especially focusing on the nature of the transitions governing tumor clearance as some relevant model parameters are tuned. In this contribution, we analyze a mathematical model of unstable tumor progression using the quasispecies framework. Our aim is to define a minimal model incorporating the dynamics of competition between healthy cells and a heterogeneous population of cancer cell phenotypes involving changes in replication-related genes (i...
October 6, 2016: Journal of Mathematical Biology
Susana Posada-Cespedes, David Seifert, Niko Beerenwinkel
Rapidly evolving RNA viruses prevail within a host as a collection of closely related variants, referred to as viral quasispecies. Advances in high-throughput sequencing (HTS) technologies have facilitated the assessment of the genetic diversity of such virus populations at an unprecedented level of detail. However, analysis of HTS data from virus populations is challenging due to short, error-prone reads. In order to account for uncertainties originating from these limitations, several computational and statistical methods have been developed for studying the genetic heterogeneity of virus population...
September 28, 2016: Virus Research
Matheus N Weber, Fernando V Bauermann, Cláudio W Canal, Darrell O Bayles, John D Neill, Julia F Ridpath
'HoBi'-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. Pestivirus strains exist as quasispecies (swarms of individual viruses) in infected animals and the viral populations making up the quasispecies differ widely in size and diversity in each animal. In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time...
September 28, 2016: Virus Research
Jens Bukh
The discovery of hepatitis C virus (HCV) in 1989 permitted basic research to unravel critical components of a complex life cycle for this important human pathogen. HCV is a highly divergent group of viruses classified in 7 major genotypes and a great number of subtypes, and circulating in infected individuals as a continuously evolving quasispecies destined to escape host immune responses and applied antivirals. Despite the inability to culture patient viruses directly in the laboratory, efforts to define the infectious genome of HCV resulted in development of experimental recombinant in vivo and in vitro systems, including replicons and infectious cultures in human hepatoma cell lines...
October 2016: Journal of Hepatology
Adam Zuiani, Kevin Chen, Megan C Schwarz, James P White, Vincent C Luca, Daved H Fremont, David Wang, Matthew J Evans, Michael S Diamond
: While natural hepatitis C virus (HCV) infection results in highly diverse quasispecies of related viruses over time, mutations accumulate more slowly in tissue culture, in part because of the inefficiency of replication in cells. To create a highly diverse population of HCV particles in cell culture and identify novel growth-enhancing mutations, we engineered a library of infectious HCV with all codons represented at most positions in the ectodomain of the E2 gene. We identified many putative growth adaptive mutations and selected nine highly represented E2 mutants for further study: Q412R, T416R, S449P, T563V, A579R, L619T, V626S, K632T, and L644I...
September 14, 2016: Journal of Virology
Juliana Cristina Santiago Bastos, Marina Aiello Padilla, Leonardo Cardia Caserta, Noelle Miotto, Aline Gonzalez Vigani, Clarice Weis Arns
Despite advances in therapy, hepatitis C virus (HCV) infection remains an important global health issue. It is estimated that a significant part of the world population is chronically infected with the virus, and many of those affected may develop cirrhosis or liver cancer. The virus shows considerable variability, a characteristic that directly interferes with disease treatment. The response to treatment varies according to HCV genotype and subtype. The continuous generation of variants (quasispecies) allows the virus to escape control by antivirals...
July 28, 2016: World Journal of Gastroenterology: WJG
Xiaxia Zhang, Minran Li, Hongli Xi, Renwen Zhang, Jianhong Chen, Yu Zhang, Xiaoyuan Xu
AIMS: The dynamics of resistance-associated mutations under combination therapy were explored. METHODS: A total of 46 patients were classified into adefovir (n=14) and entecavir (n=32) groups. In the adefovir (ADV) group, six patients receiving combined therapy were DNA-positive after more than 3 years of therapy. Ultra-deep pyrosequencing was used to analyze the dynamics of multi-drugs resistance mutations. RESULTS: At baseline, all 46 treatment-naïve patients harbored rtA181V/T substitutions (1...
September 2, 2016: Oncotarget
Kazusato Ohshima, Rei Nomiyama, Shinichiro Mitoma, Yuki Honda, Ryosuke Yasaka, Kenta Tomimura
There is no attempt to evaluate evolutionary rates, timescales and diversities of viruses collected from mixedly infected hosts in nature. Plants of the genus Narcissus are a monocotyledon and are susceptible to several viruses. In this study, narcissus plants (Narcissus tazetta var. chinensis) showing mosaic or striping leaves were collected in Japan, and these were investigated for potyvirus infections using potyvirus-specific primers. Individual narcissus plants were found frequently to be mixedly infected with different potyviruses, different isolates and quasispecies of same virus...
August 31, 2016: Infection, Genetics and Evolution
Fanming Jiang, Xiaoxu Han, Hui Zhang, Bin Zhao, Minghui An, Junjie Xu, Zhenxing Chu, Tao Dong, Hong Shang
BACKGROUND: The purpose of this study was to characterize specific cytotoxic T-cell (CTL) responses in men who have sex with men (MSM) subjects infected with the human immunodeficiency virus type 1 (HIV-1) CRF01_AE subtype during the first year of infection and impacts on viral control and evolution. RESULTS: Fifteen HIV-1 primary infected cases were recruited from Liaoning MSM prospective cohort. CTL responses to Gag, Pol and Nef proteins at 3 month and 1 year post infection were detected with Gamma interferon enzyme-linked immunospot (ELISPOT) assay using optimized consensus overlapping peptides, as well as the viral quasispecies sequences from the synchronous plasma...
2016: BMC Immunology
Sikhulile Moyo, Alain Vandormael, Eduan Wilkinson, Susan Engelbrecht, Simani Gaseitsiwe, Kenanao P Kotokwe, Rosemary Musonda, Frank Tanser, Max Essex, Vladimir Novitsky, Tulio de Oliveira
BACKGROUND: Cross-sectional, biomarker methods to determine HIV infection recency present a promising and cost-effective alternative to the repeated testing of uninfected individuals. We evaluate a viral-based assay that uses a measure of pairwise distances (PwD) to identify HIV infection recency, and compare its performance with two serologic incidence assays, BED and LAg. In addition, we assess whether combination BED plus PwD or LAg plus PwD screening can improve predictive accuracy by reducing the likelihood of a false-recent result...
2016: PloS One
Himanshu Manchanda, Nora Seidel, Markus F Blaess, Ralf A Claus, Joerg Linde, Hortense Slevogt, Andreas Sauerbrei, Reinhard Guthke, Michaela Schmidtke
Severe influenza associated with strong symptoms and lung inflammation can be caused by intra-host evolution of quasispecies with aspartic acid or glycine in hemagglutinin position 222 (HA-222D/G; H1 numbering). To gain insights into the dynamics of host response to this coevolution and to identify key mechanisms contributing to copathogenesis, the lung transcriptional response of BALB/c mice infected with an A(H1N1)pdm09 isolate consisting HA-222D/G quasispecies was analyzed from days 1 to 12 post infection (p...
2016: Frontiers in Microbiology
Ditte L Hedegaard, Damien C Tully, Ian A Rowe, Gary M Reynolds, David J Bean, Ke Hu, Christopher Davis, Annika Wilhelm, Colin B Ogilvie, Karen A Power, Alexander W Tarr, Deirdre Kelly, Todd M Allen, Peter Balfe, Jane A McKeating
BACKGROUND & AIMS: The high replication and mutation rate of hepatitis C virus (HCV) results in a heterogeneous population of viral sequences in vivo. HCV replicates in the liver and infected hepatocytes occur as foci surrounded by uninfected cells that may promote compartmentalization of viral variants. Given recent reports showing interferon stimulated gene (ISG) expression in chronic hepatitis C, we hypothesized that local interferon responses may limit HCV replication and evolution...
August 13, 2016: Journal of Hepatology
Magda Rybicka, Piotr Stalke, Krzysztof Piotr Bielawski
Chronic HBV infection affects more than 240 million people worldwide and is associated with a broad range of clinical manifestations including liver cirrhosis, liver failure and hepatocellular carcinoma. Because of the lack of an efficient cure for chronic hepatitis B, the main goal of antiviral therapy is the prevention of liver disease progression coupled with prolonged survival of patients. Because HBV viral load has been shown to be a crucial determinant of the progression of liver damage, these goals can be achieved as long as HBV replication can be suppressed...
September 2016: Reviews in Medical Virology
Widya Wasityastuti, Yoshihiko Yano, Dewiyani Indah Widasari, Laura Navika Yamani, Neneng Ratnasari, Didik Setyo Heriyanto, Rina Okada, Toshihito Tanahashi, Yoshiki Murakami, Takeshi Azuma, Yoshitake Hayashi
A nucleos(t)ide analog (NA) is the common antiviral drug available for directly treating hepatitis B virus (HBV) infection. However, its application has led to the emergence of NA-resistant mutations mostly in a conserved region of the reverse transcriptase domain of HBV polymerase. Harboring NA-resistant mutations decreases drug effectiveness and increases the frequency of end-stage liver disease. The invention of next-generation sequencing that can generate thousands of sequences from viral complex mixtures provides opportunities to detect minor changes and early viral evolution under drug stress...
2016: Kobe Journal of Medical Sciences
Xiaoyan Lu, Lori A Rowe, Michael Frace, James Stevens, Glen R Abedi, Osman El Nile, Taleb Banassir, Malak Al-Masri, John T Watson, Abdullah Assiri, Dean D Erdman
The spike glycoprotein of the Middle East respiratory coronavirus (MERS-CoV) facilitates receptor binding and cell entry. During investigation of a multi-facility outbreak of MERS-CoV in Taif, Saudi Arabia, we identified a mixed population of wild-type and variant sequences with a large 530 nucleotide deletion in the spike gene from the serum of one patient. The out of frame deletion predicted loss of most of the S2 subunit of the spike protein leaving the S1 subunit with an intact receptor binding domain. This finding documents human infection with a novel genetic variant of MERS-CoV present as a quasispecies...
August 2, 2016: Journal of Medical Virology
Fuxiao Liu, Xiaodong Wu, Lin Li, Yanli Zou, Shan Liu, Zhiliang Wang
The genus Morbillivirus is classified into the family Paramyxoviridae, and is composed of 6 members, namely measles virus (MV), rinderpest virus (RPV), peste-des-petits-ruminants virus (PPRV), canine distemper virus (CDV), phocine distemper virus (PDV) and cetacean morbillivirus (CeMV). The MV, RPV, PPRV and CDV have been successfully attenuated through their serial passages in vitro for the production of live vaccines. It has been demonstrated that the morbilliviral virulence in animals was progressively attenuated with their consecutive passages in vitro...
August 2016: Comparative Immunology, Microbiology and Infectious Diseases
Carol L Ecale Zhou
Modeling the molecular mechanisms that govern genetic variation can be useful in understanding the dynamics that drive genetic state transition in quasispecies viruses. For example, there is considerable interest in understanding how the relatively benign vaccine strains of poliovirus eventually revert to forms that confer neurovirulence and cause disease (ie, vaccine-derived poliovirus). This report describes a stochastic simulation model, S2M, which can be used to generate hypothetical outcomes based on known mechanisms of genetic diversity...
2016: Bioinformatics and Biology Insights
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