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https://www.readbyqxmd.com/read/28680115/identification-of-hcv-resistant-variants-against-direct-acting-antivirals-in-plasma-and-liver-of-treatment-na%C3%A3-ve-patients
#1
V Stalin Raj, Gadissa Bedada Hundie, Anita C Schürch, Saskia L Smits, Suzan D Pas, Sophie Le Pogam, Harry L A Janssen, Rob J de Knegt, Albert D M E Osterhaus, Isabel Najera, Charles A Boucher, Bart L Haagmans
Current standard-of-care treatment of chronically infected hepatitis C virus (HCV) patients involves direct-acting antivirals (DAA). However, concerns exist regarding the emergence of drug -resistant variants and subsequent treatment failure. In this study, we investigate potential natural drug-resistance mutations in the NS5B gene of HCV genotype 1b from treatment-naïve patients. Population-based sequencing and 454 deep sequencing of NS5B gene were performed on plasma and liver samples obtained from 18 treatment- naïve patients...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28650844/long-term-persistence-of-hcv-ns5a-resistance-associated-substitutions-after-treatment-with-the-hcv-ns5a-inhibitor-ledipasvir-without-sofosbuvir
#2
David Wyles, Alessandra Mangia, Wendy Cheng, Stephen Shafran, Christian Schwabe, Wen Ouyang, Charlotte Hedskog, John McNally, Diana M Brainard, Brian P Doehle, Evguenia Svarovskaia, Michael D Miller, Hongmei Mo, Hadas Dvory-Sobol
BACKGROUND: Data on persistence of NS5A resistance associated substitutions (RASs) may have implications for resistance testing approaches and selection of initial and retreatment strategies. METHODS: Long-term persistence of NS5A RASs in HCV genotype (GT) 1 infected subjects (n=76) who did not achieve sustained virologic response after receiving ledipasvir (LDV) without sofosbuvir (SOF) and were subsequently enrolled in an ongoing 3-year follow-up registry study was investigated by population or deep sequencing...
June 26, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28637761/mother-to-child-hiv-transmission-bottleneck-selects-for-consensus-virus-with-lower-gag-protease-driven-replication-capacity
#3
Vanessa L Naidoo, Jaclyn K Mann, Christie Noble, Emily Adland, Jonathan M Carlson, Jake Thomas, Chanson J Brumme, Christina F Thobakgale-Tshabalala, Zabrina L Brumme, Mark A Brockman, Philip J R Goulder, Thumbi Ndung'u
HIV infection is in the large majority of cases established by a single variant and understanding the characteristics of successfully transmitted variants is relevant to prevention strategies. Few studies have investigated the viral determinants of mother-to-child transmission. To determine the impact of Gag-protease driven viral replication capacity on mother-to-child transmission, the replication capacities of 148 recombinant viruses encoding plasma derived Gag-protease from 53 non-transmitter mothers, 48 transmitter mothers and 47 infected infants were assayed in an HIV-1 inducible green fluorescent protein reporter cell line...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28635289/exploring-the-drug-resistance-of-hcv-protease
#4
Garima Jindal, Dibyendu Mondal, Arieh Warshel
Hepatitis C virus (HCV) currently affects several million people across the globe. One of the major classes of drugs against HCV inhibits the NS3/4A protease of the polyprotein chain. Efficacy of these drugs is severely limited due to the high mutation rate that results in several genetically related quasispecies. The molecular mechanism of drug resistance is frequently deduced from structural studies and binding free energies. However, prediction of new mutations requires the evaluation of both binding free energy of the drug as well as the parameters (kcat and KM) for the natural substrate...
July 5, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28634353/coronavirus-hku15-in-respiratory-tract-of-pigs-and-first-discovery-of-coronavirus-quasispecies-in-5-untranslated-region
#5
Patrick Cy Woo, Susanna Kp Lau, Chi-Ching Tsang, Candy Cy Lau, Po-Chun Wong, Franklin Wn Chow, Jordan Yh Fong, Kwok-Yung Yuen
Coronavirus HKU15 is a deltacoronavirus that was discovered in fecal samples of pigs in Hong Kong in 2012. Over the past three years, Coronavirus HKU15 has been widely detected in pigs in East/Southeast Asia and North America and has been associated with fatal outbreaks. In all such epidemiological studies, the virus was generally only detected in fecal/intestinal samples. In this molecular epidemiology study, we detected Coronavirus HKU15 in 9.6% of the nasopharyngeal samples obtained from 249 pigs in Hong Kong...
June 21, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28630115/discovering-complete-quasispecies-in-bacterial-genomes
#6
Frederic Bertels, Chaitanya S Gokhale, Arne Traulsen
Mobile genetic elements can be found in almost all genomes. Possibly the most common non-autonomous mobile genetic elements in bacteria are REPINs that can occur hundreds of times within a genome. The sum of all REPINs in a genome can be viewed as an evolving population because REPINs replicate and mutate. In contrast to most other biological populations, we know the exact composition of the REPIN population and the sequence of each member of the population. Here, we model the evolution of REPINs as quasispecies...
June 19, 2017: Genetics
https://www.readbyqxmd.com/read/28613145/two-novel-dromedary-camel-bocaparvoviruses-from-dromedaries-in-the-middle-east-with-unique-genomic-features
#7
Patrick C Y Woo, Susanna K P Lau, Hoi-Wah Tsoi, Nissy Georgy Patteril, Hazel C Yeung, Sunitha Joseph, Emily Y M Wong, Rubeena Muhammed, Franklin W N Chow, Ulrich Wernery, Kwok-Yung Yuen
The recent emergence of Middle East respiratory syndrome (MERS) coronavirus and its discovery from dromedary camels has boosted interest in the search for novel viruses in dromedaries. While bocaparvoviruses are known to infect various animals, it was not known that they exist in dromedaries. In this study, we describe the discovery of two novel dromedary camel bocaparvoviruses (DBoVs), DBoV1 and DBoV2, from dromedary faecal samples in Dubai. Among 667 adult dromedaries and 72 dromedary calves, 13.9 % of adult dromedaries and 33...
June 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28595635/the-pepper-virome-natural-co-infection-of-diverse-viruses-and-their-quasispecies
#8
Yeonhwa Jo, Hoseong Choi, Sang-Min Kim, Sun-Lim Kim, Bong Choon Lee, Won Kyong Cho
BACKGROUND: The co-infection of diverse viruses in a host plant is common; however, little is known about viral populations and their quasispecies in the host. RESULTS: Here, we report the first pepper viromes that were co-infected by different types of viral genomes. The pepper viromes are dominated by geminivirus DNA-A followed by a novel carlavirus referred to as Pepper virus A. The two pepper cultivars share similar viral populations and replications. However, the quasispecies for double-stranded RNA virus and two satellite DNAs were heterogeneous and homogenous in susceptible and resistant cultivars, respectively, indicating the quasispecies of an individual virus depends on the host...
June 8, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28595606/detection-of-a-genetic-footprint-of-the-sofosbuvir-resistance-associated-substitution-s282t-after-hcv-treatment-failure
#9
Andreas Walker, Sandra Filke, Nadine Lübke, Martin Obermeier, Rolf Kaiser, Dieter Häussinger, Jörg Timm, Hans H Bock
BACKGROUND: The major resistance-associated substitution for sofosbuvir (S282T) in HCV NS5B causes severe viral fitness costs and rapidly reverts back to prototype in the absence of selection pressure. Accordingly, resistance against sofosbuvir is rarely detected even in patients after treatment failure. CASE PRESENTATION: We report a case of a GT3a infected patient with viral breakthrough under SOF/DCV therapy. At the time of breakthrough the RAS S282T was predominant in NS5B and then rapidly disappeared during follow-up by week 12 after treatment...
June 8, 2017: Virology Journal
https://www.readbyqxmd.com/read/28591184/occult-hepatitis-b-virus-infection-in-hiv-positive-patients-at-a-tertiary-healthcare-unit-in-eastern-india
#10
Debraj Saha, Ananya Pal, Neelakshi Sarkar, Dipanwita Das, Jason T Blackard, Subhasish Kamal Guha, Bibhuti Saha, Runu Chakravarty
Occult HBV infection (OBI), defined by the presence of HBV DNA in absence of hepatitis B surface antigen (HBsAg), is a significant concern in the HIV-infected population. Of 441 HIV+/HBsAg- patients analyzed, the overall prevalence of OBI was 6.3% (28/441). OBI was identified in 21 anti-HBc positives (17.8%), as well as among those who lacked any HBV-specific serological markers (2.2%). Comparison with HIV/HBV co-infection revealed that the levels of CD4, ALT, and HBV DNA were significantly lower during occult infection...
2017: PloS One
https://www.readbyqxmd.com/read/28547382/comparative-analysis-of-cherry-virus-a-genome-sequences-assembled-from-deep-sequencing-data
#11
Prasad Kesanakurti, Mark Belton, Hanaa Saeed, Heidi Rast, Ian Boyes, Michael Rott
Cherry virus A (CVA) is a ubiquitous graft-transmissible virus that mainly infects Prunus spp. Next-generation sequencing was applied to 39 tree fruit specimens infected with CVA, and 75 full and 16 partial-length CVA genome sequences were assembled. Phylogenetic analysis of these and 11 previously sequenced CVA genomes resulted in six major clusters with no observable relationship between the host and the assembled genome sequences. Recombination analysis detected four recombinants. Consistent single-nucleotide polymorphism (SNP) patterns were observed between the 75 full-length genomes and their sequence clouds, which supports a quasispecies model for CVA evolution...
May 25, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28539654/quasispecies-composition-and-evolution-of-a-typical-zika-virus-clinical-isolate-from-suriname
#12
Sander van Boheemen, Ali Tas, S Yahya Anvar, Rebecca van Grootveld, Irina C Albulescu, Martijn P Bauer, Mariet C Feltkamp, Peter J Bredenbeek, Martijn J van Hemert
The arthropod-borne Zika virus (ZIKV) is currently causing a major international public health threat in the Americas. This study describes the isolation of ZIKV from the plasma of a 29-year-old female traveler that developed typical symptoms, like rash, fever and headache upon return from Suriname. The complete genome sequence including the 5' and 3' untranslated regions was determined and phylogenetic analysis showed the isolate clustering within the Asian lineage, close to other viruses that have recently been isolated in the Americas...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28483405/quasispecies-characteristics-in-mother-to-child-transmission-of-hepatitis%C3%A2-b%C3%A2-virus-by-next-generation-sequencing
#13
Guifeng Yang, Zhihua Liu, Juncheng Yang, Kangxian Luo, Ying Xu, Haitang He, Qunfang Fu, Shouyi Yu, Zhanhui Wang
OBJECTIVES: To identify within-host quasispecies characteristics of hepatitis B virus (HBV) in mothers and children infected via mother-to-child transmission (MTCT). METHODS: Using next-generation sequencing (NGS), we analyzed sequences within the non-overlapping pre-core/core (pre-C/C) gene in 37 mother-child pairs. RESULTS: Phylogenetic and Highlighter analyses suggested that both a single strain and multiple distinct strains may be transmitted in MTCT of HBV...
May 5, 2017: Journal of Infection
https://www.readbyqxmd.com/read/28464889/highly-divergent-patterns-of-genetic-diversity-and-evolution-in-proviral-quasispecies-from-hiv-controllers
#14
Suwellen S D de Azevedo, Diogo Gama Caetano, Fernanda H Côrtes, Sylvia L M Teixeira, Karina Dos Santos Silva, Brenda Hoagland, Beatriz Grinsztejn, Valdilea G Veloso, Mariza G Morgado, Gonzalo Bello
BACKGROUND: Ongoing intra-host HIV-1 evolution has been shown in individuals that naturally suppress the viremia to low levels (HIV controllers) by the analysis of the RNA in plasma compartment. Detection of evolution at the DNA proviral compartment in HIV controllers, however, has been more challenging and the precise correlation between the systemic viral suppression level and rate of reservoir's reseeding in those individuals is not fully understood. In this sense, we examined the proviral DNA quasispecies by single genome amplification of the env gene in a cohort of 23 HIV controllers from Brazil, divided in three groups, according to the level of systemic viral suppression: (1) elite controllers with persistent undetectable viral load (PEC, n = 6); (2) elite controllers with occasional episodes of transient (51-400 copies/mL) viremia (EEC, n = 7); and (3) viremic controllers with persistent low-level (80-2000 copies/mL) viremia (VC, n = 10)...
May 2, 2017: Retrovirology
https://www.readbyqxmd.com/read/28446139/de-novo-assembly-of-highly-polymorphic-metagenomic-data-using-in-situ-generated-reference-sequences-and-a-novel-blast-based-assembly-pipeline
#15
You-Yu Lin, Chia-Hung Hsieh, Jiun-Hong Chen, Xuemei Lu, Jia-Horng Kao, Pei-Jer Chen, Ding-Shinn Chen, Hurng-Yi Wang
BACKGROUND: The accuracy of metagenomic assembly is usually compromised by high levels of polymorphism due to divergent reads from the same genomic region recognized as different loci when sequenced and assembled together. A viral quasispecies is a group of abundant and diversified genetically related viruses found in a single carrier. Current mainstream assembly methods, such as Velvet and SOAPdenovo, were not originally intended for the assembly of such metagenomics data, and therefore demands for new methods to provide accurate and informative assembly results for metagenomic data...
April 26, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28422783/lessons-learned-from-humoral-responses-of-hiv-patients
#16
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...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28401776/molecular-characteristics-of-the-envelope-of-vertically-transmitted-hiv-1-strains-from-infants-with-hiv-infection
#17
Manickam Ashokkumar, Manohar Nesakumar, Narayaniah Cheedarla, K K Vidyavijayan, Hemalatha Babu, Srikanth P Tripathy, Luke Elizabeth Hanna
Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years)...
June 19, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28396522/de-novo-assembly-of-viral-quasispecies-using-overlap-graphs
#18
Jasmijn A Baaijens, Amal Zine El Aabidine, Eric Rivals, Alexander Schönhuth
A viral quasispecies, the ensemble of viral strains populating an infected person, can be highly diverse. For optimal assessment of virulence, pathogenesis, and therapy selection, determining the haplotypes of the individual strains can play a key role. As many viruses are subject to high mutation and recombination rates, high-quality reference genomes are often not available at the time of a new disease outbreak. We present SAVAGE, a computational tool for reconstructing individual haplotypes of intra-host virus strains without the need for a high-quality reference genome...
May 2017: Genome Research
https://www.readbyqxmd.com/read/28396347/serotype-specific-interactions-among-functional-domains-of-dengue-virus-2-nonstructural-proteins-ns-5-and-ns3-are-crucial-for-viral-rna-replication
#19
Tadahisa Teramoto, Anuradha Balasubramanian, Kyung H Choi, Radhakrishnan Padmanabhan
Four serotypes of mosquito-borne dengue virus (DENV), evolved from a common ancestor, are human pathogens of global significance for which there is no vaccine or antiviral drug available. The N-terminal domain of DENV NS5 has guanylyltransferase and methyltransferase (MTase), and the C-terminal region has the polymerase (POL), all of which are important for 5'-capping and RNA replication. The crystal structure of NS5 shows it as a dimer, but the functional evidence for NS5 dimer is lacking. Our studies showed that the substitution of DENV2 NS5 MTase or POL for DENV4 NS5 within DENV2 RNA resulted in a severe attenuation of replication in the transfected BHK-21 cells...
June 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28395198/propagation-and-some-physiological-effects-of-citrus-bark-cracking-viroid-and-apple-fruit-crinkle-viroid-in-multiple-infected-hop-humulus-lupulus-l
#20
J Matoušek, K Siglová, J Jakše, S Radišek, Joseph R J Brass, T Tsushima, T Guček, G S Duraisamy, T Sano, G Steger
The hop metabolome important for the brewing industry and for medical purposes is endangered worldwide due to multiple viroid infections affecting hop physiology. Combinatorial biolistic hop inoculation with Citrus bark cracking viroid (CBCVd), Apple fruit crinkle viroid (AFCVd), Hop latent viroid, and Hop stunt viroid (HSVd) showed a low CBCVd compatibility with HSVd, while all other viroid combinations were highly compatible. Unlike to other viroids, single CBCVd propagation showed a significant excess of (-) over (+) strands in hop, tomato, and Nicotiana benthamiana, but not in citruses...
June 2017: Journal of Plant Physiology
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