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Evolution
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
The term quasispecies, defining the clouds of related elements that behave almost, or quasi, like a single type of molecule, or species, was used for the first time in the exhaustive review written by Domingo et al. (1985). The authors emphasized that cloned or non-cloned populations of most RNA viruses did not consist of a single genome species of defined sequence, but rather of heterogeneous mixtures of related genomes, or quasispecies. Due to very high mutation rates, the genomes of a quasispecies virus population shared a consensus sequence but differed from each other and from the consensus sequence by one, several, or many mutations. Needless to say, the quasispecies structure of the RNA virus populations should have many important theoretical and practical implications, because mutations at only one or a few sites might alter the phenotype of an RNA virus. It is noteworthy that the classical review of Esteban Domingo and John J. Holland (1988) was reprinted after 30 years by CRC Press (Domingo and Holland 2018).
Protease, Polymerase, and Assembly Inhibitors for the Treatment of Hepatitis C Virus Infection
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Marianne Martinello, Jason Grebely, Gregory Dore
Genotypic resistance analysis is based on DNA sequencing technologies that convert RNA genomes to DNA via reverse- transcription enzymes. Population sequencing of the HCV genome detects viral variants at a frequency of approximately 20% within the HCV quasispecies, while clonal and deep sequencing technologies allow detection of viral variants at a frequency of 0.5–1% (Dietz et al., 2013). The term quasispecies indicates that the population of HCV virions either in vitro or in vivo is a constellation of virions with varying genomes, not a monoclade. The variation within the clade is due to the error proneness of the RNA polymerase, and its extent depends largely on the duration of infection. It remains unclear as to which frequency cutoff for resistant mutations is most clinically relevant for prediction of virologic failure.
Animal Models of Viral Encephalitis
Published in Sunit K. Singh, Daniel Růžek, Neuroviral Infections, 2013
The basis for specific molecular interactions (e.g., virus—host receptor) between encephalitis viruses and components of the brain vasculature is generally lacking. While some molecular aspects of leukocyte trafficking across BMECs are known, in ways relevant to the subject of viruses that transit in leukocytes, specific mechanisms that relate to interactions between free virions and BMEC receptors are lacking. On the contrary, as shown for PV, circulating virus may cross the BBB in ways that involve a less specific manner. This was demonstrated in a mouse model in which invasion of PV across the BBB of transgenic mice expressing the human PV receptor occurred independent of the virus receptor (Yang et al. 1997). It is hard to predict the nature of such nonspecific mechanisms, however, and perhaps equally hard to prove that no additional receptors exist on these cells. Another interesting aspect of viral neuroinvasion suggested by PV-infected mice recently is that virus quasispecies, that is, variants of a given virus within a host, cooperate in order to facilitate the entry of neurovirulent members (Orandle et al. 2002; Vignuzzi et al. 2006). The exact role that virus quasispecies might play in neuroinvasion, however, requires much work to understand.
Recent advances in the understanding of enterovirus A71 infection: a focus on neuropathogenesis
Published in Expert Review of Anti-infective Therapy, 2021
Han Kang Tee, Mohd Izwan Zainol, I-Ching Sam, Yoke Fun Chan
Like other RNA viruses, EV-A71 generates a swarm of variants termed quasispecies during infection [122,123]. Quasispecies refers to the subpopulation variants generated during replication, with one or two mismatched nucleotides differing from the parental virus [124]. The occurrence of quasispecies is due to the high mutation rate of RNA viruses, which could be related to the low fidelity (error-prone) nature of viral RNA-dependent RNA polymerases (RdRp) [125,126]. It is essential to maintain viral population heterogeneity during pathogenesis. Taking the example of PV, a high-fidelity PV variant containing a G64S mutation at RdRp displayed attenuated virulence in mice due to its restricted quasispecies [127]. However, virulence was restored by applying a chemical mutagen to the G64S viral population before infecting the mice. Using a similar strategy, a high-fidelity EV-A71 variant (containing G64R and L123F mutations) also exhibited an attenuated virulent phenotype in mice, suggesting that viral diversity plays an important role in altering the outcome of neurovirulence [128]. A similar result was also obtained with the introduction of high-fidelity and recombination-deficient mutations which rendered a virulent EV-A71 strain (harboring VP1-Q145 and VP1-E244) avirulent in mice [66].
Next-generation sequencing for the diagnosis of hepatitis B: current status and future prospects
Published in Expert Review of Molecular Diagnostics, 2021
Selene Garcia-Garcia, Maria Francesca Cortese, Francisco Rodríguez-Algarra, David Tabernero, Ariadna Rando-Segura, Josep Quer, Maria Buti, Francisco Rodríguez-Frías
Aside from the widely employed SGS platforms, few studies to date have used TGS technologies to analyze HBV variability, mainly due to their high error rate. Sequence output can be biased both by the need for prior DNA amplification and by representation of the rc-DNA reservoir rather than cccDNA [57]. As described above in more detail, McNaughton et al. compared Illumina and Nanopore deep-sequencing approaches for whole-genome sequencing (WGS) of HBV by generating concatemeric sequences, illustrating the feasibility of long-read data for complete haplotype reconstruction [40]. Although further optimization is still necessary for detecting mixed infections with minor variants, sequencing complete virus genomes in depth, while also preserving mutation-linkage information (i.e. complete haplotypes), remains an important goal [40]. Such data will inform more accurate phylogenetic characterizations of viral quasispecies within infected hosts, which can, in turn, be exploited to study virus transmission and the evolutionary dynamics of drug and immune escape [57].
Effect of the baseline Y93H resistance-associated substitution in HCV genotype 3 for direct-acting antiviral treatment: real-life experience from a multicenter study in Sweden and Norway
Published in Scandinavian Journal of Gastroenterology, 2019
Midori Kjellin, Hege Kileng, Dario Akaberi, Navaneethan Palanisamy, Ann-Sofi Duberg, Astrid Danielsson, Magnhild Gangsøy Kristiansen, Johan Nöjd, Soo Aleman, Tore Gutteberg, Rasmus Goll, Anders Lannergård, Johan Lennerstrand
Population-based sequencing generates a consensus sequence of the viral quasispecies with a sensitivity of approximately 20% for (minority) variants, recognised as mixed peaks in the electropherogram. The NS5A sequence results were aligned and analysed using SeqScape® Software v2.6 (Applied Biosystems™, Thermo Fisher Scientific, Waltham, MA, USA) to generate consensus sequences. The NS5A sequence of HCV GT1a H77 strain (accession number: NC_004102.1) was used as a reference template to which the sample sequences were aligned. To simplify, we considered this reference GT 1a template suitable for GT 3 during the analysis with the Seqscape software as described in a previous reports [7,29,30]. However, later on, the results were compared with GT 3a specific reference strain: D17763 (NZL1).