Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12666/388
Title: Dissimilar Conservation Pattern in Hepatitis C Virus Mutant Spectra, Consensus Sequences, and Data Banks
Authors: García Crespo, Carlos
Eugenia Soria, M.
Gallego, Isabel
Isabel de Ávila, A.
Martínez González, B.
Vázquez Sirvent, L.
Gómez, Jordi
Briones, C.
Gregori, Josep
Quer, J.
Perales, C.
Domingo, Esteban
Keywords: Antiviral Intervention;Consensus sequence;Mutant Spectrum;Residue conservation;Viral ligands;Virus data banks
Issue Date: 27-Oct-2020
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/jcm9113450
Published version: https://www.mdpi.com/2077-0383/9/11/3450
Citation: Journal of Clinical Medicine 9(11): 3450(2020)
Abstract: The influence of quasispecies dynamics on long-term virus diversification in nature is a largely unexplored question. Specifically, whether intra-host nucleotide and amino acid variation in quasispecies fit the variation observed in consensus sequences or data bank alignments is unknown. Genome conservation and dynamics simulations are used for the computational design of universal vaccines, therapeutic antibodies and pan-genomic antiviral agents. The expectation is that selection of escape mutants will be limited when mutations at conserved residues are required. This strategy assumes long-term (epidemiologically relevant) conservation but, critically, does not consider short-term (quasispecies-dictated) residue conservation. We calculated mutant frequencies of individual loci from mutant spectra of hepatitis C virus (HCV) populations passaged in cell culture and from infected patients. Nucleotide or amino acid conservation in consensus sequences of the same populations, or in the Los Alamos HCV data bank did not match residue conservation in mutant spectra. The results relativize the concept of sequence conservation in viral genetics and suggest that residue invariance in data banks is an insufficient basis for the design of universal viral ligands for clinical purposes. Our calculations suggest relaxed mutational restrictions during quasispecies dynamics, which may contribute to higher calculated short-term than long-term viral evolutionary rates.
URI: http://hdl.handle.net/20.500.12666/388
E-ISSN: 2077-0383
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