TY - JOUR
T1 - Dissimilar conservation pattern in hepatitis c virus mutant spectra, consensus sequences, and data banks
AU - García-Crespo, Carlos
AU - Soria, María Eugenia
AU - Gallego, Isabel
AU - De Ávila, Ana Isabel
AU - Martínez-González, Brenda
AU - Vázquez-Sirvent, Lucía
AU - Gómez, Jordi
AU - Briones, Carlos
AU - Gregori, Josep
AU - Quer, Josep
AU - Perales, Celia
AU - Domingo, Esteban
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/11
Y1 - 2020/11
N2 - 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 insu_cient 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.
AB - 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 insu_cient 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.
KW - Antiviral intervention
KW - Consensus sequence
KW - Mutant spectrum
KW - Residue conservation
KW - Viral ligands
KW - Virus data banks
UR - http://www.scopus.com/inward/record.url?scp=85106199620&partnerID=8YFLogxK
U2 - 10.3390/jcm9113450
DO - 10.3390/jcm9113450
M3 - Article
AN - SCOPUS:85106199620
SN - 2077-0383
VL - 9
SP - 1
EP - 18
JO - Journal of clinical medicine
JF - Journal of clinical medicine
IS - 11
M1 - 3450
ER -