TY - JOUR
T1 - In-Host Flat-like Quasispecies :
T2 - Characterization Methods and Clinical Implications
AU - Gregori i Font, Josep
AU - Colomer-Castell, Sergi
AU - Ibañez-Lligoña, Marta
AU - Garcia-Cehic, Damir
AU - Campos, Carolina
AU - Buti Ferret, Maria
AU - Riveiro Barciela, Mar
AU - Andrés, Cristina
AU - Piñana, Maria
AU - González-Sánchez, Alejandra
AU - Rodríguez Frías, Francisco
AU - Cortese, Maria Francesca
AU - Tabernero, David
AU - Rando-Segura, Ariadna
AU - Pumarola Suñé, Tomàs
AU - Esteban Mur, Juan Ignacio
AU - Antón Pagarolas, Andrés
PY - 2024/5/17
Y1 - 2024/5/17
N2 - The repeated failure to treat patients chronically infected with hepatitis E (HEV) and C (HCV) viruses, despite the absence of resistance-associated substitutions (RAS), particularly in response to prolonged treatments with the mutagenic agents of HEV, suggests that quasispecies structure may play a crucial role beyond single point mutations. Quasispecies structured in a flat-like manner (referred to as flat-like) are considered to possess high average fitness, occupy a significant fraction of the functional genetic space of the virus, and exhibit a high capacity to evade specific or mutagenic treatments. In this paper, we studied HEV and HCV samples using high-depth next-generation sequencing (NGS), with indices scoring the different properties describing flat-like quasispecies. The significance of these indices was demonstrated by comparing the values obtained from these samples with those from acute infections caused by respiratory viruses (betacoronaviruses, enterovirus, respiratory syncytial viruses, and metapneumovirus). Our results revealed that flat-like quasispecies in HEV and HCV chronic infections without RAS are characterized by numerous low-frequency haplotypes with no dominant one. Surprisingly, these low-frequency haplotypes (at the nucleotide level) exhibited a high level of synonymity, resulting in much lower diversity at the phenotypic level. Currently, clinical approaches for managing flat-like quasispecies are lacking. Here, we propose methods to identifying flat-like quasispecies, which represents an essential initial step towards exploring alternative treatment protocols for viruses resistant to conventional therapies.
AB - The repeated failure to treat patients chronically infected with hepatitis E (HEV) and C (HCV) viruses, despite the absence of resistance-associated substitutions (RAS), particularly in response to prolonged treatments with the mutagenic agents of HEV, suggests that quasispecies structure may play a crucial role beyond single point mutations. Quasispecies structured in a flat-like manner (referred to as flat-like) are considered to possess high average fitness, occupy a significant fraction of the functional genetic space of the virus, and exhibit a high capacity to evade specific or mutagenic treatments. In this paper, we studied HEV and HCV samples using high-depth next-generation sequencing (NGS), with indices scoring the different properties describing flat-like quasispecies. The significance of these indices was demonstrated by comparing the values obtained from these samples with those from acute infections caused by respiratory viruses (betacoronaviruses, enterovirus, respiratory syncytial viruses, and metapneumovirus). Our results revealed that flat-like quasispecies in HEV and HCV chronic infections without RAS are characterized by numerous low-frequency haplotypes with no dominant one. Surprisingly, these low-frequency haplotypes (at the nucleotide level) exhibited a high level of synonymity, resulting in much lower diversity at the phenotypic level. Currently, clinical approaches for managing flat-like quasispecies are lacking. Here, we propose methods to identifying flat-like quasispecies, which represents an essential initial step towards exploring alternative treatment protocols for viruses resistant to conventional therapies.
KW - Enhanced fitness
KW - Flat-like quasispecies
KW - Mutagens
KW - Near-flat
KW - Regular quasispecies
KW - Resistance-associated mutations (RAS)
KW - Viral treatment failures
UR - http://www.scopus.com/inward/record.url?scp=85194395785&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/9f279902-8136-3467-8351-8823602114e2/
U2 - 10.3390/microorganisms12051011
DO - 10.3390/microorganisms12051011
M3 - Article
C2 - 38792840
SN - 2076-2607
VL - 12
JO - Microorganisms
JF - Microorganisms
IS - 5
M1 - 1011
ER -