title: Dynamic changes in viral population structure and compartmentalization during chronic hepatitis C virus infection in children.
abstract: Classic phylogenetic and modern population-based clustering methods were used to analyze hepatitis C virus (HCV) evolution in plasma and to assess viral compartmentalization within peripheral blood mononuclear cells (PBMCs) in 6 children during 3.2-9.6yr of follow-up. Population structure analysis of cloned amplicons encompassing hypervariable region 1 led to the distinction of two evolutionary patterns, one highly divergent and another one genetically homogeneous. Viral adaptability was reflected by co-evolution of viral communities switching rapidly from one to another in the context of divergence and stability associated with highly homogeneous communities which were replaced by new ones after long periods. Additionally, viral compartmentalization of HCV in PBMCs was statistically demonstrated, suggesting their role as a pool of genetic variability. Our results support the idea of a community-based structure of HCV viral populations during chronic infection and highlight a role of the PBMC compartment in the persistence of such structure.
authors.affiliation: Laboratorio de Biología Molecular, División Patología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina. Electronic address: mgismondi@cnia.inta.gov.ar.
authors.forename: María Inés
authors.initials: MI
authors.lastname: Gismondi
authors.forename: Juan María
authors.initials: JM
authors.lastname: Díaz Carrasco
authors.forename: Pamela
authors.initials: P
authors.lastname: Valva
authors.forename: Pablo Daniel
authors.initials: PD
authors.lastname: Becker
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Guzmán
authors.forename: Rodolfo Héctor
authors.initials: RH
authors.lastname: Campos
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Preciado
mesh_terms: D000293:Adolescent; D058448:Biota; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D005260:Female; D014644:Genetic Variation; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D010949:Plasma / Q000821:virology; D012367:RNA, Viral / Q000235:genetics; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA
chemical_list: D012367:RNA, Viral
keywords: Compartmentalization; Evolution; Hepatitis C virus; PBMC; Pediatric infection; Population structure