Evolution of hepatitis C virus (HCV) hypervariable region 1 in immunocompetent children born to HCV-infected mothers

GISMONDI, M. I.; BECKER, P.; DIAZ CARRASCO, J. M.; GUZMÁN, C.; CAMPOS, R.; MARIA VICTORIA PRECIADO

JOURNAL OF VIRAL HEPATITIS.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Oxford; Año: 2009 vol. 16 p. 332 - 339

1352-0504

Hepatitis C virus (HCV) hypervariable region 1 (HVR1) is the most variable region of the viral genome and its heterogeneity reflects the virus-host interplay during chronicity. Paediatric HCV-infected patients develop a liver disease with typical clinical features. Here, the evolution of HVR1 and its adjacent regions was ascertained in plasma samples of two HCV-positive children during a 5-year follow-up. We report an almost complete conservation of HVR1 sequence over time, with underlying nucleotide variability both within and outside HVR1, suggesting some kind of constraint on virus evolution, particularly within HVR1. Although overall dN/dS rates were <1 in both patients, a high resolution analysis of selection pressures exerted at the codon level revealed few sites subject to selection and an absolute predominance of invariable positions within HVR1. The HVR1 amino acid sequences showed the antigenic properties expected for this region. Taken together, these data suggest a peculiar evolutionary dynamics in our patients, which could be attributed to a mechanism of nucleotide invariability along with purifying selection operating on the HVR1. The lack of HVR1 variability may reflect the adaptation of the virus to a particular environment within each patient or a phenomenon of immune tolerance generated in our immunocompetent patients early in life.