Distinct hepatitis B virus dynamics in the immunotolerant and early immunoclearance phases.
J Virol
; 84(7): 3454-63, 2010 Apr.
Article
em En
| MEDLINE
| ID: mdl-20089644
ABSTRACT
Little is known about hepatitis B virus (HBV) diversity changes within a host during the immunotolerant phase of chronic HBV infection. Such knowledge, nevertheless, may help in understanding how host immunity and HBV interact at the early stage of infection. In this study, serial serum samples were collected from a long-term (>17 years) follow-up cohort of seven patients, and multiple copies of the full-length viral genome from serially sampled sera were recovered and analyzed. Viral genetic diversity was positively correlated with host immunity, represented by levels of alanine aminotransferase (ALT), but was negatively correlated with the viral copy number. During the immunotolerant phase, when the host immunity was feeble (ALT < 20 U/liter), viral nucleotide diversity decreased while copy numbers increased. Rates of evolutionary change derived for different patients were in a very narrow range (1.6 x 10(-5) to 5.4 x 10(-5)/site/year). As the disease progressed toward the immunoclearance phase (ALT > 20 U/liter), viral diversity increased but copy numbers decreased. Evolutionary rates varied among patients in accordance with their levels of ALT, ranging from 9.6 x 10(-6) to 3.2 x 10(-4)/site/year. More than half (19/32 sites) of positively selected sites resided in immune epitopes, suggesting their possible role in host immunity. Our results demonstrate that host immunity is a dominant factor in HBV evolution. Different selective forces, including immune-mediated positive selection and virus-mediated negative selection, operate in tandem in shaping viral population dynamics within a host.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus da Hepatite B
/
Hepatite B Crônica
Limite:
Adolescent
/
Child
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Virol
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Taiwan