Distinct hepatitis B viral dynamics in the immunotolerant and early immunoclearance phases

[Guest guest]

J Virol. 2010 Jan 20. [Epub ahead of print]

Distinct hepatitis B viral dynamics in the immunotolerant and early

immunoclearance phases.

Wang HY, Chien MH, Huang HP, Chang HC, Wu CC, Chen PJ, Chang MH, Chen DS.

Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan;

Department of Medical Research, National Taiwan University Hospital, National

Taiwan University, Taipei, Taiwan; School of Medicine, National Taiwan

University, Taipei, Taiwan; Department of Pediatrics, National Taiwan University

Hospital, National Taiwan University, Taipei, Taiwan; Hepatitis Research Center,

National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.

Little is known about hepatitis B viral (HBV) diversity change 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

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 numbers. During the immunotolerant

phase, when the host immunity was feeble (ALT < 20 U/L), viral nucleotide

diversity decreased while copy numbers increased. Rates of evolutionary change

derived from 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/L), viral diversity increased, but copy numbers decreased.

Evolutionary rates varied among patients in accordance with their levels of ALT,

ranging 9.6 x 10(-6) to 3.2 - 10(-4)/site/year. More than half (19/32) of

positively selected sites were resided in immune epitopes, suggesting their

possible role under 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.

PMID: 20089644 [PubMed - as supplied by publisher]