期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：2
页码：798-802
DOI：10.1073/pnas.0913498107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：To better define the mechanism(s) likely responsible for viral clearance during hepatitis B virus (HBV) infection, viral clearance was studied in a panel of immunodeficient mouse strains that were hydrodynamically transfected with a plasmid containing a replication-competent copy of the HBV genome. Neither B cells nor perforin were required to clear the viral DNA transcriptional template from the liver. In contrast, the template persisted for at least 60 days at high levels in NOD/Scid mice and at lower levels in the absence of CD4+ and CD8+ T cells, NK cells, Fas, IFN-gamma (IFN-{gamma}), IFN-alpha/beta receptor (IFN-[α]/{beta}R1), and TNF receptor 1 (TNFR1), indicating that each of these effectors was required to eliminate the transcriptional template from the liver. Interestingly, viral replication was ultimately terminated in all lineages except the NOD/Scid mice, suggesting the existence of redundant pathways that inhibit HBV replication. Finally, induction of a CD8+ T cell response in these animals depended on the presence of CD4+ T cells. These results are consistent with a model in which CD4+ T cells serve as master regulators of the adaptive immune response to HBV; CD8+ T cells are the key cellular effectors mediating HBV clearance from the liver, apparently by a Fas-dependent, perforin-independent process in which NK cells, IFN-{gamma
关键词：viral persistance ; HBV clearance ; liver ; T cell ; in vivo transfection
