Trans-Complementation of HBV RtM204I Mutant Replication by HBV Wild-type Polymerase

Overview

Journal Virology

Specialty Microbiology

Date 2009 Apr 23

PMID 19383566

Authors

Richard A Heipertz Jr

Jason L Starkey

Thomas G Miller

Jianming Hu

Harriet C Isom

Affiliations

Soon will be listed here.

Abstract

The function of the hepatitis B virus (HBV) wild-type (WT) polymerase (pol) expressed alone or in the context of the intact genome when interacting with HBV rtM204I in HepG2 cells was compared. We show that WT pol expression from a packaging-defective RNA can complement defective rtM204I pol activity resulting in increased levels of HBV replicative intermediates (RI). Analysis of the genetically marked genomes showed that this restoration resulted from trans-complementation, rather than recombination. In contrast, we demonstrate that enhanced levels of total HBV RI observed when cells were cotransduced with both WT and rtM204I baculoviruses were predominantly WT RI. In this case, WT pol was produced from a full-length pregenomic RNA (pgRNA). We conclude that the WT pol has the capacity to trans-complement the replication defect of rtM204I; however, when expressed from an authentic pgRNA, as in a mixed infection, pol may not trans-complement efficiently.

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