Submit a Letter to the Editor for:
T F Baumert, S A Rogers, K Hasegawa, T J Liang
J Clin Invest. 1996;
98(10):2268
doi:10.1172/JCI119037
Abstract |
Full text
|
PDF
V
iral mutations have been implicated in alteration of the biological phenotype of hepatitis B virus (HBV). We recently cloned and sequenced the viral genome of an HBV strain associated with an outbreak of fulminant hepatitis (FH strain). The FH strain contained numerous mutations in all genomic regions and was functionally characterized by a more efficient encapsidation of pregenomic RNA leading to highly enhanced replication. To define the responsible mutation(s) for the enhanced replication, we introduced individual mutations of the FH strain into a wild-type construct by oligonucleotide-directed mutagenesis. Analysis of viral replication showed that two adjacent mutations in the HBV core promotor (C to T at nucleotide 1768 and T to A at nucleotide 1770) led to high level replication. Similar to the FH strain, this mutant displayed the phenotype of enhanced encapsidation of pregenomic RNA. Functional studies in an encapsidation assay demonstrated that the identified mutations resulted in a minor increase of pregenomic RNA transcription (two- to threefold) and a major transcription-independent enhancement (> 10-fold) of viral encapsidation. Our results demonstrate that the two adjacent mutations in the HBV core promotor region are responsible for the enhanced replication of the FH strain. These two mutations, outside the previously described encapsidation signal, core, and polymerase polypeptides, appeared to affect a novel genetic element involved in viral encapsidation.
Guidelines:
The Editorial Board will only consider letters that we deem relevant and of interest to our readers. We will not post data that have not been subjected to peer review, nor will we post letters that are essentially a reiteration of another letter. All accepted letters will be posted on our website within one week of acceptance. The Editors reserve the right to edit any letter for length, content, and clarity. Authors of all accepted letters will be asked to preview any changes. Authors will be notified by e-mail if their letters were not accepted. As this is a final decision, no appeals will be considered.
Specific requirements: All letters must be 400 words or fewer. You may enter the letter as plain text or HTML, if you wish. The author's name and e-mail address are required, and will be posted with the letter. All possible conflicts of interest must be noted, even if they are not posted. If you wish to include a figure (keep in mind that non-peer-reviewed data will not be posted), please contact the editor directly at editors@the-jci.org.
