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Limitations to Replication of Hepatitis Delta Virus in Avian Cells
Journal article   Open access   Peer reviewed

Limitations to Replication of Hepatitis Delta Virus in Avian Cells

Jinhong Chang, Gloria Moraleda and John Taylor
Journal of virology, v 74(19), pp 8861-8866
01 Oct 2000
DOI: https://doi.org/10.1128/JVI.74.19.8861-8866.2000
PMID: 10982328
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1128/JVI.74.19.8861-8866.2000View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

ABSTRACT Human hepatitis delta virus (HDV) is a natural subviral agent that uses hepatitis B virus as a helper. Experimentally, HDV can be made to replicate in woodchucks, using woodchuck hepatitis B virus as a helper virus. Also, independent of such helper activity, replication of the HDV RNA genome can be achieved in many mammalian cells. In this study we examined whether such replication could also be achieved in avian cells. We used cotransfection strategies and initially found no detectable genome replication in chicken LMH cells relative to the mammalian cell line Huh7, used as a positive control. We also found that, in contrast to transfected Huh7 cells, the avian cell line was readily and efficiently killed by expression of the delta protein. Three strategies were used to reduce such killing: (i) the delta protein was expressed from a separate expression vector, the amount of which was then reduced as much as 33-fold; (ii) the protein was expressed transiently, using a promoter under tetracycline control; and (iii) the transfected cells were treated with Z-VAD-fmk, a broad-spectrum caspase inhibitor, which reduced cell killing. This last result indicated that cell killing occurred via an apoptotic pathway. After application of these three strategies to reduce cell killing, together with a novel procedure to improve the signal-to-noise ratio in Northern analyses, replication of the HDV genome was then detected in LMH cells. However, even after removal of obvious signs of toxicity, the amount was still >50 times lower than in the Huh7 cells. Our findings explain previous unsuccessful attempts to demonstrate replication of the HDV genome in avian cells and establish the precedent that in certain situations HDV replication can be cytotoxic.

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