Published online Mar 21, 2014. doi: 10.3748/wjg.v20.i11.2971
Revised: December 20, 2013
Accepted: February 20, 2014
Published online: March 21, 2014
Recent reports show that many cellular RNAs are processed to form circular species that are relatively abundant and resistant to host nucleases. In some cases, such circles actually bind host microRNAs. Such depletion of available microRNAs appears to have biological roles; for instance, in homeostasis and disease. These findings regarding host RNA circles support a speculative reappraisal of the origin and mode of replication of hepatitis delta virus, hepatitis delta virus (HDV), an agent with a small circular RNA genome; specifically, it is proposed that in hepatocytes infected with hepatitis B virus (HBV), some viral RNA species are processed to circular forms, which by a series of chance events lead to an RNA that can be both replicated by host enzymes and assembled, using HBV envelope proteins, to form particles some of which are infectious. Such a model also may provide some new insights into the potential pathogenic potential of HDV infections. In return, new insights into HDV might provide information leading to a better understanding of the roles of the host RNA circles.
Core tip: This article includes an evaluation of the hypothesis that in hepatocytes of patients chronically infected with hepatitis B virus, some viral RNA sequences can form small RNA circles, leading to the chance selection of one circle that becomes the progenitor of hepatitis delta virus.