Provirus Silencing in Stem Cells: The Forbidden Regulators of Cell Fate

Abstract

The cryptic presence of a wide range of retroviruses with varying copy number holds biological significance for host reproduction and development. Most of the endogenous retroviruses with lost pathogenicity and replication ability still serve as transcriptional regulators of host cellular genes. These structural and functional features of proviruses present them as alternate promoters and enhancers for several host cellular genes involved in development and other biological processes. In addition, embryonic stem (ES) cells and induced pluripotent cells are known to effectively silence the expression of most of these proviruses through repressive epigenetic marks and proviral sequence heterochromatization, which is not a case for those of differentiated cells. In this review, we aim to dissect the underlying salient features of proviral silencing in embryonic stem cells and analyze the potential of these proviruses in cell fate determination.