Movements of Ancient Human Endogenous Retroviruses Detected in SOX2-Expressing Cells

Autor: Mizuki Goto, Takumi Era, Yorifumi Satou, Taku Kaitsuka, Tomoya Matsusako, Yoshikazu Uchiyama, Kazuhito Tomizawa, Tomohiro Sawa, Kazuaki Monde, Yosuke Maeda, Fan Yan Wei, Shinya Yamaga, Jumpei Ito, Hiromi Terasawa, Akira Ono, Ituro Inoue
Rok vydání: 2022
Předmět:
Zdroj: Journal of Virology. 96
ISSN: 1098-5514
0022-538X
DOI: 10.1128/jvi.00356-22
Popis: SummaryHuman endogenous retroviruses (HERVs) occupy approximately 8% of human genome. HERVs, which are transcribed in early embryos, are epigenetically silenced in somatic cells, except in pathological contexts. HERV-K is thought to protect the embryo from exogenous viral infection. However, uncontrollable HERV-K expression in somatic cells has been implicated in several diseases. Here, we show that SOX2, which plays a key role in maintaining pluripotency of stem cells, is critical for the transcription of HERV-K LTR5Hs. HERV-K can undergo retrotransposition within producer cells in the absence of Env expression. Furthermore, new HERV-K integration sites were identified in a long-term culture of induced pluripotent stem cells, which express SOX2. Together, these results suggest the possibility that the strict dependence of HERV-K on SOX2 have allowed contribution of HERV-K to the protection of early embryos during evolution while limiting potentially harmful effects of HERV-K retrotransposition on host genome integrity to these early embryos.
Databáze: OpenAIRE