Comparative gene expression profiling of pig‐derived <scp>iPSC</scp>‐like cells: Effects of induced pluripotency on expression of porcine endogenous retrovirus (PERV)

Godehardt, Antonia W.; Petkov, Stoyan; Gulich, Barbara; Fischer, Nicole; Niemann, Heiner; Tönjes, Ralf R.

doi:10.1111/xen.12429

Cited by 14 publications

(7 citation statements)

References 39 publications

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“… 52 However, in the porcine induced pluripotent stem cells (piPSCs), a 10–100-fold higher transcription of porcine ERV elements are observed than that in porcine fetal fibroblasts. 53 Therefore, porcine PSCs may possess the ERASE function as mESCs. More work is needed to characterize the ERASE activity in other mammalian species in the future.…”

Section: Discussionmentioning

confidence: 99%

Endogenous reverse transcriptase and RNase H-mediated antiviral mechanism in embryonic stem cells

Xing

et al. 2021

Cell Res

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Nucleic acid-based systems play important roles in antiviral defense, including CRISPR/Cas that adopts RNA-guided DNA cleavage to prevent DNA phage infection and RNA interference (RNAi) that employs RNA-guided RNA cleavage to defend against RNA virus infection. Here, we report a novel type of nucleic acid-based antiviral system that exists in mouse embryonic stem cells (mESCs), which suppresses RNA virus infection by DNA-mediated RNA cleavage. We found that the viral RNA of encephalomyocarditis virus can be reverse transcribed into complementary DNA (vcDNA) by the reverse transcriptase (RTase) encoded by endogenous retrovirus-like elements in mESCs. The vcDNA is negative-sense single-stranded and forms DNA/RNA hybrid with viral RNA. The viral RNA in the heteroduplex is subsequently destroyed by cellular RNase H1, leading to robust suppression of viral growth. Furthermore, either inhibition of the RTase activity or depletion of endogenous RNase H1 results in the promotion of virus proliferation. Altogether, our results provide intriguing insights into the antiviral mechanism of mESCs and the antiviral function of endogenized retroviruses and cellular RNase H. Such a natural nucleic acid-based antiviral mechanism in mESCs is referred to as ERASE (endogenous RTase/RNase H-mediated antiviral system), which is an addition to the previously known nucleic acid-based antiviral mechanisms including CRISPR/Cas in bacteria and RNAi in plants and invertebrates.

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Section: Discussionmentioning

confidence: 99%

Endogenous reverse transcriptase and RNase H-mediated antiviral mechanism in embryonic stem cells

Xing

et al. 2021

Cell Res

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“…Endogenous retroviruses have been found highly expressed in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) of humans and mice, and they were used as markers for pluripotency [87][88][89][90]. A high expression of PERV was also observed in pig iPSCs [91]. Therefore, it was very surprising to see that in expanded potential stem cells (EPSCs), the expression of PERV was extremely low [69].…”

Section: Pervs and Stem Cellsmentioning

confidence: 99%

Porcine Endogenous Retroviruses and Xenotransplantation, 2021

Denner

2021

Viruses

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Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs, and some of them are able to infect human cells. Therefore, PERVs pose a risk for xenotransplantation, the transplantation of pig cells, tissues, or organ to humans in order to alleviate the shortage of human donor organs. Up to 2021, a huge body of knowledge about PERVs has been accumulated regarding their biology, including replication, recombination, origin, host range, and immunosuppressive properties. Until now, no PERV transmission has been observed in clinical trials transplanting pig islet cells into diabetic humans, in preclinical trials transplanting pig cells and organs into nonhuman primates with remarkable long survival times of the transplant, and in infection experiments with several animal species. Nevertheless, in order to prevent virus transmission to the recipient, numerous strategies have been developed, including selection of PERV-C-free animals, RNA interference, antiviral drugs, vaccination, and genome editing. Furthermore, at present there are no more experimental approaches to evaluate the full risk until we move to the clinic.

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“…Infectious risks can exist in any cell and organ, but interestingly some have higher levels of PERV than others. Godehardt et al provide insight into porcine induced pluripotent stem cells (piPSCs), finding that they have elevated levels of PERV when compared to non‐induced cells. Since PSCs are found in all organs and have been considered as an option in xenotransplantation, this grants new perspectives for future transplants.…”

Section: New Testsmentioning

confidence: 99%