Detail publikace

Role of DNA Methylation in Expression and Transmission of Porcine Endogenous Retroviruses

MATOUŠKOVÁ, M. VESELÝ, P. DANIEL, P. MATTIUZZO, G. HECTOR, R. SCOBIE, L. TAKEUCHI, Y. HEJNAR, J.

Originální název

Role of DNA Methylation in Expression and Transmission of Porcine Endogenous Retroviruses

Typ

článek v časopise ve Web of Science, Jimp

Jazyk

angličtina

Originální abstrakt

Porcine endogenous retroviruses (PERV) represent a major safety concern in pig-to-human xenotransplantation. To date, no PERV infection of a xenograft recipient has been recorded; however, PERVs are transmissible to human cells in vitro. Some recombinants of the A and C PERV subgroups are particularly efficient in infection and replication in human cells. Transcription of PERVs has been described in most pig cells, but their sequence and insertion polymorphism in the pig genome impede identification of transcriptionally active or silenced proviral copies. Furthermore, little is known about the epigenetic regulation of PERV transcription. Here, we report on the transcriptional suppression of PERV by DNA methylation in vitro and describe heavy methylation in the majority of PERV 5= long terminal repeats (LTR) in porcine tissues. In contrast, we have detected sparsely methylated or nonmethylated proviruses in the porcine PK15 cells, which express human cell-tropic PERVs. We also demonstrate the resistance of PERV DNA methylation to inhibitors of methylation and deacetylation. Finally, we show that the high permissiveness of various human cell lines to PERV infection coincides with the inability to efficiently silence the PERV proviruses by 5=LTR methylation. In conclusion, we suggest that DNA methylation is involved in PERV regulation, and that only a minor fraction of proviruses are responsible for the PERV RNA expression and porcine cell infectivity.

Klíčová slova

LONG TERMINAL REPEAT; HUMAN-CELLS; TRANSCRIPTIONAL ACTIVITY; REPLICATION-COMPETENT; MINIATURE SWINE; NO EVIDENCE; IN-VITRO; BIOARTIFICIAL LIVER; MOLECULAR CLONES; TRANSGENIC PIGS

Autoři

MATOUŠKOVÁ, M.; VESELÝ, P.; DANIEL, P.; MATTIUZZO, G.; HECTOR, R.; SCOBIE, L.; TAKEUCHI, Y.; HEJNAR, J.

Vydáno

1. 11. 2013

ISSN

0022-538X

Periodikum

JOURNAL OF VIROLOGY

Ročník

87

Číslo

22

Stát

Spojené státy americké

Strany od

12110

Strany do

12120

Strany počet

11

URL

https://jvi.asm.org/content/87/22/12110.short

BibTex

@article{BUT107927,
  author="Magda {Matoušková} and Pavel {Veselý} and Petr {Daniel} and Giada {Mattiuzzo} and Ralph D. {Hector} and Linda {Scobie} and Yasuhiro {Takeuchi} and Jiří {Hejnar}",
  title="Role of DNA Methylation in Expression and Transmission of Porcine Endogenous Retroviruses",
  journal="JOURNAL OF VIROLOGY",
  year="2013",
  volume="87",
  number="22",
  pages="12110--12120",
  doi="10.1128/JVI.03262-12",
  issn="0022-538X",
  url="https://jvi.asm.org/content/87/22/12110.short"
}