The piRNA Response to Retroviral Invasion of the Koala Genome

Cell. 2019 Oct 17;179(3):632-643.e12. doi: 10.1016/j.cell.2019.09.002. Epub 2019 Oct 10.


Antisense Piwi-interacting RNAs (piRNAs) guide silencing of established transposons during germline development, and sense piRNAs drive ping-pong amplification of the antisense pool, but how the germline responds to genome invasion is not understood. The KoRV-A gammaretrovirus infects the soma and germline and is sweeping through wild koalas by a combination of horizontal and vertical transfer, allowing direct analysis of retroviral invasion of the germline genome. Gammaretroviruses produce spliced Env mRNAs and unspliced transcripts encoding Gag, Pol, and the viral genome, but KoRV-A piRNAs are almost exclusively derived from unspliced genomic transcripts and are strongly sense-strand biased. Significantly, selective piRNA processing of unspliced proviral transcripts is conserved from insects to placental mammals. We speculate that bypassed splicing generates a conserved molecular pattern that directs proviral genomic transcripts to the piRNA biogenesis machinery and that this "innate" piRNA response suppresses transposition until antisense piRNAs are produced, establishing sequence-specific adaptive immunity.

Keywords: AKV; KoRV-A; genome invasion; germ-line genome; koala; piRNA; piRNA clusters; retrovirus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • DNA Transposable Elements
  • Gammaretrovirus / genetics*
  • Gammaretrovirus / metabolism
  • Gammaretrovirus / pathogenicity
  • Gene Products, env / genetics
  • Gene Products, env / metabolism
  • Gene Products, gag / genetics
  • Gene Products, gag / metabolism
  • Gene Products, pol / genetics
  • Gene Products, pol / metabolism
  • Genome
  • Germ Cells / metabolism
  • Germ Cells / virology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phascolarctidae / genetics*
  • Phascolarctidae / virology
  • RNA Splicing
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism


  • DNA Transposable Elements
  • Gene Products, env
  • Gene Products, gag
  • Gene Products, pol
  • RNA, Antisense
  • RNA, Small Interfering