Species-specific KRAB-ZFPs function as repressors of retroviruses by targeting PBS regions

Proc Natl Acad Sci U S A. 2022 Mar 15;119(11):e2119415119. doi: 10.1073/pnas.2119415119. Epub 2022 Mar 8.

Abstract

SignificanceHosts often target the relatively conserved regions in rapidly mutating retroviruses to inhibit their replication. One of these regions is called a primer binding site (PBS), which has to be complementary to the host tRNA to initiate reverse transcription. By analyzing endogenous retroviral elements, we found that host cells use this sequence as a target in efforts to block the expression of viral elements. A specific type of zinc finger protein targets the PBS in a host genome, which not only inhibits the transcription of endogenous viruses but also inhibits the replication of exogenous retroviruses with the same PBS. Thus, our study sheds light on a strategy for searching for host restriction factors targeting retroviruses.

Keywords: ERVs; KRAB-ZFPs; PBS-Lys.

MeSH terms

  • Base Sequence
  • Binding Sites
  • Chromosome Mapping
  • Endogenous Retroviruses
  • Gene Expression Regulation, Viral*
  • Genome-Wide Association Study
  • Host-Pathogen Interactions*
  • Humans
  • Nucleotide Motifs
  • RNA, Viral / genetics*
  • RNA, Viral / metabolism*
  • Repressor Proteins / metabolism*
  • Retroviridae / classification
  • Retroviridae / physiology*
  • Transcription, Genetic
  • Virus Replication
  • Zinc Fingers*

Substances

  • RNA, Viral
  • Repressor Proteins