ZNF219, a novel transcriptional repressor, inhibits transcription of the prototype foamy virus by interacting with the viral LTR promoter.

• ZNF219 expression was downregulated in prototype foamy virus (PFV)-infected cells. • ZNF219 is a negative regulator of PFV transcription and replication. • ZNF219 was enriched in the viral 5'LTR region to inhibit the PFV 5'LTR promoter. • PFV infection triggered abnormal expression of miRNAs. • This permitted the inhibition of ZNF219 mRNA expression by miRNAs targeting ZNF219-3'UTR. Prototype foamy virus (PFV) is an ancient retrovirus that infects humans with persistent latent infections and non-pathogenic consequences. Lifelong latent PFV infections can be caused by restrictive factors in the host. However, the molecular mechanisms underlying host cell regulation during PFV infection are not fully understood. The aim of the study was to investigate whether a zinc finger protein (ZFP), ZNF219, as a transcription factor, can regulate the transcriptional activity of the viral promoter. Here, using transcriptome sequencing, we found that ZNF219, is downregulated in PFV infected cells and that ZNF219 suppresses viral replication by targeting the viral 5'LTR promoter region to repress its transcription. We also found that PFV infection induced abnormal expression of miRNAs targeting the ZNF219-3'UTR to downregulate ZNF219 expression. These findings indicated that ZNF219 may be a potent antiviral factor for suppressing PFV infection, and may shed light on the mechanism of virus-host interactions. [ABSTRACT FROM AUTHOR]