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Background <p>Foamy viruses (FVs) are capable of cross-species transmission to humans and establish latent infections without causing diseases. The transition between latent and lytic FV replication is regulated by the viral proteins Bet and Tas, which are expressed predominantly from the internal promoter (IP). Bet suppresses basal IP activity and initiates latency, whereas Tas activates the IP and the long terminal repeat (LTR) promoter and enables lytic infection. However, the mechanisms regulating the relative levels of Tas and Bet are not completely understood.</p> Results <p>We performed a yeast two-hybrid screen to identify Tas-interacting proteins and discovered an association of the splicing factor heterogeneous nuclear ribonucleoprotein F (hnRNPF) with Tas. We found that hnRNPF inhibits prototype foamy virus (PFV) replication by shifting the viral expression profile from Tas to Bet. Importantly, hnRNPF specifically recognizes a G-cluster II <i>cis</i>-acting element (GC-II) within the <i>tas</i>/<i>bet</i> pre-mRNA to promote its splicing into <i>bet</i> mRNA, thereby reducing the levels of the unspliced <i>tas</i> transcript. The viral Tas protein, which interacts with hnRNPF, also possesses this splicing-promoting activity. Tas acts by binding to its DNA target, the Tas responsive element (TRE), thereby recruiting the hnRNPF to nascent viral RNA to enhance splicing efficiency.</p> Conclusions <p>We conclude that PFV Tas regulates the expression of itself and the viral Bet protein through splicing of <i>tas/bet</i> pre-mRNA by recruiting the cellular splicing factor hnRNPF. We further propose that hnRNPF may play an important role in establishing PFV latency by assisting Tas in decreasing Tas levels and increasing Bet expression to shut down viral gene expression.</p>

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PFV Tas protein recruits hnRNPF to promote the splicing of tas/bet pre-mRNA

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月4日

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  • Shishun Wu,
  • Chenxi Liu,
  • Manman Qiu,
  • Juan Tan,
  • Wentao Qiao

摘要

Background

Foamy viruses (FVs) are capable of cross-species transmission to humans and establish latent infections without causing diseases. The transition between latent and lytic FV replication is regulated by the viral proteins Bet and Tas, which are expressed predominantly from the internal promoter (IP). Bet suppresses basal IP activity and initiates latency, whereas Tas activates the IP and the long terminal repeat (LTR) promoter and enables lytic infection. However, the mechanisms regulating the relative levels of Tas and Bet are not completely understood.

Results

We performed a yeast two-hybrid screen to identify Tas-interacting proteins and discovered an association of the splicing factor heterogeneous nuclear ribonucleoprotein F (hnRNPF) with Tas. We found that hnRNPF inhibits prototype foamy virus (PFV) replication by shifting the viral expression profile from Tas to Bet. Importantly, hnRNPF specifically recognizes a G-cluster II cis-acting element (GC-II) within the tas/bet pre-mRNA to promote its splicing into bet mRNA, thereby reducing the levels of the unspliced tas transcript. The viral Tas protein, which interacts with hnRNPF, also possesses this splicing-promoting activity. Tas acts by binding to its DNA target, the Tas responsive element (TRE), thereby recruiting the hnRNPF to nascent viral RNA to enhance splicing efficiency.

Conclusions

We conclude that PFV Tas regulates the expression of itself and the viral Bet protein through splicing of tas/bet pre-mRNA by recruiting the cellular splicing factor hnRNPF. We further propose that hnRNPF may play an important role in establishing PFV latency by assisting Tas in decreasing Tas levels and increasing Bet expression to shut down viral gene expression.