Paraspeckle modification, a potential route to novel antivirals.

The nucleus is a highly organised yet dynamic environment containing distinct membraneless nuclear bodies. Viruses can sequester, reorganise, or degrade nuclear bodies to enhance their replication. Understanding the intricate interplay between nuclear bodies and viruses will provide novel insights into nuclear body structure and function, opening new opportunities for therapeutic intervention. We have exciting data showing that paraspeckles are dramatically modified during Kaposi’s sarcoma-associated herpesvirus (KSHV) infection. These virus-modified paraspeckles (v-mPS) are ~10 times larger than their canonical counterparts, have an altered proteome and are relocalised around viral transcription and replication centres (vRTCs). Crucially, disruption of v-mPS dramatically reduce KSHV replication. We will examine how paraspeckle formation and function is hijacked by a virus, and how this relates to disease, addressing three key aims: 1: How does virus infection subvert paraspeckle biogenesis and composition? 2: What are the consequences of v-mPS formation for both the virus and host? 3: Is targeting v-mPS a viable therapeutic strategy? This will reveal the mechanistic and functional concepts that underpin virus-mediated manipulation of nuclear bodies. It will transform our understanding of how paraspeckle dysregulation relates to disease and lay the foundations for new therapeutic strategies for a human tumour virus.