Herpesviruses persist as a parasitic actor among many species. These viral agents can rapidly seize control over host cells by influencing global gene expression. Through a process known as host shutoff, herpesviruses cause a widespread degradation event of host transcripts within the cytoplasm. Specifically, Kaposi Sarcoma associated herpesvirus (KSHV) encodes for an endoribonuclease, termed SOX, that orchestrates this manipulation of gene expression. We and others have discovered certain transcripts that escape this fate; we suggest that this is an active escape, where transcripts have 3’ UTR elements that disallow SOX cleavage. One of the escapees that has been found is that of C19ORF66, which encodes the protein known as Shiftless (SHFL). SHFL is a broadly characterized antiviral host factor that may also be stimulated via interferons. Through our investigation of SHFL during KSHV infection, we have also observed this host factor acting in opposition to viral agents. We have also uncovered that SHFL expression causes the loss of P-bodies, a constitutively present RNA granule. We postulate that SHFL ability to regulate P-bodies directly contributes towards its antiviral capacity and serves as a rare example of host-P-body regulation. Through further characterization of this pro-host factor, we hope to provide a deeper understanding of sub-cellular mechanisms and host gene expression during KSHV infection
