TFF2 and Kaposi's sarcoma: Thus, while ORF75 acts primarily as a lytic gene in PEL cell lines, Sp proteins induce substantial constitutive ORF75 transcription in infected endothelial cells and this can account for its high expression in KS lesions.<h4>Author summary</h4>In our study, we explored KSHV ORF75, a tegument protein that is increasingly being appreciated as playing a vital role in KSHV replication and inactivating the innate immune response.