HOP/STIP1 is required for KSHV lytic replication

Kaposi sarcoma associated herpesvirus (KSHV) is a DNA virus that causes Kaposi sarcoma, a cancer of endothelial origin. KSHV uses the activity of host molecular chaperones like Hsp70 and Hsp90 for the folding of host and viral proteins required for productive infection. Hsp70 and Hsp90 chaperones form proteostasis networks with several regulatory proteins known as co-chaperones. Of these, Hsp90-Hsp70 organising protein (HOP) is an early-stage co-chaperone that regulates transfer of folding substrate proteins between the Hsp70 and Hsp90 chaperone systems. While roles for Hsp90 and Hsp70 in KSHV biology have been described, HOP has not previously been studied in this context despite its prominent interaction with both chaperones. Here we demonstrate a novel function for HOP as a new host factor required for effective lytic replication of KSHV in primary effusion cell lines.