Identification of cellular factors required for the budding of koala retrovirus

Sayumi Shimode1,†, Rie Nakaoka2,†, Shigeki Hoshino1, Masumi Abe3, Hiroko Shogen1, Jiro Yasuda3,4 and Takayuki Miyazawa1

1Laboratory of Signal Transduction, Department of Cell Biology, Institute for Virus Research, Kyoto University, 53 Shogoin‐Kawaharacho, Sakyo‐ku, Kyoto 606‐8507, Japan
2Department of Veterinary Pathology, School of Veterinary Medicine, Rakuno Gakuen University, 582 Bunkyodai‐Midorimachi, Ebetsu, Hokkaido 069‐8501, Japan
3Fifth Biology Section for Microbiology, First Department of Forensic Science, National Research Institute of Police Science, 6‐3‐1 Kashiwanoha, Kashiwa, Chiba 277‐0882, Japan
4Department of Emerging Infectious Disease, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852‐8523, Japan

Koala retrovirus (KoRV) is a unique gammaretrovirus that is currently endogenizing into its host and considered to be associated with leukemia, lymphoma and immunosuppression in koalas (Phascolactos cinereus). In this study, it was demonstrated that WWP2 or WWP2like E3 ubiquitin ligases possessing the WW domain closely related to WWP2 and Vps4A/B are involved in KoRV budding. These data suggest that KoRV Gag recruits the cellular endosomal sorting complex required for transport machinery through interaction of the PPPY Ldomain with the WW domain(s) of WWP2 and that progeny virions are released from cells by utilizing the multivesicular body sorting pathway.