Rab14 regulates the transport of human papillomavirus to the trans-Golgi network for infectious cell entry.

Human papillomavirus (HPV) utilizes multiple host proteins to infect epithelial cells. Here we identified Rab14, a small GTPase belonging to the Rab family, as a critical host factor in HPV infection. Rab14 knockout (KO) cells exhibited resistance to HPV pseudovirion (PsV) infection. Confocal microscopy revealed that PsV transport to the trans-Golgi network (TGN) was significantly reduced in Rab14 KO cells. Reintroduction of wild-type Rab14 restored infection levels, but neither GDP-bound (S25N) nor GTP-bound (Q70L) mutants did. S25N preferentially localized to the TGN, while Q70L exhibited similar localization in the early endosome and the TGN. PsV showed reduced colocalization with S25N, whereas the opposite was observed for Q70L. These results indicate that Rab14 GTPase cycling controls HPV transport to the TGN.