A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry

Wodrich, Harald; Henaff, Daniel; Jammart, Baptist; Segura-Morales, Carolina; Seelmeir, Sigrid; Coux, Olivier; Ruzsics, Zsolt; Wiethoff, Christopher M.; Kremer, Eric J.

How ubiquitylation of protein VI or interaction with Nedd4 ligases directs accumulation of Ads at MTOCs remains unknown. Ubiquitylated protein VI could be specifically recognized by cellular factors. Alternatively, recruitment of Nedd4.1 and/or Nedd4.2 by protein VI could result in the ubiquitylation of other cellular factors that constitute an efficient transport means used by the virus. Recent work has shown that some members of ESCRT-I become ubiquitylated when Nedd4.2 is overexpressed [18, 19] . Therefore, it is possible that Nedd4.2 (or other Nedd4-ligases) binding to protein VI could activate the ESCRT pathway via ubiquitylation. Whether membrane compartments or the ESCRT pathway plays a direct role in Ad virus transport during entry remains to be addressed. However, ESCRT components can be found at the endosomal compartments as well as associated with the centromeric region [47] . It is noteworthy that endosomal escape is also required for interferon induction by Ad via yet unknown mechanisms [48] . This pathway may also be related to protein interaction between protein VI and Nedd4-family ligases.