Smurf2 alters BPV1 trafficking and decreases infection

Abstract

Papillomavirus capsid proteins L1 and L2 mediate virion attachment, internalization and trafficking. In our studies of the capsid proteins, we identified an interaction of L2 with the E3 ligase Smad ubiquitin regulatory factor 2 (Smurf2). Smurf2 expression alters BPV1 virion trafficking and L2 protein levels. Using BPV1 pseudovirions (PSVs) containing a GFP or DSRed transgene encapsidated by L1 and L2 proteins, our data showed that although only BPV1 L2 interacts with Smurf2, both L1 and L2 levels decrease in a Smurf2- and ubiquitin-dependent manner. The decrease in L2 protein levels corresponded to a decrease in infection (i.e., loss of GFP or DSRed expression). We propose that Smurf2 regulates L2 protein cellular localization and therefore alters L2 protein levels. This change in trafficking and protein level decreases nuclear delivery and transcription of encapsidated pseudoviral transgenes and thus decreases BPV1 infection levels.