Redundant Late Domain Functions of Tandem VP2 YPX 3 L Motifs in Nonlytic Cellular Egress of Quasi-enveloped Hepatitis A Virus
González-López O., Rivera-Serrano EE., Hu F., Hensley L., McKnight KL., Ren J., Stuart DI., Fry EE., Lemon SM.
Nonlytic release of hepatitis A virus (HAV) as exosome-like quasi-enveloped virions is a unique but incompletely understood aspect of the hepatovirus life cycle. Several lines of evidence indicate that the host protein ALIX is essential for this process. Tandem YPX 3 L “late domains” in the VP2 capsid protein could be sites of interaction with ALIX, but they are not accessible on the surface of an X-ray model of the extracellular capsid, raising doubts about this putative late domain function. Here, we describe YPX 3 L domain mutants that assemble capsids normally but fail to bind ALIX and be secreted as quasi-enveloped eHAV. Our data support late domain function for the VP2 YPX 3 L motifs and raise questions about the structure of the HAV capsid prior to and following quasi-envelopment.