Herpes simplex virus type 2 tegument protein UL56 relocalizes ubiquitin ligase Nedd4 and has a role in transport and/or release of virions.
BACKGROUND
The ubiquitin system functions in a variety of cellular processes including protein turnover, protein sorting and trafficking. Many viruses exploit the cellular ubiquitin system to facilitate viral replication. In fact, herpes simplex virus (HSV) encodes a ubiquitin ligase (E3) and a de-ubiquitinating enzyme to modify the host's ubiquitin system. We have previously reported HSV type 2 (HSV-2) tegument protein UL56 as a putative adaptor protein of neuronal precursor cell-expressed developmentally down-regulated 4 (Nedd4) E3 ligase, which has been shown to be involved in protein sorting and trafficking.


RESULTS
In this study, we visualized and characterized the dynamic intracellular localization of UL56 and Nedd4 using live-cell imaging and immunofluorescence analysis. UL56 was distributed to cytoplasmic vesicles, primarily to the trans-Golgi network (TGN), and trafficked actively throughout the cytoplasm. Moreover, UL56 relocalized Nedd4 to the vesicles in cells transiently expressing UL56 and in cells infected with HSV-2. We also investigated whether UL56 influenced the efficiency of viral replication, and found that extracellular infectious viruses were reduced in the absence of UL56.


CONCLUSIONS
These data suggest that UL56 regulates Nedd4 and functions to facilitate the cytoplasmic transport of virions from TGN to the plasma membrane and/or release of virions from the cell surface.
Ushijima
Yoko
Y
Department of Virology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. ushiy-5@med.nagoya-u.ac.jp
Goshima
Fumi
F
Kimura
Hiroshi
H
Nishiyama
Yukihiro
Y
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D002522:Chlorocebus aethiops; D022162:Cytoplasmic Vesicles / Q000737:chemistry; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D006056:Golgi Apparatus / Q000737:chemistry; D018258:Herpesvirus 2, Human / Q000502:physiology*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D000075702:Nedd4 Ubiquitin Protein Ligases; D021381:Protein Transport; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014709:Vero Cells; D014764:Viral Proteins / Q000378:metabolism*; D019065:Virus Assembly
D056827:Endosomal Sorting Complexes Required for Transport; C546869:UL56 protein, Human herpesvirus 2; D014764:Viral Proteins; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; D044767:Ubiquitin-Protein Ligases