Effects of phosphorylation of herpes simplex virus 1 envelope glycoprotein B by Us3 kinase in vivo and in vitro.
We recently reported that the herpes simplex virus 1 (HSV-1) Us3 protein kinase phosphorylates threonine at position 887 (Thr-887) in the cytoplasmic tail of envelope glycoprotein B (gB) (A. Kato, J. Arii, I. Shiratori, H. Akashi, H. Arase, and Y. Kawaguchi, J. Virol. 83:250-261, 2009; T. Wisner, C. C. Wright, A. Kato, Y. Kawaguchi, F. Mou, J. D. Baines, R. J. Roller and D. C. Johnson, J. Virol. 83:3115-3126, 2009). In the studies reported here, we examined the effect(s) of this phosphorylation on viral replication and pathogenesis in vivo and present data showing that replacement of gB Thr-887 by alanine significantly reduced viral replication in the mouse cornea and development of herpes stroma keratitis and periocular skin disease in mice. The same effects have been reported for mice infected with a recombinant HSV-1 carrying a kinase-inactive mutant of Us3. These observations suggested that Us3 phosphorylation of gB Thr-887 played a critical role in viral replication in vivo and in HSV-1 pathogenesis. In addition, we generated a monoclonal antibody that specifically reacted with phosphorylated gB Thr-887 and used this antibody to show that Us3 phosphorylation of gB Thr-887 regulated subcellular localization of gB, particularly on the cell surface of infected cells.
Imai
Takahiko
T
Department of Infectious Disease Control, International Research Center for Infectious, The University of Tokyo, Tokyo 108-8639, Japan.
Sagou
Ken
K
Arii
Jun
J
Kawaguchi
Yasushi
Y
D000818:Animals; D002522:Chlorocebus aethiops; D003316:Corneal Diseases / Q000821:virology; D018259:Herpesvirus 1, Human / Q000378:metabolism* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D016849:Keratitis, Herpetic / Q000821:virology; D051379:Mice; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012871:Skin Diseases / Q000821:virology; D013912:Threonine / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
D014759:Viral Envelope Proteins; D014764:Viral Proteins; C040495:glycoprotein B, Simplexvirus; D013912:Threonine; D017346:Protein Serine-Threonine Kinases; C095207:US3 protein, Human herpesvirus 1