Differences in the regulatory and functional effects of the Us3 protein kinase activities of herpes simplex virus 1 and 2.
Us3 protein kinases encoded by herpes simplex virus 1 (HSV-1) and 2 (HSV-2) are serine/threonine protein kinases and play critical roles in viral replication and pathogenicity in vivo. In the present study, we investigated differences in the biological properties of HSV-1 and HSV-2 Us3 protein kinases and demonstrated that HSV-2 Us3 did not have some of the HSV-1 Us3 kinase functions, including control of nuclear egress of nucleocapsids, localization of UL31 and UL34, and cell surface expression of viral envelope glycoprotein B. In agreement with the observations that HSV-2 Us3 was less important for these functions, the effect of HSV-2 Us3 kinase activity on virulence in mice following intracerebral inoculation was much lower than that of HSV-1 Us3. Furthermore, we showed that alanine substitution in HSV-2 Us3 at a site (aspartic acid at position 147) corresponding to one that can be autophosphorylated in HSV-1 Us3 abolished HSV-2 Us3 kinase activity. Thus, the regulatory and functional effects of Us3 kinase activity are different between HSV-1 and HSV-2.
Morimoto
Tomomi
T
Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Arii
Jun
J
Tanaka
Michiko
M
Sata
Tetsutaro
T
Akashi
Hiroomi
H
Yamada
Masao
M
Nishiyama
Yukihiro
Y
Uema
Masashi
M
Kawaguchi
Yasushi
Y
D000818:Animals; D002522:Chlorocebus aethiops; D022202:Chromosomes, Artificial, Bacterial; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000472:pathogenicity; D018258:Herpesvirus 2, Human / Q000201:enzymology* / Q000472:pathogenicity; D051379:Mice; D008813:Mice, Inbred ICR; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000502:physiology; D019251:Nucleocapsid / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000096:biosynthesis; D014764:Viral Proteins / Q000502:physiology*; D014774:Virulence
D009687:Nuclear Proteins; C108721:UL31 protein, Human herpesvirus 1; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C040495:glycoprotein B, Simplexvirus; C044525:glycoprotein B, herpes simplex virus type 2; D017346:Protein Serine-Threonine Kinases; C095207:US3 protein, Human herpesvirus 1; C084395:US3 protein, Human herpesvirus 2