TY - JOUR
T1 - Differences in the regulatory and functional effects of the Us3 protein kinase activities of herpes simplex virus 1 and 2
AU - Morimoto, Tomomi
AU - Arii, Jun
AU - Tanaka, Michiko
AU - Sata, Tetsutaro
AU - Akashi, Hiroomi
AU - Yamada, Masao
AU - Nishiyama, Yukihiro
AU - Uema, Masashi
AU - Kawaguchi, Yasushi
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
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U2 - 10.1128/JVI.00993-09
DO - 10.1128/JVI.00993-09
M3 - Article
C2 - 19740999
AN - SCOPUS:70350309676
VL - 83
SP - 11624
EP - 11634
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 22
ER -