State and role of SRC family kinases in replication of herpes simplex virus 1.
An earlier report showed that infected cell protein no. 0 (ICP0) of herpes simplex virus 1 (HSV-1) interacts with the SH3 domains of a recently discovered adaptor protein, CIN85. Here, we report the following. (i) ICP0 also interacts with other SH3 domain-containing proteins and, in particular, with nonneuronal members of the Src kinase family. (ii) HSV-1 infection enhanced the activating phosphorylation of Tyr416 of the members of the Src kinase family, modestly enhanced the kinase activity of Src, and posttranslationally modified at least one additional member of the Src kinase family by phosphorylation in a manner dependent on the viral gene products ICP0, unique short 3 (U(S)3), and unique long 13 (U(L)13). (iii) To define the roles of Src kinase family members, we examined the accumulation of viral proteins, DNA, and mRNA and virus yields from wild-type mouse embryo fibroblasts and sibling cells lacking Src, Fyn, and Yes (SYF-); a mutant cell line, +Src, in which Src was restored to SYF- cells; and the mutant cell line (CSK-) lacking the negative regulator Csk gene of the Src kinase family. Representative alpha, beta, and gamma2 proteins accumulated in the largest amounts in SYF- cells and the smallest amounts in +Src compared to wild-type cells. The CSK- cells yielded smaller amounts of the gamma2 protein and at least 10-fold less virus than wild-type cells. We conclude that HSV-1 proteins regulate the activities of Src family kinases to achieve optimal viral yields in the course of viral replication.
The Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, 910 East 58th Street, Chicago IL 60637, USA.
Yu
Y
Liang
Bernard
B
Roizman
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D005982:Glutathione Transferase / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*; D014709:Vero Cells; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D004279:DNA, Viral; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D005982:Glutathione Transferase; D019061:src-Family Kinases