Protein Kinase B/Akt Is Present in Activated Form throughout the Entire Replicative Cycle of ΔU S 3 Mutant Virus but Only at Early Times after Infection with Wild-Type Herpes Simplex Virus 1
ABSTRACT The product of the herpes simplex virus 1 (HSV-1) US3 gene is a multifunctional serine-threonine protein kinase that can block apoptosis induced by proapoptotic cellular proteins, exogenous agents, or replication-defective viruses. Earlier studies showed that the U S 3 kinase activates and...
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Published in | Journal of virology Vol. 80; no. 7; pp. 3341 - 3348 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
01.04.2006
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Online Access | Get full text |
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Summary: | ABSTRACT
The product of the herpes simplex virus 1 (HSV-1) US3 gene is a multifunctional serine-threonine protein kinase that can block apoptosis induced by proapoptotic cellular proteins, exogenous agents, or replication-defective viruses. Earlier studies showed that the U
S
3 kinase activates and functionally overlaps cellular protein kinase A (PKA). In this study we examined the status of phosphatidylinositol 3-kinase [PI(3)K] and of its effector, protein kinase B/Akt (PKB/Akt), a component of a major pathway of mammalian antiapoptotic signaling systems. We report the following. (i) Infection of target cells with HSV-1 induces transient phosphorylation of serine 473 of PKB/Akt early in infection, with a mechanism that is dependent on PI(3)K. Inhibition of PI(3)K induced apoptosis in mock-infected or ΔU
S
3 mutant-virus-infected but not in wild-type-virus-infected cells and reduced the accumulation of specific viral gene products, including the U
S
3 protein kinase, but had a marginal effect on virus yields. (ii) At later times after infection, the total amounts of PKB/Akt decreased and phosphorylated PKB/Akt forms disappeared in a U
S
3-dependent and protein phosphatase 2A-independent manner. (iii) Activation of PKA by forskolin did not mediate significant dephosphorylation of PKB/Akt. Our results are consistent with the model that PKB/Akt is activated early in infection and acts to block apoptosis in infected cells prior to the accumulation of U
S
3 protein kinase and that it persists and continues to function as an antiapoptotic protein in the absence of U
S
3 but becomes redundant or even inimical once U
S
3 protein kinase accumulates in effective amounts. |
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ISSN: | 0022-538X 1098-5514 |
DOI: | 10.1128/JVI.80.7.3341-3348.2006 |