Craig B. Woda

Herpes simplex virus triggers activation of calcium-signaling pathways

The cellular pathways required for herpes simplex virus (HSV) invasion have not been defined. To test the hypothesis that HSV entry triggers activation of Ca2+-signaling pathways, the effects on intracellular calcium concentration ([Ca2+]i) after exposure of cells to HSV were examined. Exposure to virus results in a rapid and transient increase in [Ca2+]i. Pretreatment of cells with pharmacological agents that block release of inositol 1,4,5-triphosphate (IP3)–sensitive endoplasmic reticulum stores abrogates the response. Moreover, treatment of cells with these pharmacological agents inhibits HSV infection and prevents focal adhesion kinase (FAK) phosphorylation, which occurs within 5 min after viral infection. Viruses deleted in glycoprotein L or glycoprotein D, which bind but do not penetrate, fail to induce a [Ca2+]i response or trigger FAK phosphorylation. Together, these results support a model for HSV infection that requires activation of IP3-responsive Ca2+-signaling pathways and that is associated with FAK phosphorylation. Defining the pathway of viral invasion may lead to new targets for anti-viral therapy.

Development of Function in the Metanephric Kidney

Publisher Summary This chapter focuses on characterizing the normal functional development of the metanephric kidney. Although the bulk of the fundamental knowledge about these processes derives from investigations in animal models, available data from studies in the human fetus and neonate are also discussed in the chapter. In animal models used to study ontogeny of renal function, nephronogenesis is complete before term birth in sheep and guinea pig. The fetal sheep provides an excellent model of human nephronogenesis as its program of renal development closely parallels that of the human. Nephronogenesis continues for ∼1 week after term birth in rat and mouse and ∼2 weeks in rabbit and dog. Thus, functional analyses of the differentiating kidney in these latter species are complicated by the concurrent presence of nephrons in diverse stages of differentiation. Furthermore, physiologic, biochemical, and enzymatic maturation of newly formed nephrons in all species may lag behind anatomic maturation by weeks or months. A comparison of the developmental changes in renal function among various species is best considered not as pre- or postnatal events but in terms of their relationship to the completion of nephrogenesis.