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Molecular Aspects of Human Cytomegalovirus Diseases pp 384–411Cite as

Activation of Proto-oncogenes and Cell Activation Signals in the Initiation and Progression of Human Cytomegalovirus Infection

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Part of the book series: Frontiers of Virology ((FRVIROLOGY,volume 2))

Summary

Human cytomegalovirus (HCMV) activates cells through a signal cascade that shares components with the activation mechanisms induced by serum or growth factors. Moreover, HCMV infection appears to perturb cellular control of the signal cascade protracting some cellular responses. These cellular responses may be divided into three phases. Immediate early (IE) cellular signals include increased metabolism of phosphoinositides and arachidonic acid and activation of cellular oncogenes fos, jun, and myc. These IE cellular responses appear to result from the interaction of the virus particle with the plasmalemma, since they do not appear to be related to virus infectivity, do not require cellular or viral protein synthesis, occur when virus particles are located at the plasma membrane, and appear to be related to the activity of membrane-associated enzymes. Our preliminary findings suggest that the IE cellular responses are related to initiation and regulation of HCMV IE gene expression. Early cellular responses include increases in the cellular levels of inositol 1,4,5-trisphosphate (IP3), 1,2-diacylglycerol (DG), cyclic nucleotides, release of arachidonic acid (AA), a substantial and protracted increase in cytosolic [Ca2+], and a decrease in Na+/K+ adenosine triphosphatase (ATPase) activity that may be related to changes in intracellular pH. Early cellular responses appear to be related to virus infectivity, ongoing cellular RNA and protein synthesis, and to the development and progression of cytopathology. Ca2+ signals are protracted into the late phase, which is most notably characterized by a sustained increase in Na+/K+ ATPase activity that is presumably related to Na+ entry. As interference with the cellular responses results in substantial reductions in infectious yields of HCMV, it is likely that these cellular changes are related to efficient HCMV replication. Furthermore, the cellular signals provoked by HCMV appear to be related to cell cycle perturbation and induction of chromosome damage.

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Authors and Affiliations

  1. Department of Microbiology, University of Texas Medical Branch, Galveston, TX, 77550, USA

    T. Albrecht, I. Boldogh, M. P. Fons & T. Valyi-Nagy

  2. Department of Microbiology, Medical University of Debrecen, 4012, Debrecen, Hungary

    I. Boldogh

  3. The Wistar Institute, 36th and Spruce Streets, Philadelphia, PA, USA

    T. Valyi-Nagy

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  1. T. Albrecht
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  2. I. Boldogh
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  3. M. P. Fons
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  4. T. Valyi-Nagy
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Editors and Affiliations

  1. Department of Molecular Virology, Faculty of Medicine, Hebrew University of Jerusalem, POB 1172, 910010, Jerusalem, Israel

    Yechiel Becker

  2. Institut für Medizinische Virologie, Universität Heidelberg, Im Neuenheimer Feld 324, W-6900, Heidelberg, Germany

    Gholamreza Darai

  3. Lineberger Comprehensive Cancer Research Center, The University of North Carolina, CB # 7259, Rm. 117, Lineberger Building, 27599-7295, Chapel Hill, NC, USA

    Eng-Shang Huang Ph. D.

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Albrecht, T., Boldogh, I., Fons, M.P., Valyi-Nagy, T. (1993). Activation of Proto-oncogenes and Cell Activation Signals in the Initiation and Progression of Human Cytomegalovirus Infection. In: Becker, Y., Darai, G., Huang, ES. (eds) Molecular Aspects of Human Cytomegalovirus Diseases. Frontiers of Virology, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84850-6_19

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