Human cytomegaloviral multifunctional protein kinase pUL97 impairs zebrafish embryonic development and increases mortality

Cazorla-Vázquez S, Steingruber M, Marschall M, Engel F (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 9

Article Number: 7219

Journal Issue: 1

DOI: 10.1038/s41598-019-43649-x

Abstract

Cytomegalovirus is a worldwide-distributed human pathogen, which is the leading cause of congenital virus infection, affecting 0.5 to 2% of live births. To date, it is largely unclear which molecular mechanisms underlie the symptomatic outcomes. This is mainly due to species specificity and limited homology among cytomegalovirus genomes. As it is not possible to infect model organisms with human cytomegalovirus, the aim of this study was to develop a heterologous system allowing in the future the elucidation of the pathological role of individual viral proteins. As a model organism the zebrafish has been chosen due to its ease of manipulation and characterization as well as its large offspring. As cytomegalovirus model protein, pUL97 was characterized because it is multiply involved in virus-host interaction. Here, we show in zebrafish embryos, that (i) pUL97 can be expressed in zebrafish, (ii) increasing pUL97 expression levels quantitatively correlate with both minor and major pathological defects, (iii) pUL97 expression impairs cell cycle progression and induces cell death, (iv) active pUL97, but not an inactive mutant, induces excess mortality, and (v) co-administration of a pUL97 inhibitor reduces embryonic pathology. Collectively, these data indicate the suitability of zebrafish to elucidate the pathological role of human cytomegaloviral proteins.

Authors with CRIS profile

Mirjam Steingruber Institute of Clinical and Molecular Virology Manfred Marschall Lehrstuhl für Klinische und Molekulare Virologie Felix Engel Professur für Experimentelle Nieren- und Kreislaufforschung

How to cite

APA:

Cazorla-Vázquez, S., Steingruber, M., Marschall, M., & Engel, F. (2019). Human cytomegaloviral multifunctional protein kinase pUL97 impairs zebrafish embryonic development and increases mortality. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-43649-x

MLA:

Cazorla-Vázquez, Salvador, et al. "Human cytomegaloviral multifunctional protein kinase pUL97 impairs zebrafish embryonic development and increases mortality." Scientific Reports 9.1 (2019).

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