Viral Infection or IFN-α Alters Mitotic Spindle Orientation by Modulating Pericentrin Levels.

Autor:	McDougall WM; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA., Perreira JM; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA., Hung HF; Cell Biology Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda, Bethesda, MD 20814, USA., Vertii A; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA., Xiaofei E; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA., Zimmerman W; Program in Molecular Medicine University of Massachusetts Medical School, Worcester, MA 01605, USA., Kowalik TF; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA., Doxsey S; Program in Molecular Medicine University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: stephen.doxsey@umassmed.edu., Brass AL; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA; Gastroenterology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Peak Gastroenterology Associates, Colorado Springs, CO 80907, USA. Electronic address: abraham.brass@umassmed.edu.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2019 Feb 22; Vol. 12, pp. 270-279. Date of Electronic Publication: 2019 Jan 21.
DOI:	10.1016/j.isci.2019.01.025
Abstrakt:	Congenital microcephaly occurs in utero during Zika virus (ZIKV) infection. The single-gene disorder, Majewski osteodysplastic primordial dwarfism type II (MOPDII), also leads to microcephaly and is concomitant with a decrease in the centrosomal protein, pericentrin (PCNT). This protein is a known contributor of mitotic spindle misorientation and ultimately, microcephaly. Similar to MOPDII, either viral infection or interferon (IFN)-α exposure reduced PCNT levels at the mitotic spindle poles. We unexpectedly found that infection of cells with any one of a diverse set of viruses, such as ZIKV, dengue virus, cytomegalovirus, influenza A virus, or hepatitis B virus, or treatment of cells with the anti-viral cytokine, IFN-α, produced mitotic spindle misorientation. These findings demonstrate a related mechanism for the development of microcephaly in viral infection, the host's antiviral IFN response, and primordial dwarfism. (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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