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

William M McDougall; Jill M Perreira; Hui-Fang Hung; Anastassiia Vertii; E Xiaofei; Wendy Zimmerman; Timothy F Kowalik; Stephen Doxsey; Abraham L Brass

doi:10.1016/j.isci.2019.01.025

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

iScience. 2019 Feb 22:12:270-279. doi: 10.1016/j.isci.2019.01.025. Epub 2019 Jan 21.

Authors

William M McDougall¹, Jill M Perreira¹, Hui-Fang Hung², Anastassiia Vertii³, E Xiaofei¹, Wendy Zimmerman⁴, Timothy F Kowalik¹, Stephen Doxsey⁵, Abraham L Brass⁶

Affiliations

¹ Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA.
² Cell Biology Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda, Bethesda, MD 20814, USA.
³ Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
⁴ Program in Molecular Medicine University of Massachusetts Medical School, Worcester, MA 01605, USA.
⁵ Program in Molecular Medicine University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: stephen.doxsey@umassmed.edu.
⁶ 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.

Abstract

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.

Keywords: Biological Sciences; Cell Biology; Pathophysiology; Virology.