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
Affiliations
William M. McDougall
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA
Jill M. Perreira
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA
Hui-Fang Hung
Cell Biology Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda, Bethesda, MD 20814, USA
Anastassiia Vertii
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA
E. Xiaofei
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA
Wendy Zimmerman
Program in Molecular Medicine University of Massachusetts Medical School, Worcester, MA 01605, USA
Timothy F. Kowalik
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA
Stephen Doxsey
Program in Molecular Medicine University of Massachusetts Medical School, Worcester, MA 01605, USA; Corresponding author
Abraham L. Brass
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; Corresponding author
Summary: 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. : Biological Sciences; Pathophysiology; Virology; Cell Biology Subject Areas: Biological Sciences, Pathophysiology, Virology, Cell Biology
