Department of Microbiology and Physiological Systems; Department of Molecular, Cell and Cancer Biology; Program in Molecular Medicine
Amino Acids, Peptides, and Proteins | Biological Factors | Cell Biology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Immunology and Infectious Disease | Virology | Virus Diseases | Viruses
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)-alpha 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-alpha, 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, Cell Biology, Pathophysiology, Virology
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Copyright 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
iScience. 2019 Feb 22;12:270-279. doi: 10.1016/j.isci.2019.01.025. Epub 2019 Jan 21. Link to article on publisher's site
McDougall WM, Perreira J, Hung H, Vertii A, Xiaofei E, Zimmerman W, Kowalik TF, Doxsey SJ, Brass AL. (2019). Viral Infection or IFN-alpha Alters Mitotic Spindle Orientation by Modulating Pericentrin Levels. Open Access Articles. https://doi.org/10.1016/j.isci.2019.01.025. Retrieved from https://escholarship.umassmed.edu/oapubs/3732
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Amino Acids, Peptides, and Proteins Commons, Biological Factors Commons, Cell Biology Commons, Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons, Immunology and Infectious Disease Commons, Virology Commons, Virus Diseases Commons, Viruses Commons