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

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)-? 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-?, 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.

SUBMITTER: McDougall WM 

PROVIDER: S-EPMC6360249 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

McDougall William M WM   Perreira Jill M JM   Hung Hui-Fang HF   Vertii Anastassiia A   Xiaofei E E   Zimmerman Wendy W   Kowalik Timothy F TF   Doxsey Stephen S   Brass Abraham L AL  

iScience 20190121

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  ...[more]