MxB is an interferon-induced restriction factor of human herpesviruses

Michel Crameri, Michael Bauer, Nicole Caduff, Raphael Walker, Fiona Steiner, Francesca D. Franzoso, Cornelia Gujer, Karin Boucke, Talissa Kucera, Andrea Zbinden, Christian Münz, Cornel Fraefel, Urs F. Greber and Jovan Pavlovic ()
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Michel Crameri: University of Zurich
Michael Bauer: Life Science Zurich Graduate School
Nicole Caduff: Life Science Zurich Graduate School
Raphael Walker: University of Zurich
Fiona Steiner: University of Zurich
Francesca D. Franzoso: University of Zurich
Cornelia Gujer: University of Zurich
Karin Boucke: University of Zurich
Talissa Kucera: University of Zurich
Andrea Zbinden: University of Zurich
Christian Münz: University of Zurich
Cornel Fraefel: University of Zurich
Urs F. Greber: University of Zurich
Jovan Pavlovic: University of Zurich

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract The type I interferon (IFN) system plays an important role in controlling herpesvirus infections, but it is unclear which IFN-mediated effectors interfere with herpesvirus replication. Here we report that human myxovirus resistance protein B (MxB, also designated Mx2) is a potent human herpesvirus restriction factor in the context of IFN. We demonstrate that ectopic MxB expression restricts a range of herpesviruses from the Alphaherpesvirinae and Gammaherpesvirinae, including herpes simplex virus 1 and 2 (HSV-1 and HSV-2), and Kaposi’s sarcoma-associated herpesvirus (KSHV). MxB restriction of HSV-1 and HSV-2 requires GTPase function, in contrast to restriction of lentiviruses. MxB inhibits the delivery of incoming HSV-1 DNA to the nucleus and the appearance of empty capsids, but not the capsid delivery to the cytoplasm or tegument dissociation from the capsid. Our study identifies MxB as a potent pan-herpesvirus restriction factor which blocks the uncoating of viral DNA from the incoming viral capsid.

Date: 2018
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DOI: 10.1038/s41467-018-04379-2

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