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Abstract
Vesicle-mediated nucleocytoplasmic transport is a nuclear pore-independent mechanism for the nuclear export of macromolecular complexes, but the molecular basis for this transport remains largely unknown. Here we show that endosomal sorting complex required for transport-III (ESCRT-III) is recruited to the inner nuclear membrane (INM) during the nuclear export of herpes simplex virus 1 (HSV-1). Scission during HSV-1 budding through the INM is prevented by depletion of ESCRT-III proteins. Interestingly, in uninfected human cells, the depletion of ESCRT-III proteins induces aberrant INM proliferation. Our results show that HSV-1 expropriates the ESCRT-III machinery in infected cells for scission of the INM to produce vesicles containing progeny virus nucleocapsids. In uninfected cells, ESCRT-III regulates INM integrity by downregulating excess INM.
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Details
1 Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan; Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan
2 Microscope Core Laboratory, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan
3 Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan; Graduate School of Science, Hiroshima University, Higashi-Hiroshima, Hiroshima, Japan
4 Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan