Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 24, Pages 10187-10192Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0703790104
Keywords
egress; nuclear envelope; deenvelopment; perinuclear space
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Funding
- NEI NIH HHS [EY 11245, R01 EY011245] Funding Source: Medline
- NIAID NIH HHS [R37 AI018289, AI 56045, R01 AI018289, AI 73996, AI 18289, R01 AI041478, AI 41478, R21 AI056045, R01 AI056045] Funding Source: Medline
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Herpesviruses must traverse the nuclear envelope to gain access to the cytoplasm and, ultimately, to exit cells. It is believed that herpesvirus nucleocapsids enter the perinuclear space by budding through the inner nuclear membrane (NM). To reach the cytoplasm these enveloped particles must fuse with the outer NM and the unenveloped capsids then acquire a second envelope in the trans-Golgi network. Little is known about the process by which herpesviruses virions fuse with the outer NM. Here we show that a herpes simplex virus (HSV) mutant lacking both the two putative fusion glycoproteins gB and gH failed to cross the nuclear envelope. Enveloped virions accumulated in the perinuclear space or in membrane vesicles that bulged into the nucleoplasm (herniations). By contrast, mutants lacking just gB or gH showed only minor or no defects in nuclear egress. We concluded that either HSV gB or gH can promote fusion between the virion envelope and the outer NM. It is noteworthy that fusion associated with HSV entry requires the cooperative action of both gB and gH, suggesting that the two types of fusion (egress versus entry) are dissimilar processes.
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