The Portal Vertex of KSHV Promotes Docking of Capsids at the Nuclear Pores.
Kaposi's sarcoma-associated herpesvirus (KSHV) is a cancer-related herpesvirus. Like other herpesviruses, the KSHV icosahedral capsid includes a portal vertex, composed of 12 protein subunits encoded by open reading frame (ORF) 43, which enables packaging and release of the viral genome into the nucleus through the nuclear pore complex (NPC). Capsid vertex-specific component (CVSC) tegument proteins, which directly mediate docking at the NPCs, are organized on the capsid vertices and are enriched on the portal vertex. Whether and how the portal vertex is selected for docking at the NPC is unknown. Here, we investigated the docking of incoming ORF43-null KSHV capsids at the NPCs, and describe a significantly lower fraction of capsids attached to the nuclear envelope compared to wild-type (WT) capsids. Like WT capsids, nuclear envelope-associated ORF43-null capsids co-localized with different nucleoporins (Nups) and did not detach upon salt treatment. Inhibition of nuclear export did not alter WT capsid docking. As ORF43-null capsids exhibit lower extent of association with the NPCs, we conclude that although not essential, the portal has a role in mediating the interaction of the CVSC proteins with Nups, and suggest a model whereby WT capsids can dock at the nuclear envelope through a non-portal penton vertex, resulting in an infection 'dead end'.
['Dünn-Kittenplon|Daniela|D|', 'Ashkenazy-Titelman|Asaf|A|', 'Kalt|Inna|I|', 'Lellouche|Jean-Paul|JP|0000-0002-0177-8151', 'Shav-Tal|Yaron|Y|0000-0002-8017-948X', 'Sarid|Ronit|R|0000-0001-8658-0453']
D002213:Capsid D036022:Capsid Proteins D045744:Cell Line, Tumor D020285:Cryoelectron Microscopy D004279:DNA, Viral D016679:Genome, Viral D019288:Herpesvirus 8, Human D006801:Humans D008958:Models, Molecular D062105:Molecular Docking Simulation D022022:Nuclear Pore D016366:Open Reading Frames D019065:Virus Assembly
portal nuclear pore complex (NPC) capsid vertex-specific component (CVSC) Kaposi’s sarcoma-associated herpesvirus (KSHV) open reading frame 43 (ORF43)