Role of HSV-1 Capsid Vertex-Specific Component (CVSC) and Viral Terminal DNA in Capsid Docking at the Nuclear Pore.

José Ramon Villanueva-Valencia, Efthymios Tsimtsirakis, Alex Evilevitch

Viruses 2021 Dec 15

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Penetration of the viral genome into a host cell nucleus is critical for initiation of viral replication for most DNA viruses and a few RNA viruses. For herpesviruses, viral DNA ejection into a nucleus occurs when the capsid docks at the nuclear pore complex (NPC) basket with the correct orientation of the unique capsid portal vertex. It has been shown that capsid vertex-specific component (CVSC) proteins, which are located at the twelve vertices of the human herpes simplex virus type 1 (HSV-1) capsid, interact with nucleoporins (Nups) of NPCs. However, it remained unclear whether CVSC proteins determine capsid-to-NPC binding. Furthermore, it has been speculated that terminal DNA adjacent to the portal complex of DNA-filled C-capsids forms a structural motif with the portal cap (which retains DNA in the capsid), which mediates capsid-NPC binding. We demonstrate that terminal viral DNA adjacent to the portal proteins does not present a structural element required for capsid-NPC binding. Our data also show that level of CVSC proteins on the HSV-1 capsid affects level of NPC binding. To elucidate the capsid-binding process, we use an isolated, reconstituted cell nucleus system that recapitulates capsid-nucleus binding in vivo without interference from trafficking kinetics of capsids moving toward the nucleus. This allows binding of non-infectious capsid maturation intermediates with varying levels of vertex-specific components. This experimental system provides a platform for investigating virus-host interaction at the nuclear membrane.

Citation

José Ramon Villanueva-Valencia, Efthymios Tsimtsirakis, Alex Evilevitch. Role of HSV-1 Capsid Vertex-Specific Component (CVSC) and Viral Terminal DNA in Capsid Docking at the Nuclear Pore. Viruses. 2021 Dec 15;13(12)