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

Abstract

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.

Cellular Processes Caused by Human Herpesviruses Infection

“…Studies using time-lapse microscopy have shown that HSV-1 undergoes rapid axonal flow in both directions [29,30]. After the nucleocapsid is transported to the surrounding area of the nucleus, it can interact with the nuclear pore complex, and then dsDNA is injected into the nucleus through the nuclear pore [31]. Subsequently, the nucleocapsid is transported towards the nucleus via microtubules.…”

Cellular Processes Induced by HSV-1 Infections in Vestibular Neuritis

“…After the nucleocapsid is transported to the surrounding area of the nucleus, it can interact with the nuclear pore complex, and then, dsDNA is injected into the nucleus through the nuclear pore [ 39 ]. DNA viruses, such as herpesviruses, replicate in specific inclusions within the nucleus.…”

Getting on the right track: Interactions between viruses and the cytoskeletal motor proteins

“… 110 After binding to the cell surface, the HSV envelope fuses with the host plasma membrane, delivering the unenveloped virus, that is, the tegumented capsid, into the cytoplasm 111 . After losing the tegument, the capsid is transported into the nucleus, 112 where transcription and replication take place 113 . The newly assembled capsids are transported from the nucleus into the cytoplasm, in which they acquire the tegument and the envelope at the Golgi, before being transported toward the cell periphery for exit and spread 114,115 …”