Visualization of Tegument-Capsid Interactions and DNA in Intact Herpes Simplex Virus Type 1 Virions

Abstract

Herpes simplex virus type 1 virions were examined by electron cryomicroscopy, allowing the three-dimensional structure of the infectious particle to be visualized for the first time. The capsid shell is identical to that of B-capsids purified from the host cell nucleus, with the exception of the penton channel, which is closed. The double-stranded DNA genome is organized as regularly spaced (∼26 Å) concentric layers inside the capsid. This pattern suggests a spool model for DNA packaging, similar to that for some bacteriophages. The bulk of the tegument is not icosahedrally ordered. However, a small portion appears as filamentous structures around the pentons, interacting extensively with the capsid. Their locations and interactions suggest possible roles for the tegument proteins in regulating DNA transport through the penton channel and binding to cellular transport proteins during viral infection.

Proteolytic Cleavage of VP1-2 Is Required for Release of Herpes Simplex Virus 1 DNA into the Nucleus

“…(ii) HSV-1 capsids have been observed in electron micrographs to face nuclear pores with a vertex (33,40). (iii) VP1-2 is very closely associated with capsids (15, 41); more specifically, VP1-2 was suggested to be associated with pentons of the virion capsid, occupying the space between the upper domains of two adjacent penton VP5 subunits (44). Such intimate association between VP1-2 and pentons makes it feasible that the conformation of pentons would be influenced by changes (i.e., proteolytic cleavage) in VP1-2.…”

“…The capsid with associated tegument proteins is released into the cytosol and transported via dynein and microtubule-directed transport toward the nucleus (40). During the transport some tegument proteins, most notably VP16 (2) and virion host shutoff protein (23), the products of U L 48 and U L 41, respectively, are released, whereas some, such as VP1-2, the product of the U L 36 gene, remain associated with the capsid (16,44). Once the capsid arrives at the nuclear pore, viral DNA is rapidly released into the nucleus to enable the expression of its genes.…”

“…VP1-2 plays an essential role in the formation of mature virions, as the deletion of the U L 36 gene leads to the accumulation of DNA-filled, unenveloped capsids in the cytoplasm of infected cells (6). VP1-2 is tightly associated with capsid (15,41), and based on cryoelectron microscopy images it appears that it is localized at the penton structures (44). VP1-2 interacts with a 140-kDa viral protein that binds the a sequence of HSV-1 DNA (5) and is suggested to interact with VP5 (44).…”

“…VP1-2 is tightly associated with capsid (15,41), and based on cryoelectron microscopy images it appears that it is localized at the penton structures (44). VP1-2 interacts with a 140-kDa viral protein that binds the a sequence of HSV-1 DNA (5) and is suggested to interact with VP5 (44). VP1-2 is the largest protein encoded by the U L 36 gene.…”

Herpes Simplex Virus 1 Ubiquitin-Specific Protease UL36 Inhibits Beta Interferon Production by Deubiquitinating TRAF3

“…VP1/2, a large multifunctional protein, plays crucial roles in HSV-1 entry, capsid transport, and virion assembly, formation of mature virions, microtubule transport of capsids, neuroinvasion, pathogenesis, etc. (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). Kattenhorn et al have identified an approximately 500-amino-acid peptide that exhibits unique deubiquitinase (DUB) activity (denoted as UL36USP, for UL36 ubiquitin-specific protease), which is embedded within the N-terminal region of HSV-1 VP1/2 (42).…”