Herpes simplex virus 1 U(L)31 and U(L)34 gene products promote the late maturation of viral replication compartments to the nuclear periphery.
Herpes simplex virus 1 (HSV-1) forms replication compartments (RCs), domains in which viral DNA replication, late-gene transcription, and encapsidation take place, in the host cell nucleus. The formation of these domains leads to compression and marginalization of host cell chromatin, which forms a dense layer surrounding the viral RCs and constitutes a potential barrier to viral nuclear egress or primary envelopment at the inner nuclear membrane. Surrounding the chromatin layer is the nuclear lamina, a further host cell barrier to egress. In this study, we describe an additional phase in RC maturation that involves disruption of the host chromatin and nuclear lamina so that the RC can approach the nuclear envelope. During this phase, the structure of the chromatin layer is altered so that it no longer forms a continuous layer around the RCs but instead is fragmented, forming islands between which RCs extend to reach the nuclear periphery. Coincident with these changes, the nuclear lamina components lamin A/C and lamin-associated protein 2 appear to be redistributed via a mechanism involving the U(L)31 and U(L)34 gene products. Viruses in which the U(L)31 or U(L)34 gene has been deleted are unable to undergo this phase of chromatin reorganization and lamina alterations and instead form RCs which are bounded by an intact host cell chromatin layer and nuclear lamina. We postulate that these defects in chromatin restructuring and lamina reorganization explain the previously documented growth defects of these mutant viruses.
Simpson-Holley
Martha
M
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115, USA.
Baines
Joel
J
Roller
Richard
R
Knipe
David M
DM
D000818:Animals; D002467:Cell Nucleus / Q000821:virology*; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000737:chemistry; D004268:DNA-Binding Proteins; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D034881:Nuclear Lamina / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology*; D014709:Vero Cells; D014764:Viral Proteins / Q000032:analysis / Q000502:physiology*; D014779:Virus Replication
D002843:Chromatin; D004268:DNA-Binding Proteins; C045462:ICP8 protein, Simplexvirus; D009687:Nuclear Proteins; C108721:UL31 protein, Human herpesvirus 1; C403420:UL34 protein, Human herpesvirus 1; D014764:Viral Proteins