Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-infected cells in a manner dependent on both UL34 and US3.
Cells infected with wild-type herpes simplex virus type 1 (HSV-1) show disruption of the organization of the nuclear lamina that underlies the nuclear envelope. This disruption is reflected in changes in the localization and phosphorylation of lamin proteins. Here, we show that HSV-1 infection causes relocalization of the LEM domain protein emerin. In cells infected with wild-type virus, emerin becomes more mobile in the nuclear membrane, and in cells infected with viruses that fail to express UL34 protein (pUL34) and US3 protein (pUS3), emerin no longer colocalizes with lamins, suggesting that infection causes a loss of connection between emerin and the lamina. Infection causes hyperphosphorylation of emerin in a manner dependent upon both pUL34 and pUS3. Some emerin hyperphosphorylation can be inhibited by the protein kinase Cdelta (PKCdelta) inhibitor rottlerin. Emerin and pUL34 interact physically, as shown by pull-down and coimmunoprecipitation assays. Emerin expression is not, however, necessary for infection, since virus growth is not impaired in cells derived from emerin-null transgenic mice. The results suggest a model in which pUS3 and PKCdelta that has been recruited by pUL34 hyperphosphorylate emerin, leading to disruption of its connections with lamin proteins and contributing to the disruption of the nuclear lamina. Changes in emerin localization, nuclear shape, and lamin organization characteristic of cells infected with wild-type HSV-1 also occur in cells infected with recombinant virus that does not make viral capsids, suggesting that these changes occur independently of capsid envelopment.
Leach
Natalie
N
Department of Microbiology, The University of Iowa, 3-432 Bowen Science Building, Iowa City, IA 52242, USA.
Bjerke
Susan L
SL
Christensen
Desire K
DK
Bouchard
Jacques M
JM
Mou
Fan
F
Park
Richard
R
Baines
Joel
J
Haraguchi
Tokuko
T
Roller
Richard J
RJ
D000595:Amino Acid Sequence; D002213:Capsid / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D006561:Herpes Simplex / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000737:chemistry / Q000378:metabolism; D034881:Nuclear Lamina / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism*; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D008565:Membrane Proteins; D009687:Nuclear Proteins; C403420:UL34 protein, Human herpesvirus 1; D014764:Viral Proteins; C092710:emerin; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases; C095207:US3 protein, Human herpesvirus 1; D051745:Protein Kinase C-delta