Herpes simplex virus 2 UL13 protein kinase disrupts nuclear lamins.
Herpesviruses must cross the inner nuclear membrane and underlying lamina to exit the nucleus. HSV-1 US3 and PKC can phosphorylate lamins and induce their dispersion but do not elicit all of the phosphorylated lamin species produced during infection. UL13 is a serine threonine protein kinase conserved among many herpesviruses. HSV-1 UL13 phosphorylates US3 and thereby controls UL31 and UL34 nuclear rim localization, indicating a role in nuclear egress. Here, we report that HSV-2 UL13 alone induced conformational changes in lamins A and C and redistributed lamin B1 from the nuclear rim to intranuclear granular structures. HSV-2 UL13 directly phosphorylated lamins A, C, and B1 in vitro, and the lamin A1 tail domain. HSV-2 infection recapitulated the lamin alterations seen upon expression of UL13 alone, and other alterations were also observed, indicating that additional viral and/or cellular proteins cooperate with UL13 to alter lamins during HSV-2 infection to allow nuclear egress.
Cano-Monreal
Gina L
GL
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1100 South Grand Blvd., St. Louis, MO 63104, USA.
Wylie
Kristine M
KM
Cao
Feng
F
Tavis
John E
JE
Morrison
Lynda A
LA
D021581:Active Transport, Cell Nucleus; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D006367:HeLa Cells; D018258:Herpesvirus 2, Human / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D034904:Lamin Type A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D034921:Lamin Type B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D034882:Lamins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034881:Nuclear Lamina / Q000378:metabolism* / Q000821:virology*; D010766:Phosphorylation; D011487:Protein Conformation; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D017931:DNA Primers; D004279:DNA, Viral; C494847:LMNA protein, human; D034904:Lamin Type A; D034921:Lamin Type B; D034882:Lamins; D011994:Recombinant Proteins; D011494:Protein Kinases; C082380:UL13 protein, Simplexvirus