Herpes simplex virus 2 UL13 protein kinase disrupts nuclear lamins

Virology. 2009 Sep 15;392(1):137-47. doi: 10.1016/j.virol.2009.06.051. Epub 2009 Jul 28.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Active Transport, Cell Nucleus
  • Base Sequence
  • Binding Sites
  • DNA Primers / genetics
  • DNA, Viral / genetics
  • HeLa Cells
  • Herpesvirus 2, Human / enzymology*
  • Herpesvirus 2, Human / genetics
  • Herpesvirus 2, Human / pathogenicity*
  • Humans
  • Lamin Type A / chemistry
  • Lamin Type A / genetics
  • Lamin Type A / metabolism
  • Lamin Type B / chemistry
  • Lamin Type B / genetics
  • Lamin Type B / metabolism
  • Lamins / chemistry
  • Lamins / genetics
  • Lamins / metabolism*
  • Nuclear Lamina / metabolism*
  • Nuclear Lamina / virology*
  • Phosphorylation
  • Protein Conformation
  • Protein Kinases / genetics
  • Protein Kinases / physiology*
  • Protein Structure, Tertiary
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transfection

Substances

  • DNA Primers
  • DNA, Viral
  • LMNA protein, human
  • Lamin Type A
  • Lamin Type B
  • Lamins
  • Recombinant Proteins
  • lamin B1
  • Protein Kinases
  • UL13 protein, Simplexvirus