The inner-nuclear-envelope protein emerin regulates HIV-1 infectivity

Nature. 2006 Jun 1;441(7093):641-5. doi: 10.1038/nature04682. Epub 2006 May 7.

Abstract

Primate lentiviruses such as human immunodeficiency type 1 (HIV-1) have the capacity to infect non-dividing cells such as tissue macrophages. In the process, viral complementary DNA traverses the nuclear envelope to integrate within chromatin. Given the intimate association between chromatin and the nuclear envelope, we examined whether HIV-1 appropriates nuclear envelope components during infection. Here we show that emerin, an integral inner-nuclear-envelope protein, is necessary for HIV-1 infection. Infection of primary macrophages lacking emerin was abortive in that viral cDNA localized to the nucleus but integration into chromatin was inefficient, and conversion of viral cDNA to non-functional episomal cDNA increased. HIV-1 cDNA associated with emerin in vivo, and the interaction of viral cDNA with chromatin was dependent on emerin. Barrier-to-autointegration factor (BAF), the LEM (LAP, emerin, MAN) binding partner of emerin, was required for the association of viral cDNA with emerin and for the ability of emerin to support virus infection. Therefore emerin, which bridges the interface between the inner nuclear envelope and chromatin, may be necessary for chromatin engagement by viral cDNA before integration.

Publication types

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

MeSH terms

  • Cells, Cultured
  • Chromatin / genetics
  • Chromatin / metabolism
  • DNA, Complementary / genetics
  • DNA, Complementary / metabolism
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • HIV Integrase / metabolism
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • HeLa Cells
  • Humans
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Macrophages / virology*
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • RNA Interference
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Thymopoietins / deficiency
  • Thymopoietins / genetics
  • Thymopoietins / metabolism*
  • Virus Integration / physiology*

Substances

  • BANF1 protein, human
  • Chromatin
  • DNA, Complementary
  • DNA, Viral
  • DNA-Binding Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • RNA, Small Interfering
  • Thymopoietins
  • emerin
  • HIV Integrase