BST-2 mediated restriction of simian-human immunodeficiency virus

Virology. 2010 Oct 25;406(2):312-21. doi: 10.1016/j.virol.2010.07.021. Epub 2010 Aug 13.

Abstract

Pathogenic simian-human immunodeficiency viruses (SHIV) contain HIV-1 Vpu and SIV Nef, both shown to counteract BST-2 (HM1.24; CD317; tetherin) inhibition of virus release in a species-specific manner. We show that human and pig-tailed BST-2 (ptBST-2) restrict SHIV. We found that sequential "humanization" of the transmembrane domain (TMD) of the pig-tailed BST-2 (ptBST-2) protein resulted in a fluctuation in sensitivity to HIV-1 Vpu. Our results also show that the length of the TMD in human and ptBST-2 proteins is important for BST-2 restriction and susceptibility to Vpu. Taken together, our results emphasize the importance of tertiary structure in BST-2 antagonism and suggests that the HIV-1 Vpu transmembrane domain may have additional functions in vivo unrelated to BST-2 antagonism.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / chemistry
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Cell Line
  • GPI-Linked Proteins
  • Gene Products, nef / genetics
  • Gene Products, nef / metabolism
  • HIV Infections / metabolism*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Human Immunodeficiency Virus Proteins / genetics
  • Human Immunodeficiency Virus Proteins / metabolism
  • Humans
  • Macaca mulatta
  • Macaca nemestrina
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Reassortant Viruses / genetics
  • Reassortant Viruses / physiology*
  • Sequence Alignment
  • Simian Acquired Immunodeficiency Syndrome / metabolism
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / physiology*
  • Viral Regulatory and Accessory Proteins / genetics
  • Viral Regulatory and Accessory Proteins / metabolism

Substances

  • Antigens, CD
  • BST2 protein, human
  • GPI-Linked Proteins
  • Gene Products, nef
  • Human Immunodeficiency Virus Proteins
  • Membrane Glycoproteins
  • Viral Regulatory and Accessory Proteins
  • vpu protein, Human immunodeficiency virus 1