Comparative molecular genetic analysis of simian and human HIV-1 integrase interactor INI1/SMARCB1/SNF5

Arch Virol. 2015 Dec;160(12):3085-91. doi: 10.1007/s00705-015-2585-x. Epub 2015 Sep 8.

Abstract

Human integrase interactor 1 (INI1/SMARCB1/SNF5) is a chromatin-remodeling molecule that binds to HIV-1 integrase and enhances proviral DNA integration. INI1 is also known as a tumor suppressor gene and has been found to be mutated in several aggressive tumors such as rhabdoid and lymphoid tumors. To study the function of simian INI1, we screened and cloned simian INI1 cDNA from B lymphoma cells of rhesus monkeys using RT-PCR. Sequence analysis showed 23 single nucleotide differences compared to the human ortholog, which, however, did not result in amino acid changes, and the amino acid sequence is therefore 100% conserved between human and simian INI1. Two alternatively spliced isoforms, INI1a and INI1b, were also found in simian INI1. These two isoforms did not show any functional difference in HIV-1 proviral DNA integration and nuclear localization, suggesting that the specificity of simian INI1 would not be a factor preventing HIV-1 infection of a simian host. Nevertheless, INI1b is expressed only in established cancer cell lines such as Jurkat and COS-7 cells, and not in primary cells, suggesting that INIlb could be an indicator of cell transformation.

Keywords: HIV-1; Integrase, integration of provirus; Simian INI1/SMARCB1/SNF5.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Chlorocebus aethiops
  • Chromosomal Proteins, Non-Histone / chemistry*
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cloning, Molecular
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • HIV Infections / genetics
  • HIV Infections / metabolism*
  • HIV Infections / virology
  • HIV Integrase / genetics
  • HIV Integrase / metabolism*
  • HIV-1 / enzymology*
  • HIV-1 / genetics
  • Humans
  • Macaca mulatta / genetics*
  • Macaca mulatta / metabolism
  • Macaca mulatta / virology
  • Molecular Sequence Data
  • Protein Binding
  • SMARCB1 Protein
  • Sequence Alignment
  • Simian Acquired Immunodeficiency Syndrome / genetics
  • Simian Acquired Immunodeficiency Syndrome / metabolism*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / enzymology*
  • Simian Immunodeficiency Virus / genetics
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors
  • HIV Integrase