Surface CD4 expression modulated by a cellular factor induced by HIV type 1 infection.
Human immunodeficiency virus type 1 (HIV-1) alters gene expression in infected cells, leading to cellular dysfunction. We uncovered a number of host cell genes that are modulated in both CD4(+) T cell lines and primary CD4(+) T lymphocytes infected with HIV-1, using high-density oligonucleotide probe microarray technology. We focused on one gene in particular, nuclear factor I-B2 (NFI-B2), because of its high level of expression. NFI-B2 is a member of the nuclear factor I family of nuclear proteins, which are known to be involved in viral and cellular transcription. To better understand the role of NFI-B2 during HIV-1 infection, we generated a Jurkat T cell line that constitutively expressed NFI-B2. After infection with HIV-1, these cells produced fewer viruses because of a downregulation of surface CD4 expression. The surface expression of the coreceptor, CXCR4, remained unchanged. Furthermore, levels of CD4 mRNA were reduced in NFI-B2-producing cells, suggesting that expression of NFI-B2 impairs CD4 transcription. Modulation of NFI-B2 by HIV-1 may represent yet another mechanism by which HIV infection reduces cell surface expression of CD4.
Sheeter
Dennis
D
Department of Medicine, University of California San Diego, La Jolla, California 92093-0679, USA.
Du
Pinyi
P
Rought
Steffney
S
Richman
Douglas
D
Corbeil
Jacques
J
D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D019169:Jurkat Cells; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human