Surface CD4 Expression Modulated by a Cellular Factor Induced by HIV Type 1 Infection

Abstract

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.

Genome-wide genetic associations with IFNγ response to smallpox vaccine

“…NFIB is a member of the Nuclear Factor I family of DNA binding proteins that regulate the transcription of multiple cellular signaling pathways (insulin, TGF-β, TNFa, steroid hormones, vitamins), and are essential for the replication of many viruses (Gronostajski 2000). Interestingly, overexpression of NFIB2 leads to downregulation of surface CD4 expression (Sheeter et al 2003). One potential mechanism behind the genetic association between NFIB and IFNγ response might be the control of CD4 expression and concomitant up/down-regulation of T helper responses upon antigen exposure.…”

In vivo CXCR4 expression, lymphoid cell phenotype, and feline immunodeficiency virus infection

“…In these studies only marginal decreases in proviral loads were seen in cats following AMD3100 treatment versus nearly complete inhibition of virus in PBMC in vitro. While in vitro studies with FIV (Willett et al, 2003) and HIV (Sheeter et al, 2003) have demonstrated no effect of lentiviral infection on X4 expression, clinical data exist suggesting downregulation in vivo (Nicholson et al, 2001, Ruibal-Ares et al, 2004, Shalekoff et al, 2001. Thus, while attempts were made to reduce temporal variability in X4 expression in the present study via in vitro CXCR4 upregulation, it is possible that post-infection down regulation of X4 expression may have occurred.…”

Microarray analysis of differentially expressed genes in cells resistant to HIV-1

“…However, other studies suggested that IL-9 receptor interacts with Tip60 protein-a novel mediator of Tat-dependent trans- activation based on its histone acetylotransferase activity [32]. Two of the up-regulated genes, CD80 antigen and nuclear factor I, were connected to cellular resistance to virus via down-regulation of surface CD4 receptor or increased production of ␤-chemokines [15,16,33]. It has been reported that the ligation of CD80 antigen to CD28 molecule up-regulates the expression of several genes including IL-2 and CD40 ligand (CD40L) [33].…”

“…NFI is a member of a large family of nuclear proteins which are known to be involved in viral and cellular transcription. The over-expression of NFI-B2 in Jurkat T cell line resulted in inhibition of HIV-1 infection through down-regulation of surface CD4 expression [15], raising the possibility that activation of NFI expression plays a role in the HIV-1 resistance of HRF(+) cells.…”

“…Three of the down-modulated transcription factors are required for HIV-1 LTR promoter activity. Among the up-regulated genes, three are important for virus life cycle and their elevated expression was associated with cellular resistance to HIV-1 [14][15][16]. Two of the most up-regulated genes one as potent inhibitor of transcription and the other a transcript of unknown function were selected to further studies by RT-PCR and Northern blot.…”