Gene expression profile of HIV-1 Tat expressing cells: a close interplay between proliferative and differentiation signals

Cynthia de la Fuente² , Francisco Santiago² , Longwen Deng² , Carolyne Eadie² , Irene Zilberman² , Kylene Kehn² , Anil Maddukuri² , Shanese Baylor² , Kaili Wu² , Chee Gun Lee¹ , Anne Pumfery² and Fatah Kashanchi²

¹Department of Biochemistry and Molecular Biology UMDNJ-New Jersey Medical School Newark, NJ 07103, USA

²Department of Biochemistry and Molecular Biology George Washington University School of Medicine Washington DC, 20037, USA

author email corresponding author email

BMC Biochemistry 2002, 3:14doi:10.1186/1471-2091-3-14


Published:	10 June 2002

Abstract

Background

Expression profiling holds great promise for rapid host genome functional analysis. It is plausible that host expression profiling in an infection could serve as a universal phenotype in virally infected cells. Here, we describe the effect of one of the most critical viral activators, Tat, in HIV-1 infected and Tat expressing cells. We utilized microarray analysis from uninfected, latently HIV-1 infected cells, as well as cells that express Tat, to decipher some of the cellular changes associated with this viral activator.

Results

Utilizing uninfected, HIV-1 latently infected cells, and Tat expressing cells, we observed that most of the cellular host genes in Tat expressing cells were down-regulated. The down-regulation in Tat expressing cells is most apparent on cellular receptors that have intrinsic receptor tyrosine kinase (RTK) activity and signal transduction members that mediate RTK function, including Ras-Raf-MEK pathway. Co-activators of transcription, such as p300/CBP and SRC-1, which mediate gene expression related to hormone receptor genes, were also found to be down-regulated. Down-regulation of receptors may allow latent HIV-1 infected cells to either hide from the immune system or avoid extracellular differentiation signals. Some of the genes that were up-regulated included co-receptors for HIV-1 entry, translation machinery, and cell cycle regulatory proteins.

Conclusions

We have demonstrated, through a microarray approach, that HIV-1 Tat is able to regulate many cellular genes that are involved in cell signaling, translation and ultimately control the host proliferative and differentiation signals.