Gene expression profile of HIV-1 Tat expressing cells: a close interplay between proliferative and differentiation signals.
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.
de la Fuente
Cynthia
C
Department of Biochemistry and Molecular Biology George Washington University School of Medicine Washington DC 20037, USA. bcmfxk@gwumc.edu
Santiago
Francisco
F
Deng
Longwen
L
Eadie
Carolyne
C
Zilberman
Irene
I
Kehn
Kylene
K
Maddukuri
Anil
A
Baylor
Shanese
S
Wu
Kaili
K
Lee
Chee Gun
CG
Pumfery
Anne
A
Kashanchi
Fatah
F
D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002843:Chromatin / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000235:genetics; D015696:Gene Products, tat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology; D006801:Humans; D014176:Protein Biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D013947:Thymosin / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured; D054322:tat Gene Products, Human Immunodeficiency Virus
D002843:Chromatin; D015696:Gene Products, tat; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D013947:Thymosin