Therapeutic targets for HIV-1 infection in the host proteome

doi:10.1186/1742-4690-2-20

Retrovirology
Volume 2

Viewing options:

Abstract
Full text
PDF (1.3MB)
Additional files

Associated material:

Related literature:

Articles citing this article
on BioMed Central
on Google Scholar
on ISI Web of Science
on PubMed Central
Other articles by authors
on Google Scholar

Liang WS
Maddukuri A
Teslovich TM
de la Fuente C
Agbottah E
Dadgar S
Kehn K
Hautaniemi S
Pumfery A
Stephan DA
Kashanchi F

on PubMed

Liang WS
Maddukuri A
Teslovich TM
de la Fuente C
Agbottah E
Dadgar S
Kehn K
Hautaniemi S
Pumfery A
Stephan DA
Kashanchi F
Related articles/pages
on Google

on Google Scholar

on PubMed

Tools:

Post to:

Research

Therapeutic targets for HIV-1 infection in the host proteome

Winnie S Liang^*² , Anil Maddukuri^*¹ , Tanya M Teslovich³ , Cynthia de la Fuente¹ , Emmanuel Agbottah¹ , Shabnam Dadgar¹ , Kylene Kehn¹ , Sampsa Hautaniemi⁴ , Anne Pumfery¹ , Dietrich A Stephan² and Fatah Kashanchi¹^,5

¹Department of Biochemistry and Molecular Biology, George Washington University School of Medicine, Washington, DC 20037, USA

²Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA

³Institute for Genetic Medicine, Johns Hopkins Medical School, Baltimore, MD 21205, USA

⁴Institute of Signal Processing, Tampere University of Technology, PO Box 553, 33101, Tampere, Finland

⁵The Institute for Genomic Research, TIGR, Rockville, MD 20850, USA

author email corresponding author email* Contributed equally

Retrovirology 2005, 2:20doi:10.1186/1742-4690-2-20


Published:	21 March 2005

Abstract

Background

Despite the success of HAART, patients often stop treatment due to the inception of side effects. Furthermore, viral resistance often develops, making one or more of the drugs ineffective. Identification of novel targets for therapy that may not develop resistance is sorely needed. Therefore, to identify cellular proteins that may be up-regulated in HIV infection and play a role in infection, we analyzed the effects of Tat on cellular gene expression during various phases of the cell cycle.

Results

SOM and k-means clustering analyses revealed a dramatic alteration in transcriptional activity at the G1/S checkpoint. Tat regulates the expression of a variety of gene ontologies, including DNA-binding proteins, receptors, and membrane proteins. Using siRNA to knock down expression of several gene targets, we show that an Oct1/2 binding protein, an HIV Rev binding protein, cyclin A, and PPGB, a cathepsin that binds NA, are important for viral replication following induction from latency and de novo infection of PBMCs.

Conclusion

Based on exhaustive and stringent data analysis, we have compiled a list of gene products that may serve as potential therapeutic targets for the inhibition of HIV-1 replication. Several genes have been established as important for HIV-1 infection and replication, including Pou2AF1 (OBF-1), complement factor H related 3, CD4 receptor, ICAM-1, NA, and cyclin A1. There were also several genes whose role in relation to HIV-1 infection have not been established and may also be novel and efficacious therapeutic targets and thus necessitate further study. Importantly, targeting certain cellular protein kinases, receptors, membrane proteins, and/or cytokines/chemokines may result in adverse effects. If there is the presence of two or more proteins with similar functions, where only one protein is critical for HIV-1 transcription, and thus, targeted, we may decrease the chance of developing treatments with negative side effects.