Email updates

Keep up to date with the latest news and content from BMC Medical Genomics and BioMed Central.

Open Access Highly Accessed Research article

Genome-wide search for the genes accountable for the induced resistance to HIV-1 infection in activated CD4+ T cells: apparent transcriptional signatures, co-expression networks and possible cellular processes

Wen-Wen Xu13, Miao-Jun Han13, Dai Chen4, Ling Chen5, Yan Guo1, Andrew Willden6, Di-Qiu Liu1 and Hua-Tang Zhang12*

Author Affiliations

1 Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Jiaochang East Road 32, Kunming, Yunnan Province, 650223 China

2 Chongqing Center for Biomedical Research and Equipment Development, Chongqing Academy of Science and Technology, Chongqing, China

3 Graduate University of Chinese Academy of Sciences, Beijing, China

4 Novel Bioinformatics Co., Ltd, Shanghai, China

5 Yunnan centers for disease control and prevention, Kunming, China

6 Editorial Department, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China

For all author emails, please log on.

BMC Medical Genomics 2013, 6:15  doi:10.1186/1755-8794-6-15

Published: 1 May 2013

Abstract

Background

Upon co-stimulation with CD3/CD28 antibodies, activated CD4 + T cells were found to lose their susceptibility to HIV-1 infection, exhibiting an induced resistant phenotype. This rather unexpected phenomenon has been repeatedly confirmed but the underlying cell and molecular mechanisms are still unknown.

Methods

We first replicated the reported system using the specified Dynal beads with PHA/IL-2-stimulated and un-stimulated cells as controls. Genome-wide expression and analysis were then performed by using Agilent whole genome microarrays and established bioinformatics tools.

Results

We showed that following CD3/CD28 co-stimulation, a homogeneous population emerged with uniform expression of activation markers CD25 and CD69 as well as a memory marker CD45RO at high levels. These cells differentially expressed 7,824 genes when compared with the controls on microarrays. Series-Cluster analysis identified 6 distinct expression profiles containing 1,345 genes as the representative signatures in the permissive and resistant cells. Of them, 245 (101 potentially permissive and 144 potentially resistant) were significant in gene ontology categories related to immune response, cell adhesion and metabolism. Co-expression networks analysis identified 137 “key regulatory” genes (84 potentially permissive and 53 potentially resistant), holding hub positions in the gene interactions. By mapping these genes on KEGG pathways, the predominance of actin cytoskeleton functions, proteasomes, and cell cycle arrest in induced resistance emerged. We also revealed an entire set of previously unreported novel genes for further mining and functional validation.

Conclusions

This initial microarray study will stimulate renewed interest in exploring this system and open new avenues for research into HIV-1 susceptibility and its reversal in target cells, serving as a foundation for the development of novel therapeutic and clinical treatments.

Keywords:
HIV-1; Susceptibility; Resistance; CD4 + T cells; CD3/CD28 costimulation