Identification of a host gene subset related to disease prognosis of HIV-1 infected individuals.

Although plasma-virus-RNA level and CD4-positive-T-cell count are useful to monitor clinical status of the human immunodeficiency virus (HIV)-infected individuals, clinical course is often varied among patients and sometimes difficult to predict. To identify additional parameters associated with disease progression, we examined by cDNA microarray the expression profiles of 731 immune-response-related genes in the peripheral blood mononuclear cells (PBMCs) from 21 HIV-positive individuals in Uganda. The analysis enabled the patients to be classified into three distinct groups on the basis of the gene expression patterns. Notably, these groups, clusters I, II and III, were highly associated with clinical status of the patients defined by CDC classification, categories A, B, and C, respectively. Statistical analysis identified 40 genes whose expressions were significantly up- or down-regulated in the cluster III patients (p<0.05). Up- and down-regulated genes included ones involved in immature T lymphocytes differentiation, apoptosis signaling, and active HIV replication, suggesting that the levels of active destruction and regeneration of mature T lymphocytes associated with enhanced HIV-1 replication is related to the disease progression. Follow-up study showed that the cluster classification improved prediction of disease prognosis with the CDC classification. These findings provide new clues for studying perturbation of host immunity, pathogenesis, and disease prognosis of HIV-infected individuals.

[1]  P. Brandtzaeg,et al.  Age‐Related Changes in CCR9+ Circulating Lymphocytes: Are CCR9+ Naive T Cells Recent Thymic Emigrants? , 2001, Scandinavian journal of immunology.

[2]  G. Marone,et al.  Tat Protein Is an HIV-1-Encoded β-Chemokine Homolog That Promotes Migration and Up-Regulates CCR3 Expression on Human FcεRI+ Cells1 , 2000, The Journal of Immunology.

[3]  H. Ullum,et al.  Impaired production of cytokines is an independent predictor of mortality in HIV-1-infected patients , 2003, AIDS.

[4]  M. Brenner,et al.  MHC class I-like, class II-like and CD1 molecules: distinct roles in immunity. , 1995, Immunology today.

[5]  Y. Chen,et al.  Nuclear translocation of PDCD5 (TFAR19): an early signal for apoptosis? , 2001, FEBS letters.

[6]  R. Ashmun,et al.  Molecular cloning, expression, and chromosomal localization of a human gene encoding the CD33 myeloid differentiation antigen. , 1988, Blood.

[7]  R. Warnke,et al.  A unique antigen on mature B cells defined by a monoclonal antibody. , 1986, Journal of immunology.

[8]  M. Zeitz,et al.  HIV‐1 p24 but not proviral load is increased in the intestinal mucosa compared with the peripheral blood in HIV‐infected patients , 1998, AIDS.

[9]  K. Matsushima,et al.  Comprehensive gene expression profile of human activated T(h)1- and T(h)2-polarized cells. , 2001, International immunology.

[10]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Yudong D. He,et al.  Gene expression profiling predicts clinical outcome of breast cancer , 2002, Nature.

[12]  Jane W. Segebrecht,et al.  Microarray analysis of cytokine and chemokine genes in the brains of macaques with SHIV‐encephalitis , 2003, Journal of medical primatology.

[13]  E. Lander,et al.  A molecular signature of metastasis in primary solid tumors , 2003, Nature Genetics.

[14]  J. Karn,et al.  Human immunodeficiency virus type-1 Tat is an integral component of the activated transcription-elongation complex. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Mesirov,et al.  Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. , 1999, Science.

[16]  Analysis of mRNA with microsomal fractionation using a SAGE-based DNA microarray system facilitates identification of the genes encoding secretory proteins. , 2003, Genome research.

[17]  S. Dandekar,et al.  Gastrointestinal T Lymphocytes Retain High Potential for Cytokine Responses but Have Severe CD4+ T-Cell Depletion at All Stages of Simian Immunodeficiency Virus Infection Compared to Peripheral Lymphocytes , 1998, Journal of Virology.

[18]  J. Carlis,et al.  Functional genomic analysis of the response of HIV-1-infected lymphatic tissue to antiretroviral therapy. , 2004, The Journal of infectious diseases.

[19]  N. Pantazis,et al.  Elevated serum levels of soluble immune activation markers are associated with increased risk for death in HAART-naive HIV-1-infected patients. , 2003, AIDS patient care and STDs.

[20]  Roger E Bumgarner,et al.  Large-scale monitoring of host cell gene expression during HIV-1 infection using cDNA microarrays. , 2000, Virology.

[21]  B. Haynes,et al.  Identification and characterization of a 100-kD ligand for CD6 on human thymic epithelial cells , 1995, The Journal of experimental medicine.