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

Abstract

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.