Restricted accessResearch articleFirst published online 2014-06
Genes Related to Antiviral Activity,Cell Migration,and Lysis Are Differentially Expressed in CD4 + T Cells in Human T Cell Leukemia Virus Type 1-Associated Myelopathy/Tropical Spastic Paraparesis Patients
Human T cell leukemia virus type 1 (HTLV-1) preferentially infects CD4+ T cells and these cells play a central role in HTLV-1 infection. In this study, we investigated the global gene expression profile of circulating CD4+ T cells from the distinct clinical status of HTLV-1-infected individuals in regard to TAX expression levels. CD4+ T cells were isolated from asymptomatic HTLV-1 carrier (HAC) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients in order to identify genes involved in HAM/TSP development using a microarray technique. Hierarchical clustering analysis showed that healthy control (CT) and HTLV-1-infected samples clustered separately. We also observed that the HAC and HAM/TSP groups clustered separately regardless of TAX expression. The gene expression profile of CD4+ T cells was compared among the CT, HAC, and HAM/TSP groups. The paxillin (Pxn), chemokine (C-X-C motif ) receptor 4 (Cxcr4), interleukin 27 (IL27), and granzyme A (Gzma) genes were differentially expressed between the HAC and HAM/TSP groups, regardless of TAX expression. The perforin 1 (Prf1) and forkhead box P3 (Foxp3) genes were increased in the HAM/TSP group and presented a positive correlation to the expression of TAX and the proviral load (PVL). The frequency of CD4+FOXP3+ regulatory T cells (Treg) was higher in HTLV-1-infected individuals. Foxp3 gene expression was positively correlated with cell lysis-related genes (Gzma, Gzmb, and Prf1). These findings suggest that CD4+ T cell activity is distinct between the HAC and HAM/TSP groups.
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