Mitochondrial DNA decline in T cells of HIV-1 seroconverters may be dependent on immune activation

Abstract

BACKGROUND: Earlier reports have indicated that human immunodeficiency virus type 1 (HIV-1) infection itself might cause mitochondrial DNA (mtDNA) decline in peripheral blood mononuclear cells (PBMCs). However, the mtDNA dynamics within this heterogeneous cell population during HIV-1 infection are not fully understood. METHODS: mtDNA content was assessed longitudinally in PBMCs and in isolated CD4(+) and CD8(+) T cells from 16 documented HIV-1 seroconverters who were naive to antiretroviral therapy. The correlation between the mtDNA content of CD4(+) and CD8(+) T cells and their immunologically activated proportion was studied. Additionally, mtDNA content was measured within isolated activated and nonactivated CD4(+) and CD8(+) T cells obtained from 5 antiretroviral-naive men with chronic HIV-1 infection. RESULTS: In the seroconverter group, mtDNA content in CD8(+) T cells decreased 5 years after seroconversion (P=.007). mtDNA content in either CD4(+) or CD8(+) T cells did not correlate with the proportion of activated cells within either population. However, for the chronically infected men, mtDNA content in activated CD8(+) T cells was lower than that in nonactivated cells (P=.043). A similar trend was observed in the CD4(+) T cell fraction. CONCLUSIONS: These findings indicate that HIV-1 infection affects mtDNA content, particularly in the most immunologically activated cells. Furthermore, the importance of measuring mtDNA in specific cell fractions rather than in the heterogeneous PBMC population is emphasized.