Mitochondrial DNA decline in T cells of HIV-1 seroconverters may be dependent on immune activation.
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.
Casula
Miriam
M
IATEC, Pietersbergweg 9, 1105 BM Amsterdam, The Netherlands. m.casula@iatec.com
Vrisekoop
Nienke
N
Wit
Ferdinand W
FW
de Baar
Michel P
MP
de Ronde
Anthony
A
Miedema
Frank
F
Reiss
Peter
P
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D004272:DNA, Mitochondrial / Q000032:analysis*; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008297:Male; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000821:virology
D004272:DNA, Mitochondrial