HIV-1-infected long-term non-progressors have milder mitochondrial impairment and lower mitochondrially-driven apoptosis in peripheral blood mononuclear cells than typical progressors.
Mitochondrial parameters in peripheral blood mononuclear cells (PBMC) and their relationship with mitochondrially-driven PBMC apoptosis were investigated in a group of HIV-1-infected long-term nonprogressors (LTNP) and compared with untreated asymptomatic HIV-1 infected typical progressors (TP) and uninfected healthy controls (HC). Twenty-six LTNP, 27 TP and 31 HC were evaluated. Studies were performed in PBMCs. Mitochondrial DNA content (mtDNA) was assessed by quantitative real-time PCR. Activities of mitochondrial respiratory chain complexes (MRC) II, III and IV were determined by spectrophotometry. Caspase-3 activity was assessed by fluorimetry, and caspase-9 activation and Bcl-2 levels were assessed by immunoblotting. mtDNA abundance (p<0.05), MRC complex II (p<0.001), complex III (p<0.01) and complex IV (p=0.01) were lower in the TP group than in the HC group. In the LTNP group these parameters were similar to those of the HC group except for complex II, which was decreased (p<0.01). The PBMC of TP showed the highest overall apoptotic activation, since their caspase-3 activity was greater than that of HC (p<0.05) and LTNP. In the case of LTNP, however, the difference was non-significant. Caspase-9 and the caspase-9/Bcl-2 ratio were both over-expressed in TP compared to HC (p<0.01) and LTNP (p<0.05). Both of these measurements indicate that mitochondrially-driven apoptosis in TP is greater than in LTNP and HC. A relationship between mitochondrial damage and apoptotic activation was found in TP. Mitochondrial damage is associated with increased PBMC apoptosis in patients with active HIV-1 replication (TP). These abnormalities are slight or not present in LTNP.
Peraire
Joaquim
J
Hospital Universitari de Tarragona Joan XXIII, Universitat Rovira i Virgili, Tarragona, Spain.
Miró
Oscar
O
Saumoy
Maria
M
Domingo
Pere
P
Pedrol
Enric
E
Villarroya
Francesc
F
Martínez
Esteban
E
López-Dupla
Miguel
M
Garrabou
Glória
G
Sambeat
M Antònia
MA
Deig
Elisabet
E
Villarroya
Joan
J
Chacón
Matilde R
MR
López
Sònia
S
Fontanet
Angels
A
Holmstrom
Maija
M
Giralt
Marta
M
Gatell
Josep M
JM
Vidal
Francesc
F
D000328:Adult; D017209:Apoptosis; D053148:Caspase 3 / Q000032:analysis; D053453:Caspase 9 / Q000032:analysis; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000032:analysis; D042963:Electron Transport Complex II / Q000032:analysis / Q000378:metabolism; D014450:Electron Transport Complex III / Q000032:analysis / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000032:analysis / Q000378:metabolism; D005260:Female; D005470:Fluorometry; D015658:HIV Infections / Q000473:pathology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000254:growth & development; D006801:Humans; D015151:Immunoblotting; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000166:cytology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction / Q000379:methods; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013053:Spectrophotometry
D004272:DNA, Mitochondrial; D019253:Proto-Oncogene Proteins c-bcl-2; C478189:respiratory complex II; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; D053148:Caspase 3; D053453:Caspase 9; D014450:Electron Transport Complex III