Study of oxidative, enzymatic mitochondrial respiratory chain function and apoptosis in perinatally HIV-infected
Constanza Morén1, Glòria Garrabou, Antoni Noguera-Julian
1Mitochondrial Functionalism Laboratory, University of Barcelona, IDIBAPS, Hospital Clínic of Barcelona, Barcelona, Spain. cmoren1@clinic.ub.es
Insights
Mitochondrial dysfunction is evident in children with perinatally acquired human immunodeficiency virus (HIV), impacting oxygen consumption and respiratory chain activity. Both HIV infection and highly active antiretroviral therapy (HAART) contribute to this generalized mitochondrial impairment.
Area of Science:
- Cellular Biology
- Virology
- Pediatric Medicine
Background:
- Mitochondrial toxicity in perinatally human immunodeficiency virus (HIV)-infected children is understudied.
- Limited data exist on HIV or antiretroviral (ARV) drug-induced mitochondrial damage, including oxygen consumption and apoptosis, in this population.
- Understanding downstream effects of mitochondrial DNA depletion is crucial for perinatally HIV-infected pediatric patients.
Purpose of the Study:
- To investigate mitochondrial dysfunction in perinatally HIV-infected pediatric patients.
- To determine if mitochondrial DNA depletion is reflected in downstream cellular processes.
- To gain insight into the pathology of HIV and highly active antiretroviral therapy (HAART) in this cohort.
Main Methods:
- Studied 10 healthy controls and 20 perinatally HIV-infected children (10 on ARV treatment, 10 off treatment).
- Assessed mitochondrial mass, specific mitochondrial enzyme activities (Complex IV subunits II and IV), global and specific enzymatic/oxidative activities, and apoptosis.
- Analyzed peripheral blood mononuclear cells (PBMCs) for these parameters.
Main Results:
- Global oxygen consumption was significantly reduced in untreated HIV-infected patients compared to controls (P=0.014).
- Apoptosis showed a trend towards increase in untreated patients.
- Mitochondrial respiratory chain (MRC) activity (CI-III-IV) was significantly decreased in HAART-treated patients versus controls (P=0.02), with no significant difference between treated and untreated groups.
Conclusions:
- Both HIV infection and HAART play a pathogenic role in mitochondrial dysfunction in vertically infected children.
- Mitochondrial genome abnormalities appear to manifest as global alterations in the mitochondrial respiratory chain.
- Mitochondrial impairment associated with HIV and HAART is generalized in perinatally infected pediatric patients.
Abstract:
Mitochondrial toxicity in perinatally human immunodeficiency virus (HIV)-infected pediatric patients has been scarcely investigated. Limited data are available about HIV or antiretroviral (ARV)-mediated mitochondrial damage in this population group, specifically, regarding oxygen consumption and apoptosis approach. We aimed to elucidate whether a given mitochondrial DNA depletion is reflected at downstream levels, to gain insight on the pathology of HIV and highly active antiretroviral therapy (HAART) in perinatally HIV-infected pediatric patients. We studied 10 healthy control participants and 20 perinatally HIV-infected pediatric patients (10 under ARV treatment and 10 off treatment). We determined mitochondrial mass, subunits II and IV of complex IV, global and specific mitochondrial enzymatic and oxidative activities, and apoptosis from peripheral blood mononuclear cells. Global oxygen consumption was significantly compromised in HIV-infected untreated patients, compared to the control group (0.76 ± 0.01 versus 1.59 ± 0.15; P = 0.014). Apoptosis showed a trend to increase in untreated patients as well. The overall complex (C) CI-III-IV activity of the mitochondrial respiratory chain (MRC) was significantly decreased in HIV-infected treated patients with respect to the control group (1.52 ± 0.38 versus 6.38 ± 1.53; P = 0.02). No statistically significant differences were found between untreated and HAART-treated patients. These findings suggest the pathogenic role of both HIV and HAART in mitochondrial dysfunction in vertical infection. The abnormalities in mitochondrial genome may be downstream reflected through a global alteration of the MRC. Mitochondrial impairment associated with HIV and HAART was generalized, rather than localized, in this series of perinatally HIV-infected patients.
