Mitochondrial changes associated with viral infectious diseases in the paediatric population

Abstract

Summary Infectious diseases occur worldwide with great frequency in both adults and children, causing 350,000 deaths in 2017, according to the latest World Health Organization reports. Both infections and their treatments trigger mitochondrial interactions at multiple levels: (i) incorporation of damaged or mutated proteins into the complexes of the electron transport chain; (ii) impact on mitochondrial genome (depletion, deletions and point mutations) and mitochondrial dynamics (fusion and fission); (iii) membrane potential impairment; (iv) apoptotic regulation; and (v) generation of reactive oxygen species, among others. Such alterations may result in serious adverse clinical events with considerable impact on the quality of life of the children and could even cause death. Herein, we use a systematic review to explore the association between mitochondrial alterations in paediatric infections including human immunodeficiency virus, cytomegalovirus, herpes viruses, various forms of hepatitis, adenovirus, T‐cell lymphotropic virus and influenza. We analyse how these paediatric viral infectious processes may cause mitochondrial deterioration in this especially vulnerable population, with consideration for the principal aspects of research and diagnosis leading to improved disease understanding, management and surveillance.

Antioxidant Therapeutic Strategies in Neurodegenerative Diseases

“…The human brain, typically 2% of normal body weight, receives 15% of the cardiac output and consumes approximately 20% of the total basal oxygen (O 2 − ) [ 2 ]. In line with the hypothesis of a mitochondrial basis in neurodegeneration, oxidative tissues with high energy demand are the most vulnerable to oxidative phosphorylation system (OXPHOS) defects [ 3 ]. Furthermore, the most metabolically active parts of the brain (the cortex, in particular the motor cortex and thalami, receiving three times the blood flow of white matter) are most vulnerable to hypoxic ischemic encephalopathy.…”

Assessment of mitochondrial toxicity in newborns and infants with congenital cytomegalovirus infection treated with valganciclovir

“…The rationale of the primary hypothesis of this study is that anti-CMV treatment with valganciclovir may be related to mitochondrial toxicity at a genetic and/or functional level mainly due to off-target inhibition of the mtDNA polymerase gamma. This assumption is based on a previous wide body of evidence reporting mtDNA depletion and mitochondrial dysfunction by other antiviral treatments, such as anti-HIV or anti-HCV NRTI therapies, 14 which present analogous mechanisms of action by blocking the viral DNA polymerases to avoid replication. NRTI-derived mitochondrial damage is not restricted to a specific level, but rather is generalised to the mitochondrial and functional levels.…”

“…Thus, secondary inhibition of this enzyme may cause point mutations, deletions and depletion (loss of an entire copy of the mitochondrial genome) in the mtDNA molecules. These alterations in the mitochondrial genome, which codes for proteins of the mitochondrial respiratory chain (MRC), can lead to mitochondrial dysfunction, ultimately compromising cell function, tissue viability and even the organism exposed,12–14 as described in previous literature in the case of NRTIs in vivo15–18 and in vitro 19 20. In fact, the range of clinical signs and symptoms that have been associated with mitochondrial dysfunction, of either congenital or acquired origin, is extensive and highly heterogeneous,21 with hearing loss being among the most relevant.…”