Abstract
The neurological impact of Human Immunodeficiency Virus (HIV) on children includes loss of brain growth, motor abnormalities and cognitive dysfunction. Despite early antiretroviral treatment (ART) intervention to suppress viral load, neurological consequences of perinatal HIV-1 infection persist. Utilizing the pediatric simian immunodeficiency virus (SIV) infection model, we tested the hypothesis that early-life SIV infection depletes neuronal population in the hippocampus. A total of 22 ART-naïve infant rhesus macaques (Macaca mulatta) from previous studies were retrospectively analyzed. Infant macaques were either intravenously (IV) inoculated with highly virulent SIVmac251 at ~1 week of age and monitored for 6–10 weeks, or orally challenged with SIVmac251 from week 9 of age onwards with a monitoring period of 10–23 weeks post-infection (19–34 weeks of age), and SIV-uninfected controls were euthanized at 16–17 weeks of age. We have previously reported that the IV SIVmac251-infected neonatal macaques (Group 1) displayed a 42% neuronal reduction throughout the hippocampal cornu ammonis (CA) fields. The orally-infected infant macaques displayed a 75% neuronal reduction in the CA1 region compared to controls and 54% fewer neurons than IV SIV infants. The CA2 region showed a similar pattern, with a 67% reduction between orally-infected SIV subjects and controls and a 40% difference between IV-and orally-infected SIV groups. In the CA3 region, there were no significant differences between these groups, however both SIV-infected groups had significantly fewer pyramidal neurons than control subjects. There was no correlation between plasma viral load and neuronal populations in any of the CA fields. The loss of hippocampal neurons may contribute to the rapid neurocognitive decline associated with pediatric HIV infection. While each subfield showed vulnerability to SIV infection, the CA1 and CA2 subregions demonstrated a potentially enhanced vulnerability to pediatric SIV infection. These data underscore the need for early diagnosis and treatment, including therapeutics targeting the central nervous system (CNS).
Highlights
There are over 3.2 million children under the age of 15 currently living with human immunodeficiency virus (HIV), with an estimated one new diagnosis every 2 min [1,2].Brain Sci. 2017, 7, 40; doi:10.3390/brainsci7040040 www.mdpi.com/journal/brainsciBrain Sci. 2017, 7, 40Mother-to-child-transmission (MTCT) via pregnancy, delivery or breast-feeding accounts for15%–25% of new infections [3]
The loss of hippocampal neurons may contribute to the rapid neurocognitive decline associated with pediatric HIV infection
The infant rhesus macaques (Macacca mulatta) in those former studies were nursery-reared in pairs at the California National Primate Research Center (CNPRC) in accordance to American Association for Accreditation of Laboratory Animal Care Standards, with all protocols being approved by the UC Davis Institutional Animal Care and Use Committee
Summary
There are over 3.2 million children under the age of 15 currently living with human immunodeficiency virus (HIV), with an estimated one new diagnosis every 2 min [1,2].Brain Sci. 2017, 7, 40; doi:10.3390/brainsci7040040 www.mdpi.com/journal/brainsciBrain Sci. 2017, 7, 40Mother-to-child-transmission (MTCT) via pregnancy, delivery or breast-feeding accounts for15%–25% of new infections [3]. Brain Sci. 2017, 7, 40; doi:10.3390/brainsci7040040 www.mdpi.com/journal/brainsci. 15%–25% of new infections [3]. In the United States, less than 200 babies are infected with HIV annually, due to the use of ART and the avoidance of breastfeeding [4]. In under-resourced parts of the world (e.g., Sub-Saharan Africa), ART access still varies widely from country to country [5], and exclusive breastfeeding is necessary to reduce the risk of mortality due to malnutrition or non-HIV-1 illnesses such as respiratory infections and diarrhea [6,7,8]. About 15% of HIV MTCT cases occur as a result of breastfeeding [3]
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