Abstract

Pediatric HIV infection remains a global health crisis with a worldwide infection rate of 2.1 million (UNAIDS, 2013). Children are much more susceptible to HIV-1 neurological impairments than adults, which is exacerbated by co-infections. A main and obvious obstacle in pediatric HIV research is sample access. The proposed studies will take advantage of ongoing pediatric SIV pathogenesis and vaccine studies to maximize the use of nonhuman primate resources by expanding on the original pediatric SIV-related immunology studies to include quantitative neuropathology studies. We hypothesize that HIV infection in infants will induce neurodegeneration and impaired neurogenesis. Neonatal rhesus macaques (Macacca mulatta) that infected with SIVmac251 will be used to test this hypothesis. After a 6 to 33 week survival time, the animals were sacrificed for quantitative histopathological analysis.
AIM 1 will determine the extent of pediatric SIV-induced neurodegeneration in the hippocampus and fronto-limbic system and its relationship to viral loads.
In AIM 2 we will determine the mechanism(s) of pediatric SIV-induced neuronal loss in the hippocampus and fronto-limbic system. The goal of this project is to assess the impact of early HIV infection on the brain towards the long-term goal of evaluating treatment paradigms designed to protect the integrity of the developing brain from combined viral and bacterial infections through an interdisciplinary approach.

Public Health Relevance

Neurological impairment in pediatric HIV-1 represents a grave danger in resource-poor areas. This project aims at evaluating the neuropathology of pediatric SIV, so that treatment paradigms may be developed aimed at minimizing the deleterious effects of neonatal infection on long-term development.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Research Grants (R03)
Project #
5R03MH107261-02
Application #
9041037
Study Section
NeuroAIDS and other End-Organ Diseases Study Section (NAED)
Program Officer
Joseph, Jeymohan
Project Start
2015-04-01
Project End
2017-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
Howard University
Department
Physiology
Type
Schools of Medicine
DUNS #
056282296
City
Washington
State
DC
Country
United States
Zip Code
20059

  Publications

Carryl, Heather; Van Rompay, Koen K A; De Paris, Kristina et al. (2017) Hippocampal Neuronal Loss in Infant Macaques Orally Infected with Virulent Simian Immunodeficiency Virus (SIV). Brain Sci 7:
Carryl, Heather; Swang, Melanie; Lawrence, Jerome et al. (2015) Of mice and monkeys: can animal models be utilized to study neurological consequences of pediatric HIV-1 infection? ACS Chem Neurosci 6:1276-89