Abstract
Human immunodeficiency virus type 1 (HIV-1) central nervous system (CNS) infection in children is associated with impaired brain growth and neurodevelopmental delays. Neural progenitors are critical for neurogenesis. Human multipotential neural progenitors grown in culture are permissive for HIV-1 infection, but it is not known if infection of these cells occurs in vivo. Brain tissue from pre–highly active antiretroviral therapy (HAART) era pediatric acquired immunodeficiency syndrome (AIDS) patients was examined for evidence of HIV-1 infection of nestin-positive neural progenitors by in situ hybridization; or after laser microdissection harvest, DNA extraction, and polymerase chain reaction (PCR). HIV-1 or viral DNA was identified in nestin-positive cells in four of seven HIV-1–infected children, suggesting in vivo infection of neural progenitors.
This work was supported through the Intramural Research Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
The authors wish to thank and gratefully acknowledge the contributions of Ms. Linda Durham for her technical assistance, Mr. Peter Jensen for his technical guidance, Dr. Roma Chandra for identification of neural tissue obtained from the archives of the Department of Pathology, Children's National Medical Center, Washington, DC, Ms. Jean Hou for her editorial assistance, and Dr. Leslie Serchuck for her thoughtful review of the manuscript. The authors also acknowledge the contribution of Mr. Jim Nagle and the NINDS DNA sequencing facility staff, and the assistance of Mr. Rick Dreyfuss and Ms. Shauna Everett with image acquisition and photomicrography. Reagents obtained through the NIH AIDS Research and Reference Reagent program are so noted in this article.