Loss of neuronal integrity during progressive HIV-1 infection of humanized mice

Prasanta K. Dash, Santhi Gorantla, Howard E. Gendelman, Jaclyn Knibbe, George P. Casale, Edward Makarov, Adrian A. Epstein, Harris A. Gelbard, Michael D. Boska, Larisa Y. Poluektova

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Neuronal damage induced by ongoing human immunodeficiency virus type 1 (HIV-1) infection was investigated in humanized NOD/scid-IL- 2Rγcnull mice transplanted at birth with human CD34-positive hematopoietic stem cells. Mice infected at 5 months of age and followed for up to 15 weeks maintained significant plasma viral loads and showed reduced numbers of CD4+ T-cells. Prospective serial proton magnetic resonance spectroscopy tests showed selective reductions in cortical N-acetyl aspartate in infected animals. Diffusion tensor imaging revealed structural changes in cortical gray matter. Postmortem immunofluorescence brain tissue examinations for neuronal and glial markers, captured by multispectral imaging microscopy and quantified by morphometric and fluorescence emission, showed regional reduction of neuronal soma and synaptic architectures. This was evidenced by loss of microtubule-associated protein 2, synaptophysin, and neurofilament antigens. This study is the first, to our knowledge, demonstrating lost neuronal integrity after HIV-1 infection in humanized mice. As such, the model permits studies of the relationships between ongoing viral replication and virus-associated neurodegeneration.

Original languageEnglish (US)
Pages (from-to)3148-3157
Number of pages10
JournalJournal of Neuroscience
Volume31
Issue number9
DOIs
StatePublished - Mar 2 2011

ASJC Scopus subject areas

  • Neuroscience(all)

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