HIV-1 clade-specific differences in the induction of neuropathogenesis

Vasudev R. Rao, Andrew R. Sas, Eliseo A. Eugenin, Nagadenahalli B. Siddappa, Heather Bimonte-Nelson, Joan W. Berman, Udaykumar Ranga, William R. Tyor, Vinayaka R. Prasad

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Human immunodeficiency virus (HIV)-associated dementia (HAD) is common among clade B HIV-infected individuals, but less common and less severe among individuals infected with clade C HIV-1, suggesting clade-specific differences in neuropathogenicity. Although differences in neuropathogenicity have been investigated in vitro using viral proteins responsible for HAD, to date there are no virological studies using animal models to address this issue. Therefore, we investigated neuropathogenesis induced by HIV-1 clades using the severe combined immune deficiency (SCID) mouse HIV encephalitis model, which involves intracranial injection of macrophages infected with representative clade B (HIV-1ADA) or clade C (HIV-1Indie-C1) HIV-1 isolates into SCID mice. In cognitive tests, mice exposed to similar inputs of HIV-1 clade C made fewer memory errors than those exposed to HIV-1 clade B. Histopathological analysis of mice exposed to clade B exhibited greater astrogliosis and increased loss of neuronal network integrity. In vitro experiments revealed differences in a key characteristic of HIV-1 that influences HAD, increased monocyte infiltration. HIV-1Indie-C1-infected macrophages recruited monocytes poorly in vitro compared with HIV-1ADA-infected macrophages. Monocyte recruitment was HIV-1 Tat and CCL2 dependent. This is the first demonstration, ever since HIV neuropathogenesis was first recognized, that viral genetic differences between clades can affect disease severity and that such studies help identify key players in neuropathogenesis by HIV-1.

Original languageEnglish (US)
Pages (from-to)10010-10016
Number of pages7
JournalJournal of Neuroscience
Volume28
Issue number40
DOIs
StatePublished - Oct 1 2008

Keywords

  • Cognitive
  • Dementia
  • Human
  • Lentiviruses
  • Macrophage
  • Virus

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Rao, V. R., Sas, A. R., Eugenin, E. A., Siddappa, N. B., Bimonte-Nelson, H., Berman, J. W., Ranga, U., Tyor, W. R., & Prasad, V. R. (2008). HIV-1 clade-specific differences in the induction of neuropathogenesis. Journal of Neuroscience, 28(40), 10010-10016. https://doi.org/10.1523/JNEUROSCI.2955-08.2008