HIV-1 infection and the developing nervous system: Lineage-specific regulation of viral gene expression and replication in distinct neuronal precursors

Fabrizio Ensoli, Hong Wang, Valeria Fiorelli, Steven L. Zeichner, Maria Rita De Cristofaro, Giuseppe Luzi, Carol J. Thiele

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Neurologic abnormalities are common in HIV-1 infected patients and often represent the dominant clinical manifestation of pediatric AIDS. Although the neurological dysfunction has been directly related to CNS invasion by HIV-1, the pathogenesis of neurologic disorders remains unclear. Microglia and macrophages are major HIV-1 targets in the brain, whereas HIV-1 infected neurons or glial cells have been rarely reported. This suggests that indirect mechanisms may account for the severe neuronal damage observed in these patients. Nevertheless, immature, mitotically active neuronal and glial cells, which are present during fetal development, are susceptible to HIV-1 infection and replication in vitro, suggesting that HIV-1 infection during organ development may present unique features. To better characterize virus-host cells interactions in the developing CNS, we have examined the susceptibility of embryologically and biochemically distinct neuronal cell lines to HIV-1 infection. Here we show that mitotically active, immature neurons of distinct lineages, have different susceptibilities to HIV-1 infection and replication and different abilities to support viral gene expression. Mutational analysis of HIV-1 LTR reveals that a region of the viral promoter between nucleotide -255 to -166 is responsible for most quantitative and qualitative differences in viral transactivation among different neuroblasts. This suggests that specific regions of the viral promoter and cellular factors, either lineage- or differentiation-dependent, which bind to those regions, may contribute to control the levels of virus replication and possibly restrict the viral tropism in the developing brain. This may contribute to the establishment of a virus reservoir in the immature CNS and participate by either direct or indirect mechanisms to the severity of the AIDS-related pediatric neurological dysfunction.

Original languageEnglish
Pages (from-to)290-298
Number of pages9
JournalJournal of NeuroVirology
Volume3
Issue number4
Publication statusPublished - Aug 1997

Fingerprint

Viral Gene Expression Regulation
Nervous System
HIV Infections
HIV-1
Genetic Promoter Regions
Neuroglia
Acquired Immunodeficiency Syndrome
Viral Tropism
HIV Long Terminal Repeat
Pediatrics
Nervous System Malformations
Viruses
Neurons
Viral Genes
Brain
Microglia
Virus Replication
Fetal Development
Nervous System Diseases
Cell Communication

Keywords

  • CNS
  • Development cell cycle
  • Gene regulation
  • HIV-1
  • Pediatric aids

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology

Cite this

HIV-1 infection and the developing nervous system : Lineage-specific regulation of viral gene expression and replication in distinct neuronal precursors. / Ensoli, Fabrizio; Wang, Hong; Fiorelli, Valeria; Zeichner, Steven L.; De Cristofaro, Maria Rita; Luzi, Giuseppe; Thiele, Carol J.

In: Journal of NeuroVirology, Vol. 3, No. 4, 08.1997, p. 290-298.

Research output: Contribution to journalArticle

Ensoli, Fabrizio ; Wang, Hong ; Fiorelli, Valeria ; Zeichner, Steven L. ; De Cristofaro, Maria Rita ; Luzi, Giuseppe ; Thiele, Carol J. / HIV-1 infection and the developing nervous system : Lineage-specific regulation of viral gene expression and replication in distinct neuronal precursors. In: Journal of NeuroVirology. 1997 ; Vol. 3, No. 4. pp. 290-298.
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