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Human immunodeficiency virus type 1 Tat modulates proliferation and differentiation of human neural precursor cells: implication in NeuroAIDS

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Abstract

Human immunodeficiency virus type 1 (HIV-1) and viral proteins affect neuronal survival and neuron-glial cell interactions, which culminate in neurological disorders. HIV-1 infects regions of neurogenesis in human adult and pediatric brain. However, little is known about the effect of HIV-1 or viral proteins on the properties of human neural precursor cells (hNPCs), particularly neurogenesis, hence a detailed investigation on these lines is warranted. Human neural precursor cells were cultured in presence and absence of HIV-1B transactivating protein Tat to investigate if HIV-1 viral protein alters the properties of human neural precursor cells. Cellular and molecular approaches were adopted to study the effect of HIV-1B transactivating protein Tat on proliferation and differentiation potential of human fetal brain-derived NPCs. Cell proliferation assays such as BrdU and Ki67 staining and pathway-specific cDNA and protein arrays were used in the study. Data reveal that HIV-1B Tat protein severely affects proliferation of hNPCs, as evident by lower incorporation of BrdU and Ki67 staining as well as neurosphere assay. HIV-1 Tat substantially attenuated neurogenesis, as evident by the smaller numbers of Tuj-1- and doublecortin-positive cells differentiated from hNPCs, without affecting their viability. These data suggest that HIV-1 Tat alters the properties of human neural precursor cells via attenuation of the cell cycle regulatory unit cyclin D1 and the mitogen-activated protein kinase (MAPK) pathway, particularly extracellular signal-related kinase 1/2 (ERK1/2). The study provides new insights into cellular and molecular mechanisms that may modulate human neural precursor cell properties in HIV/AIDS (acquired immunodeficiency syndrome) individuals. Validation with autopsy brain samples is necessary to further substantiate these important observations.

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Authors and Affiliations

  1. PhD, NeuroAIDS Laboratory, Molecular and Cellular Neuroscience, National Brain Research Centre (NBRC), NH-8, Nainwal Mode, 122050, Manesar, Haryana, India

    Mamata Mishra, Manisha Taneja, Shaily Malik, Hena Khalique & Pankaj Seth

Authors
  1. Mamata Mishra
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  2. Manisha Taneja
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  3. Shaily Malik
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  4. Hena Khalique
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  5. Pankaj Seth
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Corresponding author

Correspondence to Pankaj Seth.

Additional information

Manisha Taneja and Shaily Malik have made equal contributions to this paper. This study was supported by research grants (BT/ PR6838/Med/14/881/2005 and BT/PR6615/Med/14/857/2005) from the Department of Biotechnology, Ministry of Science and Technology, India, to P.S., Senior Research Fellowship to M.M., Integrated MS-PhD Program Scholarship to S.M., and Project Assistantship to H.K. and M.T. from NBRC and DBT, India. The technical assistance from Mr. Durga Lal Meena and Mr. Naushad Alam during the study is greatly acknowledged. The authors thank Dr. Udaykumar Ranga for providing Tat B and Tat expression vectors.

This paper was first published online on Early Online on 14 September 2010.

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Mishra, M., Taneja, M., Malik, S. et al. Human immunodeficiency virus type 1 Tat modulates proliferation and differentiation of human neural precursor cells: implication in NeuroAIDS. Journal of NeuroVirology 16, 355–367 (2010). https://doi.org/10.3109/13550284.2010.513028

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  • DOI: https://doi.org/10.3109/13550284.2010.513028

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