title: Human immunodeficiency virus type 1 Tat modulates proliferation and differentiation of human neural precursor cells: implication in NeuroAIDS.
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.
authors.affiliation: Molecular and Cellular Neuroscience, National Brain Research Center, Manesar, Haryana, India.
authors.forename: Mamata
authors.initials: M
authors.lastname: Mishra
authors.forename: Manisha
authors.initials: M
authors.lastname: Taneja
authors.forename: Shaily
authors.initials: S
authors.lastname: Malik
authors.forename: Hena
authors.initials: H
authors.lastname: Khalique
authors.forename: Pankaj
authors.initials: P
authors.lastname: Seth
mesh_terms: D015526:AIDS Dementia Complex / Q000473:pathology / Q000821:virology*; D001921:Brain / Q000473:pathology / Q000821:virology; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D015536:Down-Regulation; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology* / Q000821:virology*; D055495:Neurogenesis; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D019938:Cyclin D1