HIV-1 expression induces tubular cell G2/M arrest and apoptosis.
Human renal biopsy studies suggest the presence of HIV-1 and associated signs of injury in renal tubular epithelial cells. Because renal epithelial cells lack conventional HIV-1 receptors, the modus operandi of HIV-1 in the induction of tubular cell injury remains a mystery. In the present study, we evaluated the role of HIV-1 gene expression in human proximal tubular cell apoptosis and cell cycle progression. HIV-1- or vector-transduced cells were assayed for cellular injury and cell cycle defect. HIV-1-transduced cells showed the progressive loss of viability in a time-dependent manner. Similarly, HIV-1-transduced cells showed greater apoptosis when compared with vector-transduced cells. A higher number of HIV-1 expressing cells showed cell cycle arrest at G2/M phase and enhanced tubular cell expression of phospho-p53(ser15), phospho-cdc-2(Tyr 15), and phospho-chk-2 (Thr 68). These findings suggest that in addition to the activation of apoptotic pathway, HIV-1-induced G2/M arrest may also contribute to tubular cell injury.
Vashistha
Himanshu
H
Immunology and Inflammation Center, Feinstein Institute for Medical Research, Manhasset, New York, USA.
Husain
Mohammad
M
Kumar
Dileep
D
Yadav
Anju
A
Arora
Shitij
S
Singhal
Pravin C
PC
D017209:Apoptosis / Q000235:genetics*; D002450:Cell Communication / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000473:pathology / Q000821:virology; D005434:Flow Cytometry; D016195:G2 Phase / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007684:Kidney Tubules / Q000473:pathology* / Q000821:virology*; D014161:Transduction, Genetic