HIV-associated nephropathy (HIVAN) is an important complication of acquired immunodeficiency syndrome (AIDS).Its manifestation requires presence of specific ancestry (APOL1 gene), environmental (HIV infection), and host factors. Although significant research has been done to identify and to delineate the involved genes to correlate with the ancestry but there has been a limited effort to identify subversive activities o HIV, which might be contributing to specific host factors- increased expression of Snail- required for the display of unique phenotype of renal lesions in HIVAN. In preliminary studies, we found that HIV enhanced renal cell expression of Snail (a repressor of E-cadherin transcriptor, and a promoter of proliferative phenotype). Since Snail has been demonstrated to repress transcription of vitamin D receptor (VDR) and nephrin (a podocyte slit diaphragm protein), it carries a potential to alter renal cell phenotype. HIV is known to modulate gene expression by DNA methylation (epigenetic factors). In our laboratory, we observed that both glomerular and tubular epithelial cells in HIVAN mice displayed enhanced expression of Snail and diminished expression of VDR and nephrin. On the basis of these findings we will test the following hypotheses * HIV alters renal cell gene expression through the induction of epigenetic factors * Renal cortical sections of HIVAN mice as well as HIVAN patients would display enhanced Snail expression and diminished expression of E/P-cadherin, VDR, and nephrin * Inhibition of either HIV-induced epigenetic factors, associated downstream signaling, or both would not only attenuate the development of HIVAN phenotype but will also prevent, retard the progression, and/or cause resolution of HIVAN We suggest that testing of these hypotheses will aid in developing therapeutic strategies to prevent, retard the progression, or cause resolution of HIVAN.

Public Health Relevance

HIV-associated nephropathy (HIVAN) is the third leading cause of End-stage renal disease among individuals with African American background, and is associated with the highest rates of hospitalizations in this population. In preliminary studies, w observed that HIV-induced subversion modulated expression of genes which maintain kidney cell phenotypes. We hypothesize that HIV-induced epigenetic factors are playing as the host factors for the initiation as well as progression of HIVAN.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
NeuroAIDS and other End-Organ Diseases Study Section (NAED)
Program Officer
Kimmel, Paul
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Feinstein Institute for Medical Research
United States
Zip Code
Chandel, Nirupama; Ayasolla, Kamesh; Wen, Hongxiu et al. (2017) Vitamin D receptor deficit induces activation of renin angiotensin system via SIRT1 modulation in podocytes. Exp Mol Pathol 102:97-105
Lan, Xiqian; Wen, Hongxiu; Cheng, Kang et al. (2017) Hedgehog pathway plays a vital role in HIV-induced epithelial-mesenchymal transition of podocyte. Exp Cell Res 352:193-201
Mikulak, Joanna; Oriolo, Ferdinando; Portale, Federica et al. (2016) Impact of APOL1 polymorphism and IL-1? priming in the entry and persistence of HIV-1 in human podocytes. Retrovirology 13:63
Haque, Shabirul; Lan, Xiqian; Wen, Hongxiu et al. (2016) HIV Promotes NLRP3 Inflammasome Complex Activation in Murine HIV-Associated Nephropathy. Am J Pathol 186:347-58
Khatua, Atanu K; Cheatham, Amber M; Kruzel, Etty D et al. (2015) Exon 4-encoded sequence is a major determinant of cytotoxicity of apolipoprotein L1. Am J Physiol Cell Physiol 309:C22-37
Singh, Tejinder; Ayasolla, Kamesh; Rai, Partab et al. (2015) AT1R blockade in adverse milieus: role of SMRT and corepressor complexes. Am J Physiol Renal Physiol 309:F189-203
Chandel, Nirupama; Ayasolla, Kameshwar S; Lan, Xiqian et al. (2015) Epigenetic Modulation of Human Podocyte Vitamin D Receptor in HIV Milieu. J Mol Biol 427:3201-15
Ayasolla, Kamesh R; Rai, Partab; Rahimipour, Shai et al. (2015) Tubular cell phenotype in HIV-associated nephropathy: role of phospholipid lysophosphatidic acid. Exp Mol Pathol 99:109-15
Lan, Xiqian; Wen, Hongxiu; Saleem, Moin A et al. (2015) Vascular smooth muscle cells contribute to APOL1-induced podocyte injury in HIV milieu. Exp Mol Pathol 98:491-501
Lan, Xiqian; Wen, Hongxiu; Lederman, Rivka et al. (2015) Protein domains of APOL1 and its risk variants. Exp Mol Pathol 99:139-44

Showing the most recent 10 out of 22 publications