title: Renin modulates HIV replication in T cells.
abstract: HIV is known to subvert cellular machinery to enhance its replication. Recently, HIV has been reported to enhance TC renin expression. We hypothesized that HIV induces and maintains high renin expression to promote its own replication in TCs. Renin enhanced HIV replication in TCs in a dose-dependent manner. (P)RR-deficient TCs, as well as those lacking renin, displayed attenuated NF-κB activity and HIV replication. TCs treated with renin and Hpr displayed activation of the (P)RR-PLZF protein signaling cascade. Renin, HIV, and Hpr activated the PI3K pathway. Both renin and Hpr cleaved Agt (a renin substrate) to Ang I and also cleaved Gag polyproteins (protease substrate) to p24. Furthermore, aliskiren, a renin inhibitor, reduced renin- and Hpr-induced cleavage of Agt and Gag polyproteins. These findings indicate that renin contributes to HIV replication in TCs via the (P)RR-PLZF signaling cascade and through cleavage of the Gag polyproteins.
authors: Center of Immunology and Inflammation, Feinstein Institute for Medical Research, North Shore LIJ Hofstra Medical School, Manhasset, New York, USA; and.
authors: Nirupama
authors: N
authors: Chandel
authors: Center of Immunology and Inflammation, Feinstein Institute for Medical Research, North Shore LIJ Hofstra Medical School, Manhasset, New York, USA; and.
authors: Kamesh
authors: K
authors: Ayasolla
authors: Center of Immunology and Inflammation, Feinstein Institute for Medical Research, North Shore LIJ Hofstra Medical School, Manhasset, New York, USA; and.
authors: Xiqian
authors: X
authors: Lan
authors: Center of Immunology and Inflammation, Feinstein Institute for Medical Research, North Shore LIJ Hofstra Medical School, Manhasset, New York, USA; and.
authors: Partab
authors: P
authors: Rai
authors: Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: Joanna
authors: J
authors: Mikulak
authors: Center of Immunology and Inflammation, Feinstein Institute for Medical Research, North Shore LIJ Hofstra Medical School, Manhasset, New York, USA; and.
authors: Mohammad
authors: M
authors: Husain
authors: Center of Immunology and Inflammation, Feinstein Institute for Medical Research, North Shore LIJ Hofstra Medical School, Manhasset, New York, USA; and.
authors: Ashwani
authors: A
authors: Malhotra
authors: Center of Immunology and Inflammation, Feinstein Institute for Medical Research, North Shore LIJ Hofstra Medical School, Manhasset, New York, USA; and.
authors: Joseph
authors: J
authors: McGowan
authors: Center of Immunology and Inflammation, Feinstein Institute for Medical Research, North Shore LIJ Hofstra Medical School, Manhasset, New York, USA; and psinghal@nshs.edu.
authors: Pravin C
authors: PC
authors: Singhal
mesh_terms: D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D059748:Proteolysis / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000378:metabolism; D012083:Renin / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology*; D025262:Vacuolar Proton-Translocating ATPases / Q000172:deficiency / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*; D000093342:Prorenin Receptor
chemical_list: D051741:Kruppel-Like Transcription Factors; D016328:NF-kappa B; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011956:Receptors, Cell Surface; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor; C092037:ZBTB16 protein, human
keywords: Aspartyl protease; Vitamin D receptors