Renin modulates HIV replication in T cells

• Published in: Journal of leukocyte biology Vol. 96; no. 4; pp. 601 - 609
• Main Authors: Chandel, Nirupama, Ayasolla, Kamesh, Lan, Xiqian, Rai, Partab, Mikulak, Joanna, Husain, Mohammad, Malhotra, Ashwani, McGowan, Joseph, Singhal, Pravin C.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01-10-2014
• Subjects: Aspartyl protease; HIV-1 - drug effects; HIV-1 - physiology; Human immunodeficiency virus; Humans; Kruppel-Like Transcription Factors - metabolism; Models, Biological; NF-kappa B - metabolism; Promyelocytic Leukemia Zinc Finger Protein; Proteolysis - drug effects; Receptors, Cell Surface - deficiency; Receptors, Cell Surface - metabolism; Receptors, Signal Transduction, & Genes; Renin - metabolism; Renin - pharmacology; Signal Transduction; T-Lymphocytes - metabolism; T-Lymphocytes - virology; Vacuolar Proton-Translocating ATPases - deficiency; Vacuolar Proton-Translocating ATPases - metabolism; Virus Replication - drug effects; Vitamin D receptors; Aspartyl protease; Vitamin D receptors
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/JLB.2A0414-192R

Renin contributes to HIV replication in T cells via (P) RRPLZF signaling cascade and cleavage of Gag polyproteins.
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.