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Renin modulates HIV replication in T cells.

Nirupama Chandel1, Kamesh Ayasolla1, Xiqian Lan1

  • 1Center of Immunology and Inflammation, Feinstein Institute for Medical Research, North Shore LIJ Hofstra Medical School, Manhasset, New York, USA; and.

Journal of Leukocyte Biology
|June 28, 2014
PubMed
Summary
This summary is machine-generated.

Human immunodeficiency virus (HIV) utilizes renin to boost its replication in T cells. Renin activates signaling pathways and cleaves viral proteins, promoting HIV spread.

Keywords:
Aspartyl proteaseVitamin D receptors

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Area of Science:

  • Virology
  • Immunology
  • Biochemistry

Background:

  • Human immunodeficiency virus (HIV) hijacks host cell machinery for replication.
  • Recent studies indicate HIV enhances renin expression in T cells (TCs).

Purpose of the Study:

  • To investigate the hypothesis that HIV induces and maintains high renin expression to promote its own replication in TCs.
  • To elucidate the molecular mechanisms by which renin influences HIV replication.

Main Methods:

  • Dose-response experiments assessing renin's effect on HIV replication in TCs.
  • Analysis of NF-κB activity and HIV replication in (P)RR-deficient or renin-deficient TCs.
  • Investigation of signaling pathways (e.g., (P)RR-PLZF, PI3K) activated by renin and Hpr.
  • Assessing the cleavage of angiotensinogen (Agt) and Gag polyproteins by renin and Hpr.
  • Evaluating the effect of aliskiren, a renin inhibitor, on these processes.

Main Results:

  • Renin significantly enhanced HIV replication in TCs in a dose-dependent manner.
  • TCs deficient in (P)RR or renin showed reduced NF-κB activity and HIV replication.
  • Renin and Hpr activated the (P)RR-PLZF signaling cascade and the PI3K pathway.
  • Both renin and Hpr cleaved Agt and HIV Gag polyproteins; aliskiren inhibited this cleavage.

Conclusions:

  • Renin plays a crucial role in promoting HIV replication within TCs.
  • Renin contributes to HIV replication via the (P)RR-PLZF signaling pathway and by cleaving Gag polyproteins.
  • Targeting renin may offer a novel therapeutic strategy against HIV infection.