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Related Concept Videos

Immunodeficiency Diseases01:25

Immunodeficiency Diseases

Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
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Peptide-based Identification of Functional Motifs and their Binding Partners
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Human immunodeficiency virus downregulates podocyte apoE expression.

Shitij Arora1, Mohammad Husain, Dileep Kumar

  • 1Immunology Center, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Medical Center, Manhasset, New York, USA.

American Journal of Physiology. Renal Physiology
|June 26, 2009
PubMed
Summary

Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) involves reduced apolipoprotein E (apoE) and perlecan in podocytes, potentially driven by the HIV nef gene, leading to mesangial cell proliferation.

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Area of Science:

  • Nephrology
  • Virology
  • Molecular Biology

Background:

  • Apolipoprotein E (apoE) is protective against mesangial cell injury.
  • Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is a significant complication of HIV infection.
  • The role of apoE in HIVAN pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the role of apoE and its downstream effects in HIVAN.
  • To determine the impact of HIV-1 infection and specific viral genes on apoE expression in podocytes.
  • To explore the association between apoE, perlecan, and mesangial cell proliferation in HIVAN.

Main Methods:

  • Comparison of renal cortical apoE expression in control and HIV-1 transgenic mice (Tg26).
  • In vitro studies using human and mouse podocytes transduced with HIV-1 constructs (NL4-3HIV, nef).
  • Microarray analysis to assess gene expression changes in nef-transduced podocytes.

Main Results:

  • HIV-1 transgenic mice (Tg26) exhibited decreased renal apoE and perlecan mRNA expression.
  • HIV-1 NL4-3 and HIV-1 nef gene transduction in podocytes reduced apoE expression.
  • Nef transduction led to significant downregulation of apoE and heparan sulfate (perlecan) mRNA.
  • Both Tg26 and nef transgenic mice showed mesangial cell proliferation.

Conclusions:

  • HIV-1 infection downregulates podocyte apoE expression.
  • The HIV-1 nef gene may be responsible for reducing apoE and perlecan expression.
  • Reduced apoE and perlecan may contribute to mesangial cell proliferation in HIVAN.