Impact of APOL1 polymorphism and IL-1β priming in the entry and persistence of HIV-1 in human podocytes

Retrovirology. 2016 Sep 6;13(1):63. doi: 10.1186/s12977-016-0296-3.


Background: Patients of African ancestry with untreated HIV-1 infection and carrying the G1 or G2 kidney disease risk variants (Vs) at the APOL1 gene have a tenfold higher risk of developing HIV-associated nephropathy (HIVAN) compared to those with the non-risk wild type (WT) G0 variant. However, the mechanistic contribution of the APOL1 allelic state to kidney injury in HIV-1 infection remains to be elucidated.

Results: Non-risk WT APOL1 is associated with lower intracellular levels of HIV-1 in conditionally immortalized human podocytes, while the over expression of G1 or G2 risk Vs significantly increases viral accumulation. The priming of podocytes with exogenous IL-1β facilitates HIV-1 entry, via the up-regulation of DC-SIGN. The over expression of APOL1 G1 and G2 risk Vs in combination with an increase in IL-1β levels causes a greater increase in viral concentration than either condition alone. In turn, HIV-1 and exogenous IL-1β together induce a de novo secretion of endogenous IL-1β and an increase of APOL1 gene expression.

Conclusions: Our findings indicate that the presence of risk Vs of APOL1 is permissive of HIV-1 persistence in human podocytes in synergy with IL-1β, a cytokine that characterizes the inflammatory milieu of acute and chronic phases of HIV-1 infection. The elucidation of these molecular mechanisms explains, at least in part, the higher frequency of HIVAN in populations carrying the risk polymorphic genetic variant of APOL1 gene.

Keywords: APOL1; DC-SIGN; HIV-1; HIVAN; IL-1β; Podocyte.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS-Associated Nephropathy / genetics*
  • AIDS-Associated Nephropathy / immunology
  • AIDS-Associated Nephropathy / virology
  • Africa
  • Alleles
  • Apolipoprotein L1
  • Apolipoproteins / genetics*
  • Cell Adhesion Molecules / genetics
  • Female
  • Genetic Predisposition to Disease / ethnology
  • HIV Infections / ethnology
  • HIV Infections / genetics*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / physiology*
  • Humans
  • Interleukin-1beta / biosynthesis
  • Interleukin-1beta / immunology*
  • Lectins, C-Type / genetics
  • Lipoproteins, HDL / genetics*
  • Male
  • Middle Aged
  • Podocytes / virology*
  • Polymorphism, Genetic*
  • Receptors, Cell Surface / genetics
  • Virus Internalization


  • APOL1 protein, human
  • Apolipoprotein L1
  • Apolipoproteins
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Interleukin-1beta
  • Lectins, C-Type
  • Lipoproteins, HDL
  • Receptors, Cell Surface