Hepatitis C virus core protein enhances HIV-1 replication in human macrophages through TLR2, JNK, and MEK1/2-dependent upregulation of TNF-α and IL-6

FEBS Lett. 2014 Sep 17;588(18):3501-10. doi: 10.1016/j.febslet.2014.08.009. Epub 2014 Aug 14.

Abstract

Despite their differential cell tropisms, HIV-1 and HCV dramatically influence disease progression in coinfected patients. Macrophages are important target cells of HIV-1. We hypothesized that secreted HCV core protein might modulate HIV-1 replication. We demonstrate that HCV core significantly enhances HIV-1 replication in human macrophages by upregulating TNF-α and IL-6 via TLR2-, JNK-, and MEK1/2-dependent pathways. Furthermore, we show that TNF-α and IL-6 secreted from HCV core-treated macrophages reactivates monocytic U1 cells latently infected with HIV-1. Our studies reveal a previously unrecognized role of HCV core by enhancing HIV-1 infection in macrophages.

Keywords: HIV-1; Hepatitis C virus core protein; Interleukin 6; MAPK kinase; Macrophages; Toll-like receptor 2; Tumor necrosis factor alpha.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Coinfection / virology
  • HEK293 Cells
  • HIV Infections / virology
  • HIV-1 / physiology*
  • Hepatitis C / virology
  • Humans
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism
  • MAP Kinase Kinase Kinases / metabolism
  • MAP Kinase Signaling System
  • Macrophages / virology*
  • Toll-Like Receptor 2 / metabolism
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation
  • Viral Core Proteins / physiology*
  • Virus Replication*

Substances

  • IL6 protein, human
  • Interleukin-6
  • TLR2 protein, human
  • TNF protein, human
  • Toll-Like Receptor 2
  • Tumor Necrosis Factor-alpha
  • Viral Core Proteins
  • nucleocapsid protein, Hepatitis C virus
  • MAP Kinase Kinase Kinases